The Frontiers of Inorganic Chemistry 2002jtchen/20030926_Frontiers...2003/09/26 · the ways in which Inorganic Chemistry plays a major role in all aspects of modern life. A summary

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The Frontiers of Inorganic Chemistry

2002

A report based on the workshop sponsored by the National Science Foundation

Held at Copper Mountain, Colorado September 8-10, 2001

Hilary Arnold Godwin, P.I. Brian Hoffman, co-P.I.

Kristin Bowman-James, co-P.I.

Last modified February 17, 2003

Report from the Frontiers of Inorganic Chemistry Workshop 2002

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Table of Contents

Chapter 1: Overview and Summary…………………………………………………………….…1 Chapter 2: Detailed Report on Core Topics……………………………………………………...13 Chapter 3: Detailed Report on Materials Inorganic Chemistry…………………...………...…...17 Chapter 4: Detailed Report on Catalysis….……………………………………………………...24 Chapter 5: Detailed Report on Bioinorganic Chemistry…………………….…………………...40 Chapter 6: Detailed Report on Chemistry on New Length Scales…………..…………………...59 Chapter 7: Detailed Report on Environmental Inorganic Chemistry……………..……………...67 Chapter 8: Possible Educational Uses For This Report……………..…………….......................80 Appendix I: Detailed Schedule of Workshop……………………………………………….…...81 Appendix II: List of Workshop Participants……………………..……………………….……...85 Appendix III: Table of Contributions and Advances in Inorganic Chemistry……..…….………87 Appendix IV: Table of Frontier Topics in Inorganic Chemistry………………..……….………89 Appendix V: Evaluation of Workshop by Participants………..…………………..…….………94 Appendix VI: Summary of Workshop Expenses…….………..…………………..…….……..105


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Chapter 1 – Overview and Summary I. INTRODUCTION From the clothes we wear to the diseases we battle, Inorganic Chemistry plays a central role in understanding our world and improving our lives. The “Frontiers in Inorganic Chemistry Workshop,” held at Copper Mountain, Colorado, on September 8-10, 2001, was organized to chart the ways in which this discipline is growing in scientific scope and societal impact. The Workshop discussions highlighted key contributions of Inorganic Chemistry in the past and identified numerous specific ways in which both the scope and impact of Inorganic Chemistry will increase explosively in the coming decades. This report begins with a section describing the genesis and organization of the Workshop, its charge, its makeup, and its goals (Chapter 1, Section II). For organizational purposes, the discipline was divided into the six Thematic Areas (Table 1.1) at the meeting, because each Area has its own challenges and methodologies. Dividing the community into these Areas hides a commonality of methodology and approach that links all areas of Inorganic Chemistry and the extent to which Inorganic Chemistry pervades other disciplines. Indeed, there was a lively debate at the workshop over a proposal that the report be titled “Inorganic Chemistry and Life,” a phrase that serves both to elicit and challenge the reaction, “That’s an oxymoron: life is organic not inorganic.” Although the title was not adopted, through their discussion of the highlights and frontiers of the discipline, the participants clearly articulated the ways in which Inorganic Chemistry plays a major role in all aspects of modern life. A summary of the deliberations for the six Thematic Areas is contained in the next section of the report (Chapter 1, Section III). In addition, the full reports from the six Thematic Areas are provided in Chapters 2-7. For each Area, a summary is provided of both highlights of key past accomplishments and “frontier” topics that are of central importance now. Topics were considered “frontiers” if the participants felt that they would continue to be important in the coming decade; newly emerging topics of clear future importance were also included. The discussions in each Area addressed two additional issues of importance in the pursuit of research in Inorganic Chemistry. The first issue is, what is the proper balance between single-investigator and multi-investigator funding mechanisms? On the whole, the Workshop participants responded that although cross-discipline collaborations are very often of great benefit, their existence in Inorganic Chemistry typically is not linked to joint funding of collaborators. The second 'issue' is the possibility of a tension between so-called “fundamental” research and “applied/directed” research; the participants typically viewed this as a false dichotomy. Discussions of these issues are presented in Chapter 1, Section IV. Finally, although not a central focus of the Workshop, remarks are made in the Area reports about the education of students through doctoral and postdoctoral research in Inorganic Chemistry, and indeed the possible use of this report as an educational tool. Possible


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approaches are discussed in Chapter 8. II. NATURE OF WORKSHOP The primary goal of the Frontiers of Inorganic Chemistry Workshop was to bring together a small group of inorganic chemists under the auspices of the Division of Chemistry of the National Science Foundation, to develop a mission statement for the development of Inorganic Chemistry over the next decade. This agenda contrasts with that of other NSF sponsored workshops in Inorganic Chemistry (e.g. the 2000 NSF Inorganic Workshop, http://stanley.chem.lsu.edu/NSF-workshop.htm, or the Inorganic Biochemistry Summer Workshop, http://www.uga.edu/cms/IBSW.html), which primarily focused on presentation of recent results or graduate and postdoctoral training. The Frontiers workshop was designed to bring to the forefront a discussion of the following issues:

• What are the important accomplishments, and the current and future frontiers for Inorganic Chemistry

• How can we best balance the desire for specific scientific advances with the fundamental and ongoing need for non-directed basic research?

• What balance between multi-investigator vs. single-investigator grants would most effectively promote new discoveries in Inorganic Chemistry?

To promote facile discussion of these issues, the workshop format involved breakout sessions (see Appendix I for detailed program) into small working groups of four to six participants, which focused on the thematic areas in Inorganic Chemistry listed in Table 1.1. Table 1.1 Thematic Areas Core Topics Materials Inorganic Chemistry Catalysis Bioinorganic Chemistry Chemistry on New Length Scales Environmental Inorganic Chemistry Following the breakout sessions, each working group then provided a summary of their discussion to the entire group in a panel discussion. These summaries were then used to compile the reports for the individual groups (Chapters 2-7). The breakout group/discussion format employed for the workshop necessarily required that the workshop attendance be limited to a small number (~30-40) of individuals. The individuals invited to attend the workshop were selected based on suggestions from the organizing committee and group leaders, as well as NSF staff. The participants were selected so that they would represent not only a broad range of research areas, but also reflect the diversity of the scientific community with respect to gender, race, age, geographic location, and type of institution. A total of 28 professors (see Appendix II for complete list of workshop attendees) who conduct research in Inorganic Chemistry (broadly defined) and one graduate assistant (John Magyar, Northwestern University), who assisted the organizing committee with organizational matters, attended the workshop as paid participants. In


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addition, four representatives from the National Science Foundation (Donald Burland, Michael Clarke, Katharine Covert, and John Gilje) and one representative from the Department of Energy (Raoul Miranda) attended the meeting. III. FRONTIERS OF INORGANIC CHEMISTRY: SUMMARY OF THE REPORTS FROM THE THEMATIC AREAS A. Past Highlights of Inorganic Chemistry Each thematic group was asked to begin their discussion by articulating the most important contributions that their Area of Inorganic Chemistry has made in the past to our collective intellectual endeavor. These are summarized below for each Area. Highlights of these contributions are listed in Appendix III. The full record of the discussions in each Area is presented in Chapters 2-7. Taken together, these contributions clearly point not only to the pivotal role that Inorganic Chemistry plays in our understanding of basic chemical phenomena, but also to the contributions that IC makes to other scientific fields. 1. Past Highlights in Core Topics Contributions to the “core” of inorganic chemistry are, by definition, those that fundamentally change the way we think about inorganic chemistry. Examples of significant discoveries and developments that have resulted in paradigm shifts in inorganic chemistry include:

• Weakly coordinating anions • Enantiomorphic site control in single-site Ziegler-Natta catalysis • Fixed-distance electron transfer • Metal-metal multiple bonding in molecular systems • Frontier molecular orbital theory of organometallic reactions

2. Past Highlights in Materials Inorganic Chemistry Contributions in the field of materials inorganic chemistry are typically judged by either their utility in chemical industry or their impact on fundamental research. An example of the former is the development of new zeolites (e.g., ZSM5), which are used for a number of industrial processes, including hydrocarbon cracking. An example of the latter is the discovery of high temperature superconducting copper oxides (e.g., YBa2Cu3O7), which spawned renewed attention to the field of mixed metal oxides. Inorganic chemists have also contributed fundamentally to the field of materials chemistry by developing new methods for systematically controlling the size, shape, electronic properties, and interfaces of materials. These insights have provided the foundation for the development of new materials ranging from quantum dots, to molecular magnets, to new ferroelectric and dielectric materials. 3. Past Highlights in Catalysis As is the case for materials chemistry, contributions to the field of catalysis are judged not only by their utility in industrial and academic settings, but also by the insights that they


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provide into fundamental chemical reactions. Although many catalysts used industrially are heterogeneous, some of the greatest breakthroughs in this field have been in the development of homogeneous catalysts, for which rigorous characterization and mechanistic studies are available. Important examples include Wilkinson’s rhodium catalyst for hydroformylation and hydrogenation, the Ziegler-Natta family of catalysts for olefin polymerization, and the Sharpless catalyst that enantioselectively oxidizes olefins. 4. Past Highlights in Bioinorganic Chemistry Bioinorganic chemistry has emerged as one of the focal areas of Inorganic Chemistry. Its strong successes, stemming from basic research into the roles of metals in biological systems and enhanced by a highly collaborative environment, have had a wide impact on the development other fields. Important successes include: progress in understanding metal-ion catalysis in enzymes; the development of metal coordination compounds for imaging, diagnostics and therapeutics; the synthesis of biomimetic inorganic compounds that reproduce the structure of protein-based metal centers, and increasingly their function. Examples include detailed insights into the structure and function of metalloenzymes that perform multielectron transfer reactions on small molecules (cytochrome oxidase, nitrogenase, sulfite reductase and activate C-H bonds (methane monooxygenase); anticancer therapeutics based on Pt (i.e., cisplatin) and contrast agents for imaging and diagnostics based on Gd and Tc. The development of these medical applications has been guided by fundamental studies of the coordination chemistry of these elements. New highlights include progress in de novo design of metalloproteins (creating metalloproteins or peptides with new reactivities), in understanding how Nature synthesizes its metal-based biological catalysts, and expansion into areas such as the metallo-biochemistry of nucleic acids, and biogeochemistry 5. Past Highlights in New Length Scales The ability to synthesize materials with sub-100 nm dimensions has revealed important new insight into the relationship between the size, shape, and composition of nanostructures with their physical and chemical properties. At the interface of IC and materials science, great strides have been made in the past decade towards understanding the consequences of creating and working with materials on this difficult to access length scale. Recent developments include the rational synthesis of quantum dots allowing researchers to study size versus property effects and demonstrate the theory of quantum confinement. On a more fundamental level, workers in this area have made great strides towards understanding the factors that control the nucleation and growth of nanostructured materials such as nanorods, nanoparticles, and nanoprisms. In order to interrogate these novel architectures, advances in synthesis have been closely paired with the development of new lithographic techniques not only for characterization but also as tools for the directed assembly of materials and development of new chemical and biochemical detection strategies. Many of these strategies utilize the unusual properties of nanostructures to create detection systems with major advantages over conventional molecule-based approaches. These advantages include higher sensitivity, selectivity, and the ability to use very simple but elegant read-out mechanisms.


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Finally, the use of well-established coordination chemistry to assemble nanostructures in a bottom-up manner has seen major advances. The use of covalent coordination chemistry, through one of several well-developed approaches, has lead to the synthesis of many exciting molecular nanostructures with unique and unexpected physical properties. A key challenge for the next decade is to use these new synthetic capabilities to rationally build architectures that provide a better understanding of molecular recognition and to effect processes that rely on recognition (e.g. catalysis, chemical sensing, and molecular mixture separations). 6. Past Highlights in Environmental Inorganic Chemistry Environmental inorganic chemistry, by virtue of its many facets, is extremely broad in scope. Thus in these highlights and those in the subsequent section on frontier contributions are divided into three different areas, pollution prevention and resource conservation, inorganic chemistry in Nature, and the inorganic chemistry of contaminants.

• Pollution prevention and resource conservation o Chemical transformations using ‘green’ catalysts. o Utilization of non-traditional benign solvents such as supercritical fluids. o Manipulation of ozone chemistry in water purification and ozone removing

catalysts. • Inorganic chemistry in Nature

o Utilization of natural products and enzymes in bioremediation of contaminated land.

o Design and synthesis of biomimetic analogs of metalloenzymes and metalloproteins such as metal ion chelators.

• Inorganic Chemistry of Contaminants o Utilization of inorganic redox chemistry in remediation. o Utilization of supramolecular chemistry to extract targeted ions in

remediation. B. The Frontiers of Inorganic Chemistry Each thematic group was asked to articulate the current frontiers in their Area and to speculate on newly emerging frontier topics that also are likely to be important in that Area in the coming decade. The frontier topics identified in the workshop for each Area are summarized below. A table of frontier topics is provided in Appendix IV. The full record of the discussions in each Area is presented in Chapters 2-7. These frontier topics included in this report cannot be considered to be exhaustive, but the lists and discussions quite clearly illustrate the many challenges and opportunities for exciting, innovative, and societally important research in Inorganic Chemistry. 1. Frontiers in Core Topics While recognizing that it is inherently difficult to predict what advances will fundamentally alter how we as a community think about inorganic chemistry, we can still outline the characteristics of such a discovery and highlight important questions that need to be


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addressed. The conceptual or experimental advances that are of the highest priority are the ones that both cause a paradigm shift that we would expect all inorganic chemistry students to know about and also serve as starting points for other discoveries. Advances are expected to occur both in the way that scientific objectives are identified and in the approaches used to achieve specific goals. The fundamental way that new objectives or “targets” are selected will undoubtedly change as we enter the “information age”. In the past, targets have been defined primarily by individuals based upon their own scientific experience and intuition. Although this approach will never be superceded, investigators will supplement their own intuition with algorithms that result from advances from fields such as artificial intelligence, informatics, virtual reality, and computation and will use these techniques to refine their goals and identify specific targets. Many of the important new goals that are defined by both traditional and non-traditional methods will require new design principles or approaches if they are to be realized. For instance, given the tremendous wealth of inorganic compounds and reactions, new computer algorithms will be required to develop a comprehensive understanding of inorganic reaction chemistry that will allow scientists to perform inorganic retrosynthetic analysis on par with what is currently possible in organic chemistry. Although important new discoveries are often difficult to anticipate, there are several areas that provide particularly fertile ground for exploration of new paradigms application of new design principles. These include:

• The development of theoretical models for atom transfer and multi-electron transfer reactions;

• The discovery of fundamentally new reactions for making and breaking bonds; • The development of new methods for driving thermodynamically unfavorable

reactions; • The discovery of reactions and technologies that allow kinetically inert molecules

to be manipulated; • The investigation of single molecule and single bond reactions; • The development of new types of bonds, new functional groups, and new

paradigms for structure, bonding and reactivity; • The exploration of natural inorganic products; • The development of new molecular feedstocks for atom and group transfer

reactions; • The development of cascade (“one-pot”) reactions; • The development of new high energy (but kinetically stable) reagents for

inorganic synthesis; and • The discovery new synthetic methods.

2. Frontiers in Materials Inorganic Chemistry Although a whole host of new materials have been prepared in recent years, many challenges still await this field. Overarching goals include:


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• To develop a systematic understanding of synthetic phase diagrams for complex materials.

• To develop new molecular precursors that self-assemble into materials with interesting properties.

• To rationally control properties of materials to develop new superconductors, magnetic materials, photonic materials, catalysts, separation agents, and sensors.

• To prepare and accurately describe new amorphous and disordered materials with interesting magnetic, optical, electrical, or physical properties.

• To develop new methods for mesoscale or supermolecular assembly (e.g., for preparation of thin films).

• To develop ab initio and density functional theory methods that provide an accurate description of solid state compounds and the ability to predict the properties of new compounds.

3. Frontiers in Catalysis The primary challenges that await the field of catalysis fall into three main categories: new transformations, new mechanistic principles, and new approaches to catalyst discovery. Goals for new catalysts include the development of:

• Oxidation catalysts that are selective, inexpensive, environmentally benign, and use “green oxidants”, such as O2;

• Compounds that promote the conversion of nitrogen to ammonia and other amines at low temperatures and pressures;

• Catalysts that selectively convert hydrocarbons to primary amines, alcohols, and α-olefins or that regioselectively and chemoselectively convert arenes to phenols and anilines;

• Polymerization catalysts that tolerate a variety of functionalities on the monomers;

• Stereoselective, regioselective, and enantioselective catalysts for production of fine chemicals;

• Heterogeneous catalysts that exhibit high chemical- and stereoselectivity. To develop these new systems, a better fundamental understanding of reaction mechanisms is needed. Particularly fruitful areas for mechanistic studies include:

• Structure, dynamics and reactivity of highly unsaturated metal complexes, • New ligands that stabilizing transition metal reactive intermediates, • Discovery of new elementary reactions, • Understanding of how to control stereoselectivity, • Delineating the mechanisms of bioinorganic enzyme intermediates, • Identification of intermediates in heterogeneous catalysis, • Understanding of the dynamics of heterogeneous catalytic intermediates, and • Understanding of catalytic events that occur under extreme temperatures and

pressures.


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In addition, the development of techniques for the discovery and development of new catalysts will be essential to this field. The advent of “green solvents” such as supercritical CO2 provides an important illustration of how important it is to develop a fundamental understanding of how a wide variety of factors (including the solvent system) affect catalyst performance. Fundamental studies at the interface of heterogeneous and homogeneous catalysis are also needed, including the development of new support strategies for homogeneous catalysts. Advances in the emerging field of nanotechnology (see New Length Scales) and are expected to dovetail with these efforts. Likewise, developments in theoretical chemistry, particularly for studying larger systems, are expected to provide a driving force for the rational design of new catalyts. Combinatorial and high-throughput methods are needed that will allow reactivity and selectivity to be rapidly screened. New approaches to ligand design that allow for modularity or provide unique architectures are also needed. The field of catalysis also bridges into biological chemistry (see Bioinorganic Chemistry) and new developments in Biotechnology offer insights into entirely new approaches to catalysts development and design. For instance, the field of “directed evolution” (in which protein catalysts are subjected to selective pressure to produce new reactivities) has recently been adapted to the development of artificial evolution in purely chemical systems. Another exciting new approach to catalysis is the development of programmable tandem reactions (or reaction networks), in which the reactions of multiple catalysts are coordinated to synthesize complex molecules from simple molecular building blocks. 4. Frontiers in Bioinorganic Chemistry Current and future frontier research in Bioinorganic Chemistry builds on its current successes, as well as on discoveries of the past decade that have opened up entirely new areas. As advances in genetics, structural biology, spectroscopy and synthesis have bolstered recent efforts, new tools in bioinformatics, genomics, and nanotechnology will continue to open additional frontiers of the field. The Frontiers discussed in Chapter V include, but are not restricted to the following:

• Metalloenzymes and ribozymes, natural and engineered • Inorganic chemistry of the cell (‘metallome’) • Inorganic Chemistry of Health and Disease, including metallo-drugs and imaging

agents, metalloneurochemistry and biological NO chemistry • Bio-metallo Sensors • Biomaterials, including biomineralization and adhesion • Functional Biomimetic chemistry and green chemistries • Environmental bioinorganic chemistry

5. Frontiers in New Length Scales While many exciting advances in the area of nanoscale IC have been realized in recent years, there are both fundamental and more sophisticated scientific questions to be answered. The following areas are only a few examples of research topics at the forefront of this quickly


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growing field:

• The control of both size and shape in the synthesis of nanomaterials. • The understanding of how composition, size, and shape affect function. • The definition of the inherent limits of molecular purity of nanoarchitectures. • The development of new techniques to interrogate, manipulate, and characterize both

the bulk and surface properties of nanomaterials. • The controlled synthesis and understanding of composition versus function

relationships in binary and ternary solids. • The expanded control of supramolecular coordination chemistry to include

architectures with dimensions in the 2-10 nm length scale. • The rational, controlled, and low-temperature synthesis of nanotubes (carbon

included) of various lengths and composition. • The continued development of theoretical methods to aid in the understanding and

implementation of most, if not all, of the above research topics. 6. Frontiers in Environmental Inorganic Chemistry

• Pollution prevention and resource conservation (Green Chemistry): o Revolutionizing industrial processes by design to feature atom economy,

environmentally benign reagents, and alternative ‘green’ reaction media. o Providing and improving new types of energy sources by developing solid

state materials that store hydrogen as densely as hydrocarbons, devising a means of producing hydrogen without CO2 as a byproduct, finding a way to decompose water to produce hydrogen in an energy efficient process, and utilizing methane as a fuel.

o Understanding speciation to address environmental needs by its atmospheric and terrestrial geochemistry, its bioinorganic and biogeochemistry, and the reactions and relationships between phases of its environmental cycle (mineralogy, aqueous chemistry, etc.).

• The environmental inorganic chemistry of contaminants o Understanding the fundamental inorganic chemistry and environmental

behavior of contaminants and developing better in situ stabilization and monitoring methods.

o Developing and implementing new remediation techniques by inorganic and multi-disciplinary research on molecular recognition, uptake and metabolic processes for inorganics in plants and microorganisms, genetic engineering, and plant/bacteria symbiosis.

o Developing more highly selective receptors and sensors capable of multi-analyte detection and selective extractants and sequestering agents.

• The role of theory in environmental inorganic chemistry o Accurately modeling microscopic and macroscopic phenomena under “real”

conditions, such as in solution or within a solid support. o Merging accurate quantum chemical approaches with methods for the

accurate prediction of transport properties to enable modeling of geochemical and biogeochemical phenomena.


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o Developing new methods of informatics for mining existing data on environmentally relevant inorganic molecules.

C. Connections Between Thematic Areas and Opportunities for Cross-Disciplinary Work The attendees of the Workshop accepted that IC can be usefully grouped into the six Thematic Areas employed above, while taking great care in optimize the definitions and set of topics encompassed by each Theme. However, this division hides strong commonalities of methodology and approach that link them. Several methodological approaches and intellectual foundations are common to all Areas of Inorganic Chemistry. For instance, all six Areas which encompass Inorganic Chemistry incorporate a synthesis component: Inorganic Chemistry, like Organic Chemistry, is built on the creation of new kinds of matter - new molecules and new collections of atoms and molecules. But IC is involved not only in making new matter, but also in understanding the processes which create it and the matter being created. The former leads to a common interest in mechanism; the latter to a common incorporation of spectroscopy as a means of characterizing both stable compounds and reactive intermediates, and of theoretical approaches towards understanding and prediction. Further, there is considerable commonality in research topics/goals. Thus, while there is an Area denoted ‘Catalysis’, every Area is involved with some aspect of this topic. Likewise, although there is a Bioinorganic Area, every Area of Inorganic Chemistry has at least some component aimed at biologically directed or inspired research. Other issues that have wide communal interest include, for example, interest in sensing/recognition and in electron-transfer processes. Given this commonality of methods and goals, it is not surprising that interactions between Thematic Areas provide fertile ground for new cross-disciplinary initiatives. Examples include:

• Biocatalysis related to design of new catalysts, industrial processes • Environmental Bioinorganic chemistry:

o Bioremediation o Microbial-mineral interactions o Biogeochemistry o Toxic metals

• Inorganic chemistry in neuroscience • Biogeochemistry

IV. BALANCE This section briefly summarizes the views of the Workshop on the two issues posed to it that are of importance in the actual prosecution of research in Inorganic Chemistry.


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A. Single- vs. Multi-Investigator Funding Models The Workshop was asked to consider the proper balance between between single-investigator and multi-investigator funding mechanisms. Much of the research in Inorganic Chemistry is highly collaborative; in some areas, such as Environmental or Bioinorganic Chemistry, most of the research being conducted today is collaborative. However, in most instances it is felt that flexible collaborative arrangements among individually funded investigators provides the optimum research/funding paradigm. Many of the workshop participants firmly believed that the autonomy afforded an investigator to initiate and terminate collaborations as research directions and rates of individual progress vary maximizes the research productivity of all investigators. Nonetheless, this paradigm does not fit all situations. Certainly, if major shared equipment or facilities are needed, the multi-investigator mode is demanded. Likewise, long-term shared interests and goals may demand synchronous funding among the set of collaborators. B. Fundamental vs. Directed/Applied Research: A False Dichotomy A second issue of ‘Balance’ involves a sometimes-perceived dichotomy between ‘fundamental’ and ‘directed/applied’. The Workshop was unanimous in viewing such a dichotomy as false. Research in Inorganic Chemistry of even the (apparently) most esoteric kind commonly has a temporal evolution in which fundamental breakthroughs are recognized as having broader impact and application. Conversely, research (apparently) focused on a narrow goal may well yield fundamental breakthroughs. V. EVALUATION OF WORKSHOP BY PARTICIPANTS The participants were asked to complete a questionnaire evaluate the effectiveness of the workshop before departing; nineteen responses were received by the organizers. High marks (unanimously “excellent” to “OK”) were given for communication from the organizers about travel arrangements, the meeting facilities at Copper Mountain, the onsite staff at Copper Mountain, and the meals. The evaluations of Northwestern Travel and the choice of Copper Mountain as a meeting site were slightly mixed, with one participant ranking each of these as “poor”. Most participants felt that the length of the workshopg was “just right” and some felt that is was “somewhat short”; none felt that the workshop was too long. Likewise, most participants felt that the amount of free time, time allocated for breakout sessions, and time allocated for panel discussion was either “just right: or “almost enough”. Graphical representations of these results and a complete list of all comments and suggestions provided by the participants are provided in Appendix V. VI. SUMMARY OF WORKSHOP EXPENSES The award from the National Science Foundation ($59,400) was used to cover travel expenses, lodging, and meals for the workshop participants. The travel expenses and lodging for representatives from NSF and DOE were paid directly by the agencies that they represent and not from the workshop budget. A small portion of the budget was used to cover additional meeting expenses, such as supplies (e.g., charts and pens for breakout groups),


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photocopying expenses, and rental of audiovisual equipment. The total expenditure for the workshop was $47,698.22. The $11,701.78 of the original award that was not spent was returned to the National Science Foundation. A copy of the Final Financial Report from Northwestern University is included in Appendix VI. Acknowledgements. This workshop on the Frontiers of Inorganic Chemistry was the brainchild of Marge Cavanaugh and would not have been possible without the backing and assistance of Nick Serpone at the National Science Foundation. N.S. and the Group Leaders (Christopher Cummins, Jillian Buriak, Susan Kauzlarich, John Hartwig, Victoria De Rose, Chad Mirkin, and Mary Neu) helped to assemble the list of participants and provided helpful suggestions in the planning phase. The success of the workshop is due in large part to the enthusiastic input of all of the participants (see Appendix II for complete list). The organizers are also extremely grateful to John Magyar, who took care of the on-site administration of the workshop. The report was prepared using the individual topic reports that were compiled by the group leaders and using notes taken by John Magyar and Katharine Covert. Mike Clarke provided critical editorial comments on drafts of the report.


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Chapter 2 – Detailed Report on Core Topics Group Leader: Christopher Cummins Contributors: Daniel Nocera Jonas Peters Malcolm Chisholm Gregory Robinson John Gilje I. PAST HIGHLIGHTS IN CORE TOPICS Past milestones in inorganic chemistry have given rise to paradigm shifts and provided concepts and themes that constitute the fundamentals of inorganic chemistry as they exist currently. Some illustrative examples of relatively recent milestones are listed in the following:

• Weakly coordinating anions • Enantiomorphic site control in single-site Ziegler-Natta catalysis • Fixed-distance electron transfer • Metal-metal multiple bonding in molecular systems • Frontier molecular orbital theory of organometallic reactions

Consideration of such important past achievements provides inspiration for future fundamental advances. The examples are illustrative, qualitatively, of those features that characterize a fundamental advance. II. FRONTIERS IN CORE TOPICS In considering what new fundamentals may arise in the future of inorganic chemistry it seems profitable to consider possible avenues of investigation in terms of the following questions: “What are the emerging principles that inorganic chemistry students of the future will need to know?” “What experiments or paradigms will serve as starting points for seminal advances?” Having articulated the preceding questions and having recognized the need for pedagogical utility as one criterion for the new fundamentals, it might be said that all areas of inorganic chemistry activity have in common the need for a target, and the need to connect that target to the available building blocks. Some attention should be devoted to the process of selecting a target, whether it be it a novel technetium compound needed for medical imaging or a solid-state material desired for testing of theoretical models of magnetism.


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Thus a chemical endeavor can be broken down schematically into two kinds of activities:

1. Target selection 2. Target acquisition

With reference to the accompanying diagram entitled “Conceptual Advances for Design” one sees the distinction between target selection and target acquisition illustrated schematically. Target selection traditionally has been an experiential process, i.e. derived from a particular investigator’s training in a subspecialty of inorganic chemistry. Inorganic chemists with an interest in biological processes are likely to select targets relevant to same, traditionally metalloenzyme targets or, more recently, targets having ties to neuroscience or biological imaging. Similarly, inorganic materials chemists or those whose interests can be identified with well-funded current initiatives such as nanotechnology tend to prefer target selection in accord with those interests. Often, the process of target selection can be construed as an attempt to improve on previous work, to understand systems still shrouded in mystery, or to fill gaps in the existing framework of achievements. Societal needs also drive target selection. This is particularly evident in projects aimed at environmental sustainability and green chemistry. Targets oriented at improving human health fall also into this niche, and have the attractive property that they can be said to be pre-justified with respect to the obviousness of their importance. As will be touched upon below, however, advances in areas directly tied to obvious societal need are fueled by and usually readily traced to the fruit of purely curiosity-driven research. In the future one can envision new methods of target selection to augment the traditional approaches. These might take advantage of advances in computation and artificial intelligence, virtual reality, informatics applied to the chemical literature and reaction system databanks. In other words, the information age may be expected surely to lead to less-than-intuitive methods for specific target selection once a desired goal concerning properties and constraints have been prepared as input. Development and implementation of such new ways to conceive of an idea may well turn out to best be achieved within the context of multi-investigator collaborations organized to draw upon talent from the chemical sciences together with talent from mathematics and computer science. Now having selected a chemical target for synthesis or study, we turn our attention to the relationship between that target and the building blocks that may lead to it. This relationship can be viewed from both vantage points, that of the building blocks or starting materials, and from that of the target itself. Either way, two components can be taken to comprise that relationship, these being Design Principles and New Chemical Discovery, the latter being perhaps another way of saying Fertile Ground for Exploration. It will be of interest to consider possible advances in both areas that might appear over the next decade or two. Some possibilities appear in the following bulleted sections.


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Design Principles • Inorginformatics – this term may be coined to represent the implementation of

automated database- and computer-aided methods for retrosynthesis and for the choice of particular strategies and reaction conditions.

• New Assembly Methods – here we take inspiration from the traditional methods of spontaneous self-assembly and templated building up of systems to suggest that novel approaches will appear

• Inorganic Retrosynthesis – synthetic methods and strategies for inorganic chemistry are as diverse as the periodic table itself. The challenge to organize these and to identify underlying strategic and tactical themes in inorganic synthesis should be undertaken and be not only of pedagogical utility but also will feed ultimately into computer-aided approaches to designed synthesis.

• Quantitative Interplay between Theory and Experiment – in the past qualitative theories (such as FMO methods) have spurred tremendous advances in understanding and in prediction. With the advent of modern DFT methods and other advanced computational and modeling approaches there is great opportunity for a shift to a quantitative interplay. Physical and spectroscopic properties may be calculated with high accuracy and will go hand-in-hand with experimental work on a daily basis.

• Exploitation of Inorganic Secondary and Tertiary Structure – just as biopolymer-comprised systems are organized at several levels, so will inorganic systems be for molecular, supramolecular, and solid-state systems.

New Chemical Discovery

• Beyond One-Electron Reactivity – adequate theoretical models for the description of atom transfer reactions and multi-electron transfer processes have not yet been developed and provide a challenge to modern theorists. Developments in theory will stimulate growth in this fertile area on the experimental side.

• Bond-Breaking and Bond-Making Processes – new ways to elicit fundamental chemical transformations in inorganic systems from molecular ones to clusters and in the solid state are ripe for development. Our present toolkit of available processes is stunningly small given the complexity and diversity possible for inorganic systems.

• Thermodynamically Unfavorable Reactions – reactions that use light to drive an otherwise uphill process are energy-storing reactions relevant to photosynthetic systems. Our state-of-the art in this regard is woefully inadequate and this area warrents much vigorous attention.

• Manipulation of Kinetically Inert Molecules – feedstocks that are readily available but kinetically inert will be manipulated exquisitely to great advantage by inorganic systems of the future. These include nitrous oxide for oxidation and methane for conversion to liquid fuels.

• Single-Molecule –Bond Reactions – advances in laser technology and experimentation will drive the study of inorganic reaction mechanisms at the single-molecule level. This will likely require multi-investigator collaborative initiatives.

• New Bonds Between Atoms – inorganic systems of the future will feature


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previously unanticipated patterns of connectivity between elements from all corners of the periodic table. New functional groups will be defined and their chemistry explored. Paradigms for structure, bonding, and reactivity will emerge slowly as new motifs are implemented for inorganic systems on all size scales.

• Natural Inorganic Products – sources of inspiration will be derived from both terrestrial and extra-terrestrial sources as the universe is mined from sea-bottom to outer space for examples of unanticipated structural types with exotic associated function.

• Non-traditional Molecular Feedstocks for Atom and Group Transfer – inorganic chemists will seek to derive desirable functionality from previously unutilized or underutilized sources.

• Cascade Reactions – existing inorganic syntheses that currently are lengthy or inefficient will be improved so as to combine several sequential steps into one-pot processes, minimizing waste and saving time.

• High-Energy Reagents for Inorganic Synthesis – explosive components will be harnessed to deliver efficient access to high-energy but kinetically stable inorganic functional groups.

• Exploratory Synthesis and New Synthetic Methods – areas of inorganic synthesis that have traditionally been neglected in the U.S. (such as main-group chemistry with the exception of organic chemistry) will be systematically developed, fueling advances in the more applied branches of the discipline.

Conceptual Advances for DesignBuilding Blocks(e.g. molecules, atoms)

Target

- Design Principles- New Chemical Discovery

- Virtual Reality- Computation- Informatics

Experiential- biomaterials- nanotech- etc.... Societal Needs

Targ

etSe

lect

ion

Targ

etA

cqui

sitio

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17

Chapter 3 – Detailed Report on Materials Inorganic Chemistry Group Leader: Susan Kauzlarich Participants: Gui Bazan Jillian Buriak (in absentia) Malcolm Chisholm Kim Dunbar Richard Eisenberg Brian Hoffman Jeffrey Long Chad Mirkin

I. PAST HIGHLIGHTS IN MATERIALS INORGANIC CHEMISTRY The development of new materials is an important cornerstone of new technologies and inorganic materials that constitutes a critical area of Inorganic Chemistry. There is a tremendous variety of inorganic materials and many have led to important new applications and discoveries. An excellent example is the synthesis of new zeolites such as ZSM5 which is used to catalyze a number of processes including hydrocarbon cracking (Figure 3.1)11

Another very dramatic illustration is the discovery of the high temperature superconducting copper oxides (Figure 3.2).2 This event catalyzed a renaissance of research in the area of synthesis of mixed metal oxide solids. Today, emerging areas, some central to inorganic chemistry, and others with a cross-disciplinary flavor, promise advances in fundamental understanding of inorganic material structure, and novel technologies designed to enhance quality of life. In addition to more traditional disciplines of solid-state chemistry, there are many new areas of solid-state and materials chemistry in which Inorganic Chemists are having a huge impact. Some of the most exciting developments in the field are based on a desire to control the size, shape, electronic properties, and interfaces of materials; examples of the fruits of these endeavors are quantum dots and wires, zeolites, ferroelectric and dielectric materials, novel magnetic materials such as molecule-based magnets, and single-molecule magnets. There have also been important developments in the control of composition

Figure 3.2 The structure of YBa2Cu3O7

Figure 3.1 The structure of ZSM5


18

to prepare new and better superconductors, dielectric and ferroelectric materials, thermoelectric materials, and colossal magnetoresistive materials. To organize this topic, we have divided materials into two basic types:

1. Materials based on molecular building blocks (materials derived from molecular precursors and materials based on collections of molecules);

2. Materials based on extended lattices. Materials included in (1) are biomaterials, coordination and main group polymers, films ("self" assembled systems), hybrid inorganic/organic materials, mesogens (liquid crystals), and amorphous/glassy materials. Materials included in (2) are biomaterials such as bone and materials for structure and biological supports, ceramics, intermetallics, thermoelectrics, dielectrics, ferroelectrics, zeolites and semiconductors. Nanomaterials and materials for catalysts are being covered in another section and will not discussed here. This overview is not meant to be all encompassing, but it provides a glimpse of the vast array of materials that are of interest to inorganic chemists and which have significant potential for future technologies. II. FRONTIERS IN MATERIALS INORGANIC CHEMISTRY The interest in inorganic materials is broad and includes materials prepared by more traditional high temperature routes, and those that are accessible only through low temperature solution phase approaches. Much of the future can be couched in terms of the basic interests of chemists: synthesis, structure, and properties, with an aim towards new materials with properties that may be useful in future technologies. It is our opinion that these are some of the areas that have potential for high payoff in the form of important technological discoveries. Although it is not possible to predict exactly which breakthroughs will be made in the next decade, it is possible to foresee that many exciting new opportunities and research areas will arise. A. Synthesis One of the fundamental issues regarding research in materials is synthesis, and it remains a frontier area. Synthesis, along with its optimization, is the most important starting place for the discovery of new materials. It is well known that the final performance characteristics of materials depend strongly upon the synthetic approach and processing. The use of phase diagrams, along with hypotheses of important components for particular properties, provide useful starting places for many synthetic endeavors. However, with increasing complexity of materials, there is a lack of appropriate or complete phase diagrams. Chemists are often systematically investigating phase space with an eye toward new structures with possible unprecedented properties. Molecular approaches to new materials offers several advantages including high-purity precursors and control of structure. The use of molecular precursors in solution to build self-assembled materials adds a new dimension to the world of novel materials with unique capabilities. Moreover, molecular precursors can provide a better route to existing materials and this approach is particularly well-suited to areas of materials chemistry aimed at building more complex materials with specific applications or functions


19

in mind. It has been pointed out by other NSF Workshops that a vast area of phase space is still largely unexplored. A pointed example is the fact that only 0.01% of all possible quaternary intermetallic compounds have so far been investigated.3 This presents an exciting frontier with the emphasis of synthesis of new materials by design. B. Properties The control and predictability of a material's property continue to be key for the advancement of new materials. Specific target areas for future research are superconductivity, materials for microelectronics (new barrier materials, ferroelectrics, dielectrics), photonic materials, magnetic materials, catalysts, and separation and sensor materials. The new, unprecedented discoveries of the rare earth borocarbide and MgB2 superconductors, and the new high-temperature superconductivity in lattice-expanded C60 suggest that this area still holds a great deal of promise. Property control is an area in which both chemists and physicists are working to design and characterize novel materials. In addition, there exists an important component of materials synthesis and processing in preparing superconducting ceramic materials in useful form. In the microelectronics area, the need for new carrier diffusion barriers presents a challenge for inorganic chemists: how to synthesize refractory materials via low temperature routes to produce surface coatings. There is a need for better ways to make existing materials and much of this effort ties in with efforts in nanomaterials. The cellular industry requires new dielectrics, including ferroelectrics. These insulating ceramics are widely used in electronic applications as actuator, transducer, multiplayer capacitor, and resonators or filters for wireless communication. Advanced materials with improved dielectric response as a function of temperature, chemical environment, size limitations, device frequency, and/or operating power are in continuous demand by designers of next-generation applications. Nearly all currently used ceramics have been developed empirically, owing to the absence of a general predictive theory for dielectric phenomena. Rational design of new materials, and improved processing of existing materials, require fundamental research (Figure 3.3)4 to determine transferable chemical and structural aspects that can be used for the prediction of high-frequency dielectric behavior. There is a strong drive to develop the interfacial chemistry of semiconductor5 and superconductor surfaces,6 through which a wide range of different groups may be covalently attached through, for instance, kinetically and thermodynamically stable E-C bonds (where E = Si, Ge, Ga/As, etc). These linkages avoid the electronically defective and essentially invariable oxide coating which has been the mainstay of the semiconductor industry up until now. Because of the versatility and promise of this chemistry, the surface can be modified at will to, for example, be linked to biological molecules, receptor molecules for sensor application, various groups which will allow separations on semiconductor-based lab-on-a-chip applications, and many other technologies. Figure 3.4 shows an example of organically modified porous silicon.


20

The development of novel photonic materials provides new ways of storing information via optical switches. These types of materials impact computers and sensors. There is a large overlap with more applied areas of research, along with interest in nanomaterials. Materials for separation and sensors overlap with nanomaterials. Open framework structures with designed-in functionality have great potential. Utilizing materials such as porous silicon as a substrate can provide great advantages in controlling functionality. Complex materials based on organic-inorganic hybrids provide a new component that allows even more flexibility in structure and properties.

Thermoelectric materials have excellent potential for major technological impact in the future. A thermoelectric cooler maintains temperature control dynamically. It can lower the temperature of an object below ambient as well as stabilize the temperature when it is subject to widely varying conditions. The materials are complex non-oxidic solids such as tellurides, selenides, antimonides, and intermetallics. While these materials are Figure 3.5. The structure of the CsBi4Te6

Figure 3.3 Illustrations of the perovskite-related structures of three polymorphs of Ca4Nb2O9 with different B-site cation orderings (blue: Nb, tan: Ca, stippled: mixed Ca/Nb); dielectric properties depended systematically on bonding details.4

1:1 (P21/a)

LT1/4 (P1)

2:1 (P21/c)

Figure 3.4. 1 cm diameter porous silicon samples photoluminescing under UV irradiation. a) A triply photopatterned porous silicon structure. The area that spells out “1-decene” is a decyl-functionalized surface; the “styrene” area is a phenethyl surface; the “1,5-COD” area is a cyclooctenyl surface. The reacted areas are slightly redshifted and darkened as compared to the PL of the unreacted regions of the sample. b) the same sample after exposure to boiling pH 12 KOH solution; only the derivatized areas are still photoluminescent due too their robust capping after this drastic chemical treatment.


21

already having a technological impact, there is a great deal of room for improvement in conversion efficiency. Figure 3.5 shows the structure of a new material discovered through exploratory synthesis.7 Magnetic materials comprise an area with a great deal of potential for new discoveries. Colossal magnetoresistance, transparent ferromagnets, half-metallic ferromagnets, and high temperature ferromagnetic molecular magnets are just a few examples of exciting recent discoveries. There is a large endeavor in the area of nanomagnets, both particles and molecules. The idea that a single molecule can have a large spin that could be controlled has led to novel metal oxo clusters and new directions in metal cluster chemistry. Advances in chemical synthesis now permit design of single molecules with large magnetic moments. As we move toward the coupling of these molecules both electrically and magnetically, their impact on materials science may be comparable to that of fullerenes and nanotubes. The future will witness the expertise of synthetic chemists in the design and synthesis of nanoscale magnetic molecules coupled with the knowledge of experimental and theoretical solid state physicists in the characterization, analysis, and prediction of magnetic and electronic behavior of magnetic nanostructures (Figure 3.6).8 The main goals are (1) to design and synthesize new nanoscale molecules with specific properties, (2) to understand the quantum properties of these large moment molecules, (3) to assemble new nanostructures from these molecular building blocks that will exhibit magnetic and electronic effects useful for new technologies, and (4) to understand the collective interaction of these molecules in complex nanostructures. C. New States of Matter Disordered inorganic glasses or amorphous collections of independent molecules find uses in multiple applications, more recently in devices where charge transport and optical properties are important. Aerogels and mesoporous materials (which are amorphous on an atomic

Figure 3.6 Structure of [BEDT-TTF]3[MnCr(ox)3], the first molecule-based metal ferromagnet, showing the alternating magnetic (ferromagnetic) and electrical (metallic) multilayers


22

length scale) can also be included here. There is significant interest in electronically active aerogels and mesoporous materials for sensor and electrochemical applications. A proper description of the amorphous state is lacking, as well as how molecular topology translates into bulk morphology. Fundamental studies in this area are needed. Dual-property materials or “smart” materials that result in supercaloric materials, colossal magnetoresistive materials, thermoelectric materials, and optoelectronic materials are included in this area. All of these types of materials have ample room for further development of both materials and our level of understanding. This folds into new length scales with quantum confinement and single molecule magnets. There are new opportunities in microporous magnets and conductors. In terms of the molecular materials, much of this research is interdisciplinary and involves the design, preparation, and study of physical properties of molecular assemblies and polymeric materials exhibiting relevant magnetic properties together with other useful chemical, physical, electrical, or optical properties. The quest in this area of research is not just to obtain molecule-based compounds than can behave as classical solid-state magnets, showing spontaneous magnetization below a certain temperature Tc, but also to produce materials that may exhibit completely new physical properties or those in which the magnetic properties are combined with other physical properties. Examples of such systems could be materials showing bistability, tunable magnetic ordering temperatures, discrete molecules showing magnetic hysteresis (nanomagnets), hybrid materials coupling magnetism with conductivity or even superconductivity, or with optical properties. Other interesting phenomena that are being contemplated are: magnetic tunneling, quantum gaps, long-lived photo-optical excited states solids with restricted magnetic dimensionalities such as spin ladders and frustrated networks. Much of the success in this area depends on the evolution of new synthetic strategies to construct molecules at the mesoscale level as well as those techniques that allow an accurate control, either in solution or in the solid state, of supramolecular assemblies. It is also important to prepare the new magnetic materials in such a way as to take full advantage of their properties in devices. This includes the formation of thin layers and organized films, encapsulation, intercalation, and others. The development and improvement of experimental techniques such as high-field/high-frequency EPR and NMR spectroscopies, polarized neutron scattering, muon spin rotation experiments, magnetic and heat capacity measurements at very low temperatures, that help to characterize the resulting materials and to study the most interesting magnetic phenomena are also relevant to this area of inorganic chemistry. D. Frontiers in Theory Another important subject is the development of suitable models and theories for solid-state compounds − ab initio and density functional theory methods − that permit inorganic chemists to understand the properties of materials and even to predict the intra- and intermolecular magnetic interactions occurring in molecular assemblies. Such computational investigations will provide insight into the structure and properties of novel materials and hypotheses for further enhancement of physical properties.


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References for Chapter 3 (1) Taken from the Atlas of Zeolite Structure Types (http://www.iza-sc.ethz.ch/IZA-

SC/Atlas/data/MFI.html). (2) Taken from the website: www.thi-berlin.mpg.de/th/personal/hermann/pictures.html. (3) Kauzlarich, S. M.; Dorhout, P. K.; Honig, J. M. J. Sol. State Chem.2000, 3. (4) Levin, I.; Chang, J. Y.; Geyer, R. G.; Maslar, J. E.; Vanderah, T. A. J. Sol. State

Chem. 2000, 156, 122. (5) Schwartz, M. P.; Ellison, M. D.; Coulter, S. K.; Hovis, J. S.; Hamers, R. J. J. Am.

Chem. Soc. 2000, 122, 8529. Buriak, J. M. J. Chem. Soc., Chemical Communications, 1999, 1051. Buriak, J. M. Chem. Rev. in press.

(6) Xu, F.; Zhu, J.; Mirkin, C. A. Langmuir, 2000, 16, 2169-2176. Lo, R. K.; Ritchie, J. E.; Zhou, J. P.; Zhao, J. N.; McDevitt, J. T.; Xu, F.; Mirkin, C. A. J. Am. Chem. Soc. 1996, 118, 11295.

(7) Chung, D.-Y.; Hogan, T.; Brazis, P.; Rocci-Lane, M.; Kannewurf, C.; Bastea, M.; Uher, C.; Kanatzidis, M. G. Science 2000, 287, 1024.

(8) Coronado, E.; Galán-Mscarós, J. R.; Gómez-Garcia, C. J.; Laukhin, V. Nature 2000, 407, 447.


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Chapter 4 – Detailed Report on Catalysis Group Leader: John Hartwig Participants: Karen Goldberg Gui Bazan Chuck Casey Malcolm Chisholm George Stanley Jim Espensen I. INTRODUCTION Catalysis is a common theme in inorganic chemistry, and has even been considered its own subdiscipline. The chemical industry relies on catalytic processes, and the output from catalysis increases annually. The manufacture of polyethylene alone increased from an annual production of 2339 tons in 1980 to more than double (5743 tons) in 1990. New processes for commodity chemicals were installed in the last decade and some of the classics were improved with new catalyst structures. Catalysis are typically divided into homogeneous, heterogeneous, and more recently biocatalysts. Homogeneous catalysis arguably came into its own with hydroformylation with cobalt carbonyl discovered by Otto Roelen1,2 and the development of Wilkinson’s rhodium catalyst for both hydroformylation and hydrogenation.3,4 These homogenous catalysts provide activity and selectivity that make them superior to heterogeneous catalysts for many applications. However, the use of heterogeneous catalysts clearly simplifies product separation and has used more frequently in large-scale industrial processes. In the largest scale chemistry of any type conducted in industry, heterogeneous catalysts clean, crack and reform hydrocarbons. In some cases, designer heterogeneous catalysts, including zeolites, have been developed because of their high surface area that enhances overall activity and controlled pore size that controls selectivity. II. PAST HIGHLIGHTS IN CATALYSIS Several stunning discoveries have been made in catalysis in recent years that will provide the fuel for the next decade’s commercial developments. Only a selection of these developments and discoveries can be summarized here. We provide a few to allow the reader to experience the diversity of transformations that have emerged. These areas are divided into five different types of chemical transformations.

• Olefin Polymerizations • Olefin Metathesis

Figure 4.1 The GNP generated by catalysis in the U. S. rivals the total GNP of several industrialized countries.

0

0.5

1

1.5

2

2.5

3

Country

Japan Brazil CanadaFrance Germany SwitzerlandUS Catalysis


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• Carbonylation Reactions • Oxidation Catalysis • Asymmetric Catalysis

A. Olefin Polymerization A major breakthrough in olefin polymerization was achieved by the landmark discovery of Ziegler and Natta in 1953.5,6 More recently, single-site, constrained geometry catalysts have been invented, some based on synthetic inorganic chemistry in the laboratories of Brintzinger7 and Bercaw.8 These catalysts provide fast rates and exquisite control over polymer architecture and stereochemistry. Stereoregular polypropylene can now be generated from Brintzinger’s C2-symmetric bis-indenyl zirconium compounds,7 while copolymers of ethylene and α-olefins are prepared with the “INSITE” technology at Dow.9 A number of modifications earlier catalysts have provided novel polymerization catalysts. For example, Brookhart10-12 modified the bis-imine complexes studied by Vrieze13,14 and Grubbs15 modified SHOP-type ethylene oligomerization catalysts to generate late metal initiators of ethylene polymerization that begin to tolerate functional groups. Even middle transition metals complexes – when modified with the proper ligands – are highly active ethylene polymerization catalysts, as shown by Brookhart, Gibson and Bennett.16-19

TiNR

Si

ClCl ZrCl Cl

NPd

N

Me THF

NNi

O

Me NCR

Bercaw's "ContrainedGeometry Complexes"

Brintzinger's "Ansa-Metallocenes"

Brookhart's bis-imine complexes Grubb's modified SHOP complexes

B. Olefin metathesis Olefin metathesis began with poorly defined heterogeneous catalysts that displayed moderate activity at low temperatures. However, studies over a number of years by Schrock20,21 and Grubbs22,23 uncovered the mechanism of this process using well-defined complexes, and these studies have now led to catalysts with remarkable activity at low temperatures and high functional group tolerance. Once restricted to the synthesis of bulk chemical feedstocks, this process has now infiltrated fine chemical synthesis because of the ambient conditions and functional group versatility. Ring closing metathesis22 provides an alternative to Wittig chemistry, and ring-opening metathesis24 provides block copolymers and polymers with hydrocarbon backbones and pendant functionality.


26

N

MoCHR

(F3C)2HCO(F3C)2HCO CHRRu

ClCl

C

PR3

NN ArAr

Schrock Catalyst Grubbs Catalyst C. Carbonylation Hydroformylation chemistry was invented in the 1930’s, but major advances in this reaction and other carbonylations were even made in the 1990’s. Hydroformylation has been developed into a process with several catalysts that now generate linear aldehyde with high selectivity. New developments have more recently allowed for preparation of linear aldehydes from internal olefins using the rhodium catalysts with high activity.25,26 In addition, Shell chemicals developed a new process that generates propanediol from practically earth fire and water – actually carbon monoxide that can be generated from coal and ethylene oxide that they make from ethylene and oxygen.27,28 Propanediol is the monomer used to prepare polyesters such as those molded into clear plastic bottles. Even the classic acetic acid synthesis has been changed. New iridium catalysts provide higher activity with certain promoters that were obtained with rhodium.29,30 D. Oxidation Metal complexes are required for catalytic oxidation. Half of this year’s chemistry Nobel Prize in 2001 was awarded to Barry Sharpless for his work in enantioselective oxidation of olefins.31,32 Recent discoveries in selective activation of C-H bonds has generated promise for selective hydrocarbon oxidations. In the last decade, the most active and selective catalysts for methane oxidation, in this case to produce the methanol derivative methyl sulfate, was discovered by Roy Periana at Catalytica.33,34 E. Asymmetric Catalysis In the past decade, several asymmetric catalytic reactions have become a mainstay of fine chemicals synthesis. Asymmetric formation and opening of epoxides can now be conducted with broad scope.35 Asymmetric dihydroxylation and aminohydroxylation now efficiently provides optically active diols and diamines.36-38 Asymmetric hydrogenation and transfer hydrogenation of ketones and imines now generates optically active alcohols and amines, with high turnover numbers, with high turnover frequencies, and with broad substrate scope.39,40 Even asymmetric carbon-carbon bond-formations – such as dialkylzinc additions to aldehydes, asymmetric Michael additions, and Lewis-acid mediated Diels-Alder reactions – are beginning to see use in synthesis.


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III. CHALLENGES Discussions of the chemical challenges that catalysis can tackle were divided into three broad categories: new transformations, new mechanistic principles and new approaches to catalyst discovery. These three classifications are naturally interdependent. New approaches to catalyst discovery will lead to important new transformations, and mechanistic information will be used to discover new transformations. Of course, the discovery of new reactions also leads to a flurry of mechanistic studies with the goal of uncovering new principles and, perhaps, the secret to a more active or selective catalyst. A. New Transformations Catalysts make possible the chemically impossible. Thus, a majority of the discussion focused on which reactions are currently impossible to conduct and should be a priority for catalyst development in the future. General areas in which the catalysis group felt that new transformations would emerge included:

• Oxidation • Nitrogen functionalization • Hydrocarbon conversion • New polymerizations and oligomerizations • New bond-constructions for fine chemicals • New stereoselective reactions

These reactions could be conducted with homogenous catalysts, heterogeneous catalysts, or systems that are a hybrid of these traditional distinctions. Of course, the types of transformations also overlap with each other. For example, new hydrocarbon conversions could include oxidations and new polymerizations may involve control of stereochemistry. 1. Oxidation Oxidations with air belong to the oldest known chemistry, but even now are often the least selective. Oxidation catalysts should use inexpensive, readily available and environmentally benign oxidants for new transformations. Efforts to use alternate “green oxidants” like air and O2 will be important toward this end. Oxidation of alkanes is a well-known problem, but oxidation of aromatics to phenols, of benzylic positions to carboxylic acids, or selective oxidation to an alcohol or aldehyde using dioxygen would be important advances. Perhaps new insights on bioinorganic oxidation catalysts such as P450 and methane monooxygenase will lead to a different synthetic approach to hydrocarbon oxidation using dioxygen. Indeed, two groups have recently used model compounds for non-heme iron as a means to conduct among the most efficient oxidations of olefins that are known. 2. Nitrogen Functionalization An obvious goal for dinitrogen chemistry is the discovery of catalysts for the formation of ammonia at lower temperatures. However, the use of nitrogen for synthesis of other amines


28

has attracted less attention, but would be equally important. One paper has described the formation of arylamines from dinitrogen, although with stoichiometric amounts of alkali metal reductant.41 Toward this goal the development and understanding of the reactivity of complexes derived from dinitrogen remains as important a goal as it was thirty years ago. This statement applied to heterogeneous as well as homogeneous systems. In fact, improved heterogeneous catalysts for ammonia synthesis are emerging.42 Perhaps improvements in the understand of how nitrogenase converts N2, H+ and electrons into NH3 will assist in improved catalytic systems applicable to synthesis. Imagine a day when farmers could have their own small ammonia generators. 3. Hydrocarbon conversion Tremendous economic and environmental benefits would be realized by the direct utilization of hydrocarbons as feedstocks for the synthesis of value-added chemicals. Such technology would reduce energy costs and waste streams in the front end of chemical production and could provide liquid organic fuel that is easier to transport than gaseous natural gas. Selective conversion of alkanes to teminally functionalized products such as primary amines, alcohols and α-olefins and the regio- and chemoselective conversion of arenes to phenols and anilines is the major goal for direct conversion of hydrocarbons to chemical building blocks. The selective cleavage of terminal C-H bonds of alkanes provides the entry into terminal functionalization of alkanes. Development of these reactions requires a number of creative approaches. New reactivity of transition metal complexes such as oxo and dioxygen species is required for conversions. Alternatively, the creative selection of reagents that functionalize hydrocarbons is required. For example, N2O – a byproduct of current chemical processes – hydroxylamines, and related reagents possessing a thermodynamic driving forces for functionalization could lead to novel functionalization processes. Finally, selective reactions with alkyl or aryl C-H bonds in functionalized molecules could lead to novel synthetic methods. One can imagine using these reactions to modify a terminal alkyl group at a late stage in a synthetic sequence. Some progress has been made recently in this direction.43,44 The late-stage use of olefin metathesis has transformed strategies in synthetic organic chemistry.

H

HHH O2

H

OHHH

H

HHH

H

HHH

H

HHH

H

OHHH

H

OHHH

catalyst

4. New Polymerization and Oligomerization Reactions. Well-defined olefin polymerization initiators that tolerate monomer functionalities will make it possible to produce materials with unique properties from cheap and readily available starting materials. In the area of commodity plastics, the possibility of introducing complex molecules within the polymer backbone will give way to “smart” materials that could sense the environment and provide an adequate response. The controlled polymerization of non-petroleum based monomers using organometallic or inorganic complexes will generate


29

biodegradable and biocompatible materials. In particular, living synthesis of polyoxygenates will provide opportunities for designing interface materials for biomedical applications. Catalysts that control monomer addition to specify polymer architecture will provide materials with novel solid state and rheological properties. In the chemical industry, oligomerization reactions are used to produce basic commodity starting materials. However, these reactions produce statistical mixtures of chain lengths and therefore generate large quantities of undesirable products. New catalysts that can generate a specific chain length are needed. Ligands that confine the catalytic site within a restricted environment may provide the entry into such catalytic systems. 5. Fine Chemical Production Fine chemicals are generally produced by multistep synthetic schemes. Living organisms do the same, but their synthesis is catalyzed at nearly every step to produce exquisite selectivity and fast rates. One goal for catalysis is to enable the synthesis of complex materials by a series of catalytic processes that generate no waste, use no protective groups, occur in one pot, and proceed with rapid rates. Approaching this goal provides endless opportunities for catalysis in the synthesis of fine chemicals for future decades. An explosion of catalysis in this arena has already begun. The scope of highly enantioselective hydrogenations has expanded, new methods for aromatic substitution have been developed and made efficient, new enantioselective bond constructions have been invented, and methods to control regio and diastereoselectivity have begun to emerge.

terminal-selectivecatalyst

OH

enantioselectivecatalyst

OH

pharmaceuticals polymer additivesdetergents

Fine chemical synthesis provides high value added to materials, making it more competitive to use larger amounts of catalyst than in the synthesis of commodity chemicals. Many issues of stereo and regiocontrol can be influenced by a catalyst. Five of many opportunities in fine chemical synthesis include 1) regioselective bond formation at arenes that eliminates halogen byproducts and halogenation steps, 2) Enantioseletive formation of quaternary carbons, particularly by C-C bond-formation, 3) Catalytic control of diasteroselectivity, particularly to invert the selectivity relative to that of uncatalyzed reactions, 4) enantioselective variants of classic uncatalyzed reactions, 5) regio and enantioselective additions to olefins. 6. Specific Challenges for Heterogeneous Catalysis The outstanding challenges in heterogeneous catalysis are, among others, lean DeNOx catalysis (for mobile combustion product remediation), selective oxidation of saturated hydrocarbons, selective hydrogenation of polyunsaturated molecules, enantioselective catalysis of fine chemical intermediates, and discovery of reactions involving the formation of classic functional groups. For example, chlorination (fluorination) of organics and


30

polymerization of inorganics remain important unsolved problems. Among the latter, for example, a better understanding of the synthesis of materials such as Si or GaN nanowires catalyzed by transition metals is needed B. New Mechanistic Principles Emerging catalytic processes provide new challenges for mechanistic chemists. Although catalyst discovery requires hours of trial and error, these attempts at discovery are by no means random. Instead, they are guided by previous mechanistic principles, in many cases uncovered by understanding previous catalytic processes. In some cases, mechanistic insight leads directly to improved catalysts or new processes. In other cases, the mechanistic principles provide a foundation for new discovery. Fundamental studies provide a lexicon of reactivity from which we select elementary reactions to generate new multistep catalytic processes. Some of the topics discussed by the catalysis subgroup for mechanistic study currently include:

• Structure, dynamics and reactivity of highly unsaturated metal complexes • New ligands that stabilizing transition metal reactive intermediates • Discovery of new elementary reactions • Understanding of how to control stereoselectivity • Delineating the mechanisms of bioinorganic enzyme intermediates • Identification of intermediates in heterogeneous catalysis • Understanding of the dynamics of heterogeneous catalytic intermediates • Understanding of catalytic events that occur under extreme temperatures and

pressures Highly unsaturated species are often intermediates in catalytic reactions from alkene polymerization to olefin metathesis to CH bond activation to cross coupling. The structure, dynamics, and reactivity of highly unsaturated species need to be explored. Furthermore, the steric and electronic roles of new ligand types in stabilizing these extremely reactive species offers opportunities for fundamental advances that would results from direct observation and study of these unsaturated intermediates. Many exciting new catalysts have cationic and highly electrophilic metal centers. These cationic, electronically unsaturated complexes generally interact with counterions, even the weakest coordinating anions. The strength of these interactions and the dynamics of ion pairs in controlling catalytic processes need detailed study. In addition, both neutral and cationic high oxidation state organometallic compounds such as Rh(V), Ir(V), Ru(IV), and Cu(III) are beginning to be recognized, but few of these reactive intermediates have been studied directly. Exploration of their chemistry will provide new insights into important catalytic reactions. New elementary reactions will lead to new catalytic processes, and new catalytic processes will uncover new elementary reactions. For example, Noyori’s catalysts for ketone hydrogenation deliver H2 by a new outer sphere process.45,46 Jacobsen’s asymmetric ring opening of epoxides occurs by a bimetallic mechanism with one metal as Lewis acid and one delivering the nucleophile.35 Aryl halide aminations involve new types of C-N reductive


31

elimination,47 and metal-catalyzed diborations occur by a new oxidative addition of boron-boron bonds.48,49 As an example of how these new reactions can lead to new catalytic chemistry, this new oxidative addition of diboron compounds studied in the context of diboration of alkynes49 led to the first terminal functionalization of alkanes.50 A few examples of currently unknown elementary reactions that would be important for catalyst discovery are olefin insertions into metal-nitrogen or metal-oxygen bonds, concerted insertion of the oxygen atom in a metal-oxo into an alkane C-H bond, insertion of oxygen into late transition-metal carbon bonds, oxidative addition of the N-N bond in hydrazines, or the N-O bond in hydroxylamines. Stereoselectivity lies at the heart of synthesis, but methods to predict and control this selectivity are primitive. Yet, new approaches to control enantioselectivity are being developed. The use of achiral ligands that have chiral conformations when coordinated to a metal51,52 can amplify the chirality of a smaller and less expensive chiral group. The importance and ability to exploit achiral additives is beginning to be appreciated.53 Chiral poisoning54 and chiral activation55 have led to new ways to use racemic ligands for enantioselective catalysis. Many of these approaches are based on the nonlinear effects outlined by Kagan.56 Even the types of ligands that are though to allow high selectivity are being rethought. The dogma of C2 symmetry has been broken, as P,N,57 phosphine/phosphite mixed donors58 have become some of the most selective ligands for certain enantioselective processes. Clearly, new privileged ligand structures, similar to BINAP, BINOL, and Jacobsen’s salen, will need to be developed to expand the scope of enantioselective reactions, while the new approaches to developing catalytic systems mentioned above should make for more cost-effective catalytic processes. Advances in heterogeneous catalysis depend upon the current progress in synthesis (particularly inorganic), electronic and atomic structure characterization, and theory. The interplay between reaction steps occurring at local catalytic sites and the dynamics of fluid and solid phases containing or surrounding the sites needs to be better understood. While reactivity of the localized site is controlled mostly by the chemical nature of the metallic, ionic, or non-metallic phases, the selectivity is affected to a large extent by the “secondary structure” supporting the active phase. The current lack of fundamental understanding of mechanisms of reactions catalyzed by solids is due to incomplete characterization of the intermediate complexes (i.e., the reacting species bound to the active phases). Recognition that the solid phase undergoes fast dynamic transformations during catalytic cycles is only recent. Advances in time-resolved spectroscopy and in situ characterization techniques are just now being extended to heterogenous catalytic systems. These types of studies should provide an active area of future research. The structure of the highly dispersed (nanostructured) catalytic phases both during growth (synthesis) and during their reactions is being accessed using synchrotron-based techniques (neutron or x-ray small angle scattering). Speciation of ionic sites with various electronic spectroscopies, particularly of sites undergoing redox cycles, is providing insight of value in understanding catalytic mechanisms. Reactions carried outside of the “usual” industrial range of 150-450C and 1-30 atm follow mechanisms not well understood. High-temperature oxidation of saturated hydrocarbons on


32

inorganic or metallic membranes, for example, contains elements of radical chemistry and surface chemistry that is not understood. Reactions carried out using superacidic solids instead of liquid acids have been, for the most part, impeded by lack of stability of the catalyst. Some metalloenzymes catalyze remarkable transformations, and efforts to understand their mechanism have been one focal point of bioinorganic chemistry. With the recent generation of new structural and mechanistic information, two approaches may allow catalysis inspired by metalloenzymes to influence synthetic chemistry. First the small-molecule complexes that mimic the activity of metalloenzymes may become active and selective enough to prepare fine and commodity chemicals. Of course, this objective has driven research on nitrogenase, P450, and methane monooxygenase for years. Understanding how to translate the enzymatic activity into small molecule catalysts is required to satisfy these objectives. Second, bioinorganic enzymes may be used to conduct transformations on unnatural substrates. Directed evolution59-62 should generate new enzymes that can operate under synthetic conditions, on unnatural substrates, with new selectivities, and perhaps even to catalyze unknown reactions. For example, soluble or supported enzymes could functionalize the terminal position of an alkyl group to generate terminal alcohols. Efficient catalysts for regioselective modification of aromatic systems could also be developed. Such catalysts could mimic the regioselectivity of an enzyme like phenylalanine hydroxylase, but without the need for recognition of the carboxy and amino functionality of phenylalanine. The interface of catalysis and environmental chemistry may be a particularly fruitful area for bioinorganic catalysis. In fact, remediation of the Alaskan coast after the Valdez spill was aided by the action of organisms that oxidize hydrocarbons. C. New Approaches to Catalyst Discovery and Development 1. New Solvents Reaction Media

• “Green” solvents (water, fluorous, supercritical CO2, ionic liquids) • Understanding the behavior of catalysts and reaction mechanisms in these

solvents • New combinations of solvents that provide advantages such as biphasic or

triphasic reactivity, control of polarity, supercritical conditions, etc. The environmental implications of reactions and chemical processes are becoming increasingly important. Within this realm, questions of atom economy, by-products and solvent utilization and reclamation have been raised. These concerns lie at the heart of “green chemistry” and chemically benign synthesis and processing. With regard to solvents, aqueous media and supercritical fluids hold great promise for the reduction of waste in chemical synthesis and processing. Successes in aqueous media such as Rhone-Poulenc’s hydroformylation system based on a highly water soluble sulfonated triphenylphosphine rhodium catalyst63,64 and polymerization catalysis in super-critical CO2 (scCO2)65 augur well for the future. New ligand structures displaying solubility in aqueous media, new solvent media, or miscibility with CO2 need to be developed, synthesized, and studied.


33

Ionic liquids, which are the class of low melting salts, are another reaction medium that holds promise for catalytic processes in the future. Recent examples include imidazolium salts. Ionic liquids may prove particularly valuable for oxidation-reduction reactions and other transformations involving charged species or separation of non-polar organics from the catalyst-solvent mixture. The combination of scCO2 and ionic liquids also holds considerable promise as a solvent system where the density and polarity can be tuned based on CO2 expansion of the ionic liquid. 2. Homogeneous/Heterogeneous Interface

• Controlled production of clusters/colloids with specific sizes and compositions • New catalytic applications for nanosized clusters • New support strategies for heterogenizing homogeneous catalysts • New support strategies for nanosized clusters • Studying the transition region from molecular to bulk properties

Although catalysts are generally classified as homogeneous or heterogeneous, and the communities developing these two types are systems traditionally do not overlap, future opportunities may lie at the interface of these two areas. The ability to produce nanosized (1-100 nm) metal clusters with specific sizes and compositions (in the case of multimetallic clusters) would mimic the control of homogeneous catalysts, but may provide reactivity and separations advantages of heterogeneous catalysts. Nanosized clusters have been shown to possess interesting catalytic properties, but much more work in this area needs to be done particularly on size specific reactions. The development of new support strategies for converting homogeneous catalysts into heterogeneous catalysts is also needed, especially for catalytic reactions involving CO where metal leaching is a serious problem. Supports for nanosized clusters is also an area where additional research is needed. Finally, gaining a firmer understanding of the transition from molecular to bulk properties in metal clusters and the relationship to catalytic properties is an area where additional research is certainly needed. 3. Theory

• Improved theoretical techniques for better studying larger and more complicated systems

• Closer coupling of theory and catalytic experimental results to provide better future guidance in designing new catalysts

• Use of theory in understanding heterogeneous catalysis

As computational methods continue to advance at a rapid pace and as their program packages become routinely available to synthetic chemists, computational chemistry will blend theory and experiment to provide a detailed understanding of reaction pathways and in catalyst design. Sophisticated advances in computational chemistry will assist in ligand design (electronic and steric), understanding solvent and counterion effects, and in predicting new catalytic reactions. But there is still considerable need for improvements in computational


34

methods. The ability to handle complex systems in reasonable times is clearly needed. The continued development of systems that combine quantum mechanical methods and molecular mechanics should address this limitation. Ab initio electronic structure calculation at the site level embedded into meso-scale and long-range atomic structure models are starting to yield realistic potentials suitable for molecular dynamics calculations of catalytic relevance. Effective core potentials for late transition metals are also making it possible to simulate reactions catalyzed by noble metal crystals. Overall, the discussion group felt that closer collaboration between experimentalists and theorists, perhaps in the same research group, should allow theory to make an increased impact on catalyst discovery and development. Just as today’s result leads to tomorrow’s experiment in typical purely experimental group working on catalysis, theory may progress such that today’s calculation could lead to tomorrow’s experiment in a project with a well-integrated experiment and theory component. 4. Combinatorial or High-Throughput Method The advances in synthesis and screening of organic molecules for biological function has led to analogous approaches toward the synthesis and screening of inorganic solids and inorganic complexes for catalytic function. These methods have led researchers to investigate new ligand classes that allow for rapid parallel or split-pool synthesis. In addition, miniaturization of solid phase synthesis has led to new methods for preparing and screening heterogeneous catalysts.66-68 In homogeneous catalysis a few studies have investigated the synthesis and screening of conventional ligands such as phosphines.69-71 In some cases, screening of complexes formed from commercial coordination compounds combined with commercial ligands has led to new catalytic processes.70,71 However, new ligand types based on peptide architectures have led to remarkably selective catalysts.72-75 Of course, the peptide structures allow for synthetic methods that have their origin in biological studies to be used in ligand preparation. Yet, these ligand structures have been applied, for the most part, to generate Lewis acid catalysts. Catalysts prepared by high-throughput synthetic methods for classic organometallic processes such as hydrogenation, hydroformylation and new reactions that would be analogous to these types of reactions have seen limited success. In these processes, redox reactions and reactive nucleophiles are involved, and these reactions and regents have not been used in catalytic reactions with ligands generated in a truly high-throughput fashion. Thus, new approaches to preparation of ligands for these types of reactions and new classes of ligands that could catalyze these reactions need to be developed. With this emerging, high-throughput synthesis and the need to evaluate and optimize many reaction parameters to generate highly active systems, analysis of sets of reactions is necessary. Thus, another forefront area is the development of methods for analysis of large numbers of reactions. Some methods have been developed that allow for analysis of activity,76,77 but methods that evaluate for selectivity are less well-developed, though the grown in this area is rapid.78-83 Moreover, the existing methods are instrument-intensive, and are, therefore, available only to a subset of research groups. Methods that can be used by the general community need to be discovered and made general and reliable. 5. Ligand Design

• Modular ligands


35

• Shape selecting architectures • New reaction environments • New metallic clusters

An overriding theme in the design in catalysts is clever ligand design. One rhodium complex reacts differently from another because of the architecture and electronic properties of the ligands. In the past, monophosphines gave way to bisphosphines, cyclopentadiene to peralkyl cyclopentadienes, C2-symmetric ligands to C1-ligands, and arylphosphines to heterocyclic carbenes. As described above, the advent of screening methodologies should allow one to identify new catalysts from catalyst libraries that must be based on modular ligands prepared by simple, reliable reactions such as substitutions and condensations. New ligand architectures that that provide shape selection and that create new reaction environments provide alternative or complementary alternatives. Catalysts encapsulated in dendrimers, polypeptides, zeolites or imprinted polymers can provide selectivities that compliment or enhance the selectivities observed without this encapsulation. New classes of heterogeneous catalysts are emerging that are based on inorganic complexes or metallic clusters that are stabilized by designed cage structures. Ship-in-the-bottle synthesis of metal-containing calixarenes, new polyoxometallates, silsesquioxanes and even new zeolites and molecular sieves are providing a natural linkage between homogeneous and heterogeneous catalysis. IV. CHALLENGES BEYOND TODAY A. Catalyst Evolution As discussed in the bioinorganic catalysis section above, genetic techniques that allow for directed evolution may be used to create new metalloenzymes that catalyze related, but new abiological reactions. Biocatalysis is progressing from phenomenological enzyme catalysis to metalloproteins and designed metal-containing polymeric catalysts that will extend the accessible range of conditions and reaction media while maintaining enzyme-like specificity. Alternatively, one could imagine artificial evolution of purely chemical systems. Methods for synthesis and amplification of chemical systems have been published recently,84 and one could imagine using such methods for evolving catalysts. Some day, we may conduct the types of screening and amplification used to modify and select enzymes for preparing and optimizing homogeneous or heterogeneous catalysts with purely artificial chemical architectures. B. Programmable Tandem Reactions (or Reaction Networks) Emerging mechanistic understanding of catalysis has made imaginable the coordination of multiple catalysts to synthesize complex molecules from simple molecular building blocks. This idea is not new; the Wacker process uses copper to react with O2 and form water and palladium to activate an olefin toward attack by the water. In the Monsanto acetic acid synthesis catalytic HI generates methyl iodide from methanol, and the methyl iodide is used by the rhodium (now iridium) catalyst to form acetic acid. However, few other systems with two or more catalyst components that serve separate functions have been developed. This general approach could be used to allow important reactions that are hard to effect with a


36

single metal complex to occur. The simplest generic diagram of this concept is shown below. Substrate A is reacts with catalyst I to give product B, and product B then is transformed by the second catalyst, II, to the final product, C. The action of a third catalyst on C is easily envisioned.

A

B CI II

Such schemes offer new opportunities for reaction design. Such a multistage catalytic reaction may lead to fewer purification steps. Moreover, species with limited lifetimes, such as vinyl amine or vinyl alcohol85 are not isolated and are used immediately. In this way, complex polymer structures can be generated using a single monomer source. Ultimately, the creation of complex reaction cycles that can be programmed by the composition of the catalyst mixture may produce different product distributions from only a few starting materials. A wide range of compatible sites in such a multicomponent system challenges one to coordinate the function of homogeneous, heterogeneous and biologically inspired catalysts. References for Chapter 4 (1) Roelen, O. 1938, DRP 849548. (2) Roelen Angew. Chem. 1948, 60, 62. (3) Hallman, P. S.; Evans, D.; Osborn, J. A.; Wilkinso.G Chem. Commun. 1967, 305. (4) Osborn, J. A.; Wilkinso.G; Young, J. F. Chem. Commun. 1965, 17-&. (5) Ziegler, K. Adv. Organomet. Chem. 1968, 6, 1. (6) Natta, G. Scientific American 1961, 205, 33. (7) Brintzinger, H. H.; Fischer, D.; Mulhaupt, R.; Rieger, B.; Waymouth, R. M. Angew.

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Chapter 5 – Detailed Report on Bioinorganic Chemistry Discussion Leader: Vickie DeRose Participants: Andy Borovik Brian Hoffman Dick Holm Steve Lippard Yi Lu Tom Meade Larry Que Hilary Godwin (in absentia) [J. Espenson, R. Eisenberg, Mahdi Abu- Ohmar, Tom Spiro were present for part of the second session.] I. BIOINORGANIC CHEMISTRY: SUMMARY Bioinorganic chemistry is a vibrant and dynamic field that heavily impacts developments in other fields. Its important successes include understanding metal-ion catalysis in enzymes, coordination chemistry of metals involved in imaging, diagnostics and therapeutics, and synthesis of small models. Current and future frontier research build on these successes and also on new discoveries of the past decade that have opened up entirely new areas. As advances in genetics, structural biology, spectroscopy and synthesis have bolstered recent efforts, new tools in bioinformatics, genomics, and nanotechnology will continue to advance the frontiers of the field. Bioinorganic chemistry is an excellent model of collaborative science that both contributes to and benefits from other fields. The educational component of this field is exceptional. II. BIOINORGANIC CHEMISTRY FOR THE COMING DECADE A. Recent Major Accomplishments

1. Structure and Function of Key Metalloenzymes

• New structures: cytochrome oxidase, nitrogenase, methane monooxygenase, hydrogenase, sulfite reductase

• Spectroscopy of resting states, intermediates • Gene expression systems

Figure 5.1 X-ray crystal structure of Methane Monooxygenase determined by Rosenzweig et al.


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The last ten years have seen extraordinary advances in obtaining resting-state structures of important metalloproteins using X-ray crystallography (Figure 5.1). These pictures of active sites are augmented by spectroscopic studies of trapped intermediates, and results from site-directed mutagenesis studies. The gene sequences for important enzymes have been cloned and sequenced, often with operons that include regulatory domains as well as the protein-coding sequences. This information has laid the groundwork critical to understanding the molecular mechanisms of a fundamental class of biocatalysts that perform transformations of potential economic value. 2. Biomimetic Chemistry

• Metal catalyzed hydrolysis • Models of the nitrogenase active site • Oxygen activation

Strong success has been achieved in synthesizing metal coordination compounds that mimic the structure and spectroscopic properties of important metal centers found in biological systems (Figure 5.2). These studies lead to an understanding of the requirements for forming catalytic sites in biology, and lead the way to creating new man-made catalysts. Great strides have been made in the past decade with respect to the development of structural and functional models of metalloenzymes that catalyze hydrolysis, nitrogen fixation, oxygen activation, and hydrocarbon oxidation. In the metallohydrolase area, the principles by which metal centers activate water to carry out amide and phosphate ester hydrolysis have been elucidated (J. Chin, S. J. Lippard). In the nitrogen fixation area, MoFeS clusters with stoichiometries approaching that of the FeMo cofactor in nitrogenase have been characterized (R. H. Holm, D.Coucouvanis) and some of these clusters can effect N-N bond cleavage of hydrazines (D. Coucouvanis). Furthermore N-N bond cleavage of dinitrogen has also been demonstrated for a tris(imido)molybdenum(III) complex (C. Cummins). In the oxygen activation area, there has been significant progress in understanding the chemistry of dicopper(I) centers. Crystal structures of two distinct dioxygen adducts have been obtained, one with µ-1,2-peroxo coordination (K. D. Karlin) and the other with µ-2,2-peroxo binding (N. Kitajima). Other dicopper(I) complexes react with O2 to cleave the O-O bond and afford high-valent CuIII

2(µ-O)2 complexes (W. B. Tolman, T. D. P. Stack, S. Itoh, M. Suzuki). In several of these cases, the O-O cleavage is reversible. Thus, not only can the O-O bond be activated and cleaved at dicopper centers, it can also be re-formed. Comparable progress has also been made in modeling oxygen activation at diiron centers. Crystal structures of three dioxygen adducts with µ-1,2-peroxo bridges have been reported (M. Suzuki, L. Que, S. J. Lippard). Also examples of Fe(III)Fe(IV) complexes derived from the reactions of diiron centers with O2 or H2O2 have also been found (L. Que, S. J. Lippard), providing models for high-valent intermediates for nonheme diiron enzymes. In one case, an Fe(III)Fe(IV) complex with an Fe2(µ-O)2

core has been crystallographically characterized (L.


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Que). At a recent international bioinorganic conference, the characterization of a diiron(IV) complex was presented (L. Que), which provides the synthetic precedent for the putative Fe2(µ-O)2

core of the diiron(IV) intermediate Q in the catalytic cycle of methane monooxygenase inspired by biological systems. 3. Chemistry of Bioinorganic Pharmaceuticals

• Anticancer therapeutics (Pt) • Contrast agents for imaging and diagnostics (Gd, Tc) • Metal pharmaceuticals as enzyme inhibitors

Fundamental studies of metal coordination properties have led to advances in the use of inorganic compounds as both therapeutic and and diagnostic agents.

Figure 5.2 Some successful bioinorganic models.


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3.1 Metal complexes as antitumor agents Cisplatin, cis-diamminedichloroplatinum(II) and carboplatin, cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II), continue in widespread use as anticancer drugs. From detailed knowledge of how cisplatin binds its target in the cell, DNA, and how the resulting

adducts are processed (Figure 5.3) has come a rational design of new chemotherapeutic protocols that are now in a phase I clinical trial. Cisplatin analogues that can be administered orally and/or are active against cisplatin resistant tumors are now in the clinic. Multiplatinum complexes have been devised that work by a different mechanism and may be able to treat cancers for which cisplatin has not been very successful.

3.2 Metal complexes in imaging Coordination chemistry is providing entirely new generations of magnetic resonance (MR) and positron emission tomography (PET) contrast agents that report on anatomical and physiological processes (function) of intact animals and humans in the form of acquired 3D images. Metal complexes with favorable characteristics have been designed for MR imaging [Gd (T1), Fe (T2)] and PET (Tc, Cu). Specific advances include:

• cardiovascular imaging Gadolinium(III) bound to human serum albumin (HAS) allows this MR contrast ion

to reside in the blood long enough to provide high resolution images of the heart for diagnostic purposes.

• enzymatically activated MR contrast agents provide in vivo images of gene expression. Recent advances in the synthesis of new coordination complexes now allows the

synthesis of MR contrast agents that are enzymatically activated in vivo to conditionally enhance image intensity. When the access of Gd3+ to bulk water is limited, there is little effect on MR imaging but now agents designed to expose the Gd3+ by enzymatic processing in the body can be reliable markers for regions of enzyme activity. In these internally-activated contrast agents, covalently attached carbohydrate groups prevent Gd3+ exposure to water. When these gropus are lopped

Figure 5.3 Proposed mechanism for action of cisplatin.


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away from the macrocylic framework holding the Gd3+ by β-galactosidase. • MR imaging of secondary messengers in neuronal signaling

Ca2+ activated MR contrast agents detect in vivo Ca2+ concentration. Ca2+ is an important intracellular secondary messenger of signal transduction. Changes in the cytosolic concentration of Ca2+ trigger changes in cellular metabolism and are responsible for cell signaling and regulation. Advances in optical microscopy techniques and improvements in fluorescent dyes capable of measuring Ca2+ concentration have added greatly to the understanding of the critical role this ion plays in cellular and neuronal biology.

• PET imaging New contrast agents based on Tc and Cu coupled with rapidly developing

instrumentation is providing vivid images of both the stucture and function of organs in animals and humans. .

3.3 Bioinorganic Pharmaceuticals/Metal Complexes as Enzyme Inhibitors Transition metal complexes have long been known for therapeutic effects while the mechanisms of action are not understood. Advances in elucidating molecular structures of protein and enzymatic targets has led to a rational approach to the design and synthesis of new drugs. In addition to the Pt-anticancer drugs, many inorganic complexes are used in the therapeutic treatment of diseases, including: Hyperbilirubinemia (Sn, Zn), Nitric Oxide Transduction (enzyme inhibition) (Zn, Sn, Fe, Cu), Hypertension (enzyme inhibition) (Cu, Zn, Ge, Sb) Protease inhibitors (Co, Ti, Cu), Neurological effectors (Al, Fe, Zn, Pt, Sn), Arthritis (Au, Cu, Fe), Antiviral (enzyme inhibition) (W, Sn, V, Cu, Ni, Pd, Cu, Pd), and Hypochromic anemia (Fe). It must be emphasized that basic research of coordination complexes and enzyme active sites has led to much of the progress in these areas. 4. Long-range Electron Transfer

• Tunneling timescales (Ru-modified Cyt c) and pathways • Donor-acceptor partners

A fundamental understanding of long-range biological electron transfer is a triumph of the recent past. While the theory of these basic process had been formulated in the work of Marcus and others, and its quantum mechanical correlates, the connection between these theories and the actual process of electron transfer in biomolecules, both proteins and nucleic acids, presented a major challenge that has been addressed with great success. 5. De Novo Design in Metalloproteins and Peptides Successes have begun in two main areas of de novo design. Accomplishments in the last decade in the redesign of metalloprotein active sites are based on advances in protein expression methods, computer-based predictions of structural changes, and synchrotron access for protein crystallography. Based on these advances, tremendous progress has been made in this area. For


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example, several metal-binding sites, such as heme, zinc, binuclear iron centers and Fe-S clusters have been designed into de novo designed protein scaffolds such as four -helical bundles. Native protein scaffolds such as Greek Key -barrel have also been used for the design and engineering of zinc, copper, manganese, heme and non-heme iron (including Fe-S cluster) proteins. Furthermore, metal-binding sites have been also designed using peptides consisting of key structural elements for the formation of the sites such as Fe-S clusters and blue copper center. Complementary to these rational design approaches, new methods for selection and directed evolution of proteins in the laboratory have also been developed and resulted in metalloproteins with either improved function or new functions. As with the redesign of protein active sites, computer modeling is an integral component of this work. 6. Integration of Theory Coupling density functional theory calculations with experimental results has made a large impact on our understanding of the underlying principles of the extraordinary electronic and magnetic properties of metal centers in proteins. Molecular dynamics calculations have increased our understanding of the static and dynamic behavior of biopolymers including both proteins and DNA. Advances in the theoretical treatments of solvation have influenced and benefited {does this refer to DFT/MD or static/dynamic or proteins/DNA?]. 7. Influence of Bioinorganic Chemistry on Other Fields

• Zn-fingers and gene expression • Cu-SOD and disease • NO chemistry

Fundamental bioinorganic investigations have had broad impact in the areas of development, regulation, and disease. Examples include the ubiquitous Zn-finger motif, which is now known to have widespread importance in gene expression and regulation the connection between Cu/Zn superoxide dismutase and genetic mutations leading to Parkinson’s disease, and the discovery of nitric oxide as a central biological signaling agent with relationship to vasculature disease, the immune response and neuronal development. 8. New Discoveries That Lay the Basis for Future Research

• Role of metal homeostasis on disease • Biosynthesis of metal centers (i.e. urease) • Metals and prion disease • Metals and RNA (ribozymes)

From within the subdiscipline and from disciplines outside of chemistry, groundwork for the future hot topics in bioinorganic chemistry was laid in the last decade with the discoveries of biosynthetic pathways for metal centers, the influence of metals on complex nucleic acid structures and on RNA catalysis, hints at the complexity of biological metal sensing and


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transduction involved in controlling metal levels in vivo, and the most recent discovery that prion-type diseases may involve coordinated metal ions. The portfolio of bioinorganic research targets has increased over ten-fold with these discoveries from outside areas. B. At the Frontiers in Bioinorganic Chemistry 1. Biocatalysis

• Manipulation of small molecules N2, CO, O2, H2O, CH4, NO • Multi-e- reactions • Hydrolytic reactions • Relationship to green chemistries

An important and necessary development from the significant efforts in modeling how metal centers in biology work is the continuing design of metal complexes, either biomimetic or bio-inspired, that can catalyze transformations of interest to the chemical industry. Because of their biological roots, such catalysts have the potential of carrying out reactions under conditions that require low energy input and have significantly lower environmental impact, thereby giving rise to a generation of “green” catalysts. An example of a bio-inspired oxidation catalyst is a recently reported mononuclear chiral iron complex that reacts with H2O2 to catalyze the enantioselective cis-dihydroxylation of olefins (L. Que). Such a catalyst carries out the same transformation as the much more toxic OsO4 reagent and is inspired by the cis-dihydroxylation reactivity of arene degrading Rieske dioxygenases, which have mononuclear iron active sites. 2. Design and Synthesis of Functional Models

• New coordination chemistries • Unique functionalities (H-bonding, radicals) • Peptidomimetics • Engineering protein sites

Chemists aspire to understand natural phenomena by attempting to recreate them with as much fidelity as possible. In bioinorganic chemistry, the two broad categories of phenomena are active site structure and function, which usually is reactivity. In this way, the principles of structure stabilization and the factors essential to biological substrate reactivity may be revealed. Considerable progress has been made in e.g., iron-sulfur proteins and enzymes, molybdenum and tungsten enzymes, heme oxygenases and oxidases, and certain hydrolytic enzymes. Because of the increasing ability to interrogate protein-bound sites by spectroscopic methods with increasing information yield, targets of opportunity susceptible to the biomimetic approach must be chosen carefully. There remain, however, numerous problems to which this “minimalistic” approach can be applied with profit. These include, prominently, enzymes that catalyze multi-electron transformations such as all molybdoenzymes (excluding nitrogenase), hydrogenase, carbon monoxide dehydrogenase, and methane monooxygenase (2e-); Kodachrome oxidase (4e-); and nitrogenase, nitrite reductase, and sulfite reductase (6e-). It is to be emphasized that the chemist


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has not yet learned to manipulate substrates of these enzymes in the manner of enzymic reactions. Hence, biomimetic inorganic chemistry is a logical place to disclose the fundamental redox reactions of molecules such as H2, N2, CO, CH4, NO, and O2. [latter may be included in biocatalysis section] 3. Theoretical Analysis of Metalloenzyme Reaction Pathways As computational approaches become more efficient, mechanistic questions can be attacked by theoretical methods that include mixed quantum-mechanical and classical approaches. These, in combination with adequate solvation models, allow calculations of transition-state models that include hydrogen bonding and other effects not well modeled utilizing only the classical approach. Theoretical methods continue to be an important research tool. 4. Design and Synthesis of Functional Models The development of functional complexes that mimic chemical transformation found in nature continues to be an area of intense interest in bioinorganic chemistry. Examples encompass the activation of small molecules, such as dioxygen, carbon monoxide and dinitrogen. Two general approaches are used in designing synthetic metal complexes of this type: biomimetic and bioinspired. A biomimetic approach utilizes the exact structural elements found at the active site of metalloproteins to reproduce function. These efforts target complexes that emulate the primary coordination sphere of active site metal ions. A bioinspired approach uses some, but not all, of the structural properties of the active site to design new complexes with important functional properties. Incorporation of key structural elements into synthetic systems, particularly those in the secondary coordination sphere involving non-covalent interactions, is leading to a more complete understanding of structure/function relationships that are found in biomolecules. An example of this approach is the use of intramolecular hydrogen bonding to stabilized monomeric iron complexes with terminal oxo ligands derived from dioxygen (Borovik). Of the two broad phenomenological categories above, the creation of functional models carries the greater imperative. This work requires extensive use and possibly further extension of the principles of coordination chemistry. One example of new ligand types found in biology are stable radicals (attached to metals) that are directly implicated in the catalytic mechanism. There can be no doubt this general family of ligands and complexes will grow and new synthetic methods develop and further examples of radical -mediated enzymic reaction are discovered. A further area of assured significance in the future is “peptidomimetics”. Here peptides are designed with appropriate structural elements to stabilize natural metal-binding environments with physiological ligands. Further, residues can be varied, analogous to site-directed mutagenesis, so as to reveal their roles in structure and catalysis. Given the accelerating advances in peptide synthesis (including the concept of de novo design), protein structures, and protein dynamics, peptidomimetics is poised to play a prominent role in the next decade of biomimetic inorganic chemistry.


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5. Metal Site Biosynthesis

• Mechanisms of biological cluster assembly One of the major unsolved problems in metallobiochemistry is the elucidation of biosynthetic pathways leading to mononuclear and polynuclear metal sites. This is truly an interdisciplinary problem that will require contributions from geneticists, biochemists, biophysicists, and inorganic chemists. Almost nothing is known about the mechanism of metal ion insertion and the means of cluster formation in proteins. Substantial progress is being made on several fronts, e.g., the binuclear site of urease and the cofactor clusters of nitrogenase. Yet much remains. The role of the inorganic chemist surely will be to discover new reactions leading to biological coordination units and to demonstrate new structures relevant to protein-bound metal sites. The problem of metal site biosynthesis promulgates a forefront area in inorganic synthesis. 6. Metal Trafficking

• Chaperones and insertases • Disease states

Understanding how metals are regulated and trafficked in cells requires the marriage of bioinorganic coordination chemistries, in-situ spectroscopies, X-ray crystallography, and molecular and cellular biology. The challenges of tracing metal ion pathways towards their fates in metalloenzymes (see above) or disposal as toxic agents will continue to require the cutting edge of all areas of chemistry, and connects inorganic chemistry with the overarching area of ‘biocomplexity.’ 7. Electron Transfer The study of biological electron transfer (ET) has tended in two parallel directions, with one being the examination of ET between two redox centers within a single macromolecule, often with a second center having been introduced synthetically, the other being the study of ET between donor-acceptor partners. The future will bring major efforts in both directions. In the first, a key focus likely will be on the role of ET between naturally occurring redox centers in proteins/enzymes that contain multiple centers as a conduit to carry electrons between the site of electron entry/exit on the protein surface and the enzymic active site. The second will include the characterization of the interactions between strongly-interacting partners, but will accentuate the dynamics of docking and recognition of more weakly interacting ones. A third and emerging theme will be to design ways to utilize long-range ET to photoinitiate enzymatic redox reactions and to study their reaction intermediates. 8. Metals in Medicine The primary barrier to the exploitation of new imaging modalities for basic biological research and in clinical settings remains the design and synthesis of new coordination complexes as


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contrast agents. MR, PET, and traditional radiopharmacutical imaging modalities are undergoing dramatic changes by the advance of new technologies. Modern optical microscopy techniques, combined with fluorescent indicator compounds, have revolutionized studies of biological structure, function and development by allowing the physiology of intact cells and tissues to be assayed. However, light-based techniques, ranging from video-microscopy to laser scanning confocal microscopy, work best in the outermost 100 µm of a biological tissue due to light scattering and uncorrected optical aberrations.

• MRI of biological structures offers an alternative to light microscopy that can circumvent these limitations and analyses demonstrate the feasibility of true three-dimensional MR imaging at cellular resolution (~ 10 µm). In order to exploit the power of MRI for biological (and ultimately clinical studies), new contrast agents must be designed and tested that report on structure and function (i.e. gene expression). See Figure 5.4.

Figure 5.4 Schematic representation of an enzyme-activated MR contrast agent. A. diagram representing the site-specific placement of the galactopyranosyl ring on the tetraazamacrocycle (side view). Upon cleavage of the sugar residue by b-galactosidase (at red bond), an inner sphere coordination site of the Gd3+ ion becomes more accessible to water. B. Space-filling molecular model (top view, from above the sugar residue) of the complex before (right) and after cleavage by the β-gal (left), illustrating the increased accessibility of the Gd3+ ion (magenta) upon cleavage.


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The challenge for the development of new agents is a fundamental structural analysis of how to modify the chelate structures to accommodate targeting groups such as peptides and DNA and to improve image contrast and delivery. 9. Metalloenzymes with New Activities

• Directed evolution • Active site engineering

By a recent estimate, metalloproteins account for approximately half of all proteins in biological systems. They play key roles in all almost every aspect of biology. The design and engineering of novel metalloproteins with desired structural and functional properties remains one of the most exciting research areas. Protein design is not only an ultimate test of our knowledge of metalloproteins, but also can result in new metalloproteins with improved or even unprecedented properties for biotechnological and pharmaceutical applications that benefit the society. In the next decade, the development of new computer algorithms for rational design, and innovative directed evolution/selection strategies will assist protein design. We will also see more studies that combine both rational and evolution approaches. 10. Metals and Nucleic Acids

• Coordination modes • Ribozyme mechanisms

The importance of nucleic acids in a myriad of cell functions coupled to the relative youth of the field of nucleic acid structural biology make this a forefront field in bioinorganic chemistry. It is clear that metal ions are intimately involved with the structures and chemical functions of nucleic acids, including both RNA and DNA. Recent crystal structures of complex RNA molecules, from ribozymes to ribosomes, show localized metals whose influence on solution-state structure and function has yet to be determined. Spectroscopic and synthetic endeavors in measuring and modeling metal-nucleic interactions are current ‘hot topics’ emphasized in every national and international meeting. Based on groundwork currently being obtained, future work is expected to include design of metal sites that may stabilize unique structures, including supramolecular lattices, and also create new catalytic functions. 11. Neurochemistry – Current Topics and Future Challenges Metalloneurochemistry: An Emerging Area of Bioinorganic Chemistry

“…Of the areas at the interface between inorganic chemistry and biology that remain to be explored, the role of metal ions in neuroscience is perhaps the most prominent. Bioinorganic chemists have been attracted historically to systems involving transition metal ions because of their valuable magnetic and spectroscopic properties. Despite the preponderance of Na+, K+, Mg2+ and Ca2+ in biological processes, the inorganic


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chemistry community has often ignored these metal ions because they lack the electronic and magnetic properties of their d-block counterparts. In a similar manner, neuroscientists have focused on group 1 and 2 metal ions and, until recently, have dismissed transition metals such as Mn, Fe, Cu, and Zn as inconsequential trace elements in the central nervous system [see Figure 5.5]. By combining the ability of bioinorganic chemists to evaluate the properties of metal ions with that of neuroscientists to explore the physiology of the nervous system, a powerful new alliance could emerge for understanding such complex processes as neurotransmission and synaptic plasticity. An important consequence would be to uncover the causes of, and develop treatments for, neurodegenerative disease….” From: Coordination Chemistry for the Neurosciences. Shawn C. Burdette and Stephen J. Lippard, Coord. Chem. Rev., 216-217, 333-361 (2001).

Figure 5.5 Hippocampal brain slice from rat stained with Zinpyr-1 showing vesicular zinc in CA3 nerve terminals; photo courtesy of Dr. Chris Frederickson, NeuroBioTex.

Specific topics that are currently being explored are: • the role of zinc in vesicles housed in the presynaptic nerve terminals of specific cells in

the hippocampus, the center of learning and memory in the brain; • the coordination chemistry that leads to the selective passage of ions through channels

and pumps • the role of nitric oxide as a retrograde messenger in the postsynaptic terminals of the

brain; • the role(s) of metal ions in diseases that arise from mutated or misfolded proteins,

including Alzheimer’s, prion disease, and ALS.

To meet these new challenges, some novel tools have to be developed for studying specific problems. For example, there is currently no good way to monitor where NO is generated and


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how far it migrates in brain tissue. Soluble sensors for in vivo use would greatly facilitate investigations of this problem. These sensors could be designed to take advantage of the coordinating ability of NO to transition metal complexes. Collaborations between inorganic chemists and neuroscientists are essential for significant progress to be made in the field of metalloneurochemistry. It is likely that, given the interest of young scientists in the brain and nervous systems, this topic will be of increasing significance in the coming decade. 12. Biological NO chemistry The medically critical production, regulation, and mode of action of nitric oxide as a signalling agent is an area of bioinorganic chemistry that encompasses structural biology, catalysis, and small-molecular chemistry. Bioinorganic mechanistic work on the key enzymes for NO production (NO synthase) and its target messenger agent, guanylate cyclase, remains a critical and provocative field that has relied heavily on past bioinorganic success stories in the field of heme enzymes. Laboratory investigations of the stability and reactivity of NO(x) compounds such as peroxynitrite, the toxic product used in cell defense systems, are also ongoing challenges that bridge inorganic and medicinal chemistries. 13. Sensors

• Coordination models for detecting metals in, ex vivo • Zn and Ca sensors for imaging metals in development, neurochemistry, disease states • Biomolecules as metal sensors • Bioinorganic systems as biosensors (ex. redox-based sensors)

Sensors for metal ions are an important focus of current research. These include chemosensors and biosensors. Synthetic calcium sensors have enjoyed the most success in monitoring in vivo calcium distributions during the cell growth and metabolism. Other chemosensors for zinc and mercury have also been synthesized and studied. Proteins, peptides, catalytic DNA/RNA have also been developed as biosensors for zinc, lead and copper. Culture cells that can sense different heavy metal ions have also be used. Metal ion sensors will be one of the most active areas of research in the next ten years, as they will be applied to environmental monitoring, clinical toxicology, neurological science, and wastes management. DNA oligonucleotides are a revolutionary addition to the sensor field. The study of energy and electron transfer processes through DNA duplexes and the development of DNA hybridization probes and electrochemical sensors have resulted in the incorporation of numerous transition-metal complexes into DNA oliognucleotides. These include ruthenium, osmium, iron, rhodium, and copper complexes.


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Ferrocene (Fc) and its derivatives are attractive electrochemical probes because of their stability and convenient synthetic chemistry. Fc-containing DNA oligonucleotides have been prepared by attaching ferrocenyl moieties to the 5’ termini through either solid phase synthesis using phosphoramidites or by reacting suitable ferrocenyl derivatives with end-functionalized oligonucleotides. Efforts have focused on ways to develop microsensors for electronically detecting nucleic acids where ferrocenyl derivatives are site-specifically incorporated into DNA oligonucleotides and are used as probes (Figure 5.6). . 14. Biomaterials

• Biomineralization • Biomimetic materials • Adhesion

Important hot areas of current research in biomaterials include:

• understanding the inorganic chemistry of adhesion in mollusks (Wilker) • using biomolecules, such as ferritin, as templates to synthesize new materials

(Douglas) • understanding the properties of shell growth in mollusks (Stuckey) • using inorganic materials in combination with biomolecules for the development of

new sensors (Mirkin) • using combinatorial methods to discover new metallobiomaterials (Belcher).

C. New Frontiers in Bioinorganic Chemistry 1. Inorganic chemistry of the Cell (‘Metallome’) Similar to the proteome and genome, determining the actual inorganic composition of cells under different expression conditions will be required to truly understand the influence of metals and other inorganic constituents in biological systems. New analytical methods and the fundamental methodology derived from nanotechnology will strongly impact determination of the ‘metallome’.

Figure 5.6 Electrode-based Biosensors based on ferrocene-linked DNA arrays


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2. Incorporating genomics into bioinorganic chemistry

• New metalloproteins with novel functions discovered from gene sequences • Chip detection of gene expression • Expression in response to (toxic) metals (Pb, Cd, Hg, Cr) • Metalloprotein expression related to development, disease, cell cycles • Metalloproteins involved in signaling • Metal ion homeostasis • New levels of biocomplexity

The Likely Impact of Genomics on Bioinorganic Chemistry The advent of gene chips, by which one can monitor gene expression, is likely to have a major impact on the field of bioinorganic chemistry. Because the area is so new, it is difficult to imagine exactly how this process will unfold, but a few examples will be useful to illustrate the concept. In the area of metals in medicine, it will become possible to compare the relative expression of specific genes in diseased and normal tissue from the same source, in the presence and absence of a particular metallopharmaceutical. From such information might come clues about the mechanism of action of the drug or new strategies for treatment. Another example pertains to the investigation of a cellular process such as apoptosis, or programmed cell death, which involves many metalloenzymes housed in the mitochondrion. The concerted expression or suppression of genes that encode these enzymes could allow one to understand the underlying bioinorganic chemistry of the process. A different application would be in the area of metalloregulation of gene expression, where genomics would enable new systems to be understood in response to a toxic metal ion such as lead in the environment. Finally, it should be noted that inorganic chemistry might play a role in the field of genomics by providing modified surfaces and new materials that could be used for the development of smarter, more efficient gene chips. 3. Biomimetic chemistry

• linked chemistry (sequential reactions, triggering) • scaffolds • combinatorial approaches • confined spaces • mesoporous solids, vesicles, nanotubes

Both biomimetic and bioinspired approaches lead to complexes that serve as the springboard for discovering more efficient reactions that are useful to chemists. Future challenges will have to incorporate the more structural elements found in both the primary and secondary sphere found in metal proteins. This includes using non-covalent interactions to influence chemical reactivity. These interactions are essential in modulating chemical reactions, especially for selective reactivity. Methods to accomplish this are still needed. One promising area is in the de novo


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design of metallpeptides. DeGrado and Dutton's work on electron transfer in de novo designed metallopeptides illustrates the utility of this approach. However, functional systems for chemical transformations are still lacking. Future efforts will be on developing methods to make new ligands, scaffolds or peptides that yield a diverse group of metal complexes. While rationally designed systems are still essential in future discovery of this type, combinatorial methods cannot be overlooked. Rapid methods for making and screening a large array of complexes are needed to advance this area. A second approach that will be important in the future is developing bioinspired complexes in confined spaces. The goals are similar to those above, i.e, to making synthetic systems that reproduce or enhance the chemistry found in nature. This area encompasses a wide variety of synthetic disciplines, but, in the near future, most likely will combine synthetic inorganic chemistry with material science. The merging of efforts in these areas (breaking down unnecessary barriers between disciplines) is necessary for a productive future. 4. Environmental bioinorganic chemistry

• Oceans • Extreme environments (vents) • Toxic metals (Se, As)

The involvement of bioinorganic complexes in complex environmental systems will be an important, and wide-open, area of future research. 5. Dynamics of metalloproteins

• Motions related to catalysis • Docking

While most current structural biology is based on ground-state structures, the dynamics of biological systems and relationship of motions to function remain a forefront area of research. III. FINDING THE RIGHT BALANCE A. What is the right balance between fundamental and directed research; multi-

investigator vs. single-investigator grants? 1) We are already inspired by fundamental problems in Biology and by societal needs in

medicine, energy, and the environment.

2) This approach has been successful, in that discoveries from fundamental research have already proven critical to other scientific disciplines and to technology breakthroughs.


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Examples: - • Zn and development • Sensors based on electron transfer

B. What is the proper balance between single- and multi-investigator approaches? This discipline of bioinorganic chemistry is already highly collaborative

• Predominant mechanism is through single-investigator projects with arranged collaborations

• Mechanism is already very successful The group favors primary funding for single-investigator driven research

Autonomy: • drives timely progress • allows for flexibility in collaborations required for fast response to new discoveries

Circumstances appropriate for formal multicollaborative grants include:

• Defined, established questions • Need for motivation and resources for highly integrated and synchronous research • Widely disparate fields and long-term questions

Example areas: -

• inorganic chemistry in neuroscience • biogeochemistry

C. Can the hot areas of the future (as identified above) be worked into existing NSF

initiatives?

Not really addressed; all members of group have single-investigator ‘basic research’ funding from NSF D. Can the identified hot areas be used to develop other initiatives across NSF (not just

within IBO and CHE, but across other divisions as well)? Potential example areas:

• inorganic chemistry in neuroscience • biogeochemistry

E. How can the inorganic community work together most effectively to take advantage of

existing initiatives and promote new ones?


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Not addressed

F. Balance' Summary The field of bioinorganic chemistry has thrived precisely because it is a highly interactive, collaborative group that is driven by research needs to constantly push for new techniques and partnerships. This success has been met, however, in the context of investigator-initiated and single-investigator grant programs that are based on problems in basic research. Single-investigator grants require, and therefore produce, high-impact results produced in a timely fashion. This structure also allows flexibility to collaborate as needed. Potential areas were identified in which structured collaborations could be beneficial. IV. FURTHER REMARKS: A. Opportunities for inter-group scientific interactions

• Biocatalysis related to design of new catalysts, industrial processes • Environmental chemistry:

o Bioremediation o Microbial-mineral interactions o Biogeochemistry o Toxic metals

New frontiers such as inorganic chemistry neuroscience and inorganic biogeochemistry have a strong chance of thriving if this field is ensured continued support for basic research. B. A New Theme/Title for the Area: Inorganic Chemistry of Life Examples for public dissemination

• Lance Armstrong and Pt compound • In vivo image and Gd/Tc compound • Crops and nitrogenase MoFe cofactor • Prions and Cu • Nerve cell and K+ channel (+ detail of K+ ligands) • Valdez bioremediation • Egg/Ca2+ image for biosensors • Toxic metals- paint and children • Antibiotics: Tb-KatG story • Fe, Klausner

C. Bioinorganic Chemistry and Education Bioinorganic chemistry is one of the most effective disciplines for training students in


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fundamental topics and the broader scope of science. Students in this area are trained as scientists experienced in the power of collaboration for achieving goals. Students with small-molecule modeling projects in particular receive desirable training in synthesis and evaluation, as well as education in biological systems. This field has a strong tradition of mentoring through the Graduate Student Gordon Research Conference and previously NSF-supported Summer Workshop in Bioinorganic Chemistry (Georgia). D. Existing and Emerging Techniques Critical For and Stimulated By the Field

• Higher sensitivity in diffraction- detectors, sources • High-resolution (sub-angstrom) protein crystallography • Cryocrystallography • Crystallography of trapped intermediates • NMR at high fields • ENDOR (and ESEEM) Spectroscopies • Low temperature trapping of chemical reaction intermediates (modeling chemistry,

Davydov/Hoffman cryoreduction of proteins) • VF/VT MCD • Mossbauer • Magnetism and theory • X-ray absorption spectroscopy • Rapid kinetics • Single-molecule folding and reactions • Mass spectroscopy • reaction products, models • posttranslational modification • protein-protein and protein-DNA interactions • folding and accessibility


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Chapter 6 – Detailed Report on Chemistry on New Length Scales Group Leader: Chad Mirkin Contributors: Malcolm Chisholm Kim Dunbar Richard Eisenberg Susan Kauzlarich Jeffrey Long Figure 6.1. Frontier Areas for New Length Scales I. THE PAST AND PRESENT One of the grand challenges for inorganic chemists in the next decade is the development of synthetic and physical deposition methods for controlling the structure, composition, and functionalization of inorganic materials on the scale of 1-100 nm length, where mesoscopic properties between the molecular and the bulk are often evident. These dimensions are too small to be accessed by many conventional physical deposition methods (e.g. photolithography) but too large for many currently available synthetic methods. Moreover, structures on this length scale provide characterization challenges different from small molecule and bulk material systems. However, structures with nanometer dimensions, as well as higher ordered architectures formed from them, exhibit a wide range of fascinating properties, including: quantum confinement; size-, composition-, and shape-dependent light scattering properties; the ability to catalyze many technologically important reactions; and unusual magnetic behavior that might be exploited in the fabrication of high density information storage systems. The study of these novel inorganic materials already has led to technologically important structures that can be used as probes in biodiagnostic applications, while offering much greater target sensitivities and selectivities than conventional molecule-based systems. They also are showing promise as potential replacements for the electronic components found in many photonic and nanoelectronic devices. Recent developments in synthetic methods, characterization tools, and physical deposition strategies significantly address some of the aforementioned limitations. These include: the development of synthetic methods for quantum dots; the advent of scanning probe, electron beam, and nanosphere lithographies; templated syntheses for nanorods; and improved solution chemical methods for synthesizing certain metallic and semiconductor nanoparticles. However, we have just begun to realize some of the extraordinary possibilities for this nascent field,. Below, we outline some of the challenges and possibilities for research at the 1-100 nm scale.


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II. THE FUTURE Figure 6.1 illustrates nine example areas where inorganic chemists can have an impact on materials involving this new length scale. A. Nanoparticles While colloid chemists have become very good at controlling the size and dispersity of certain select compositions (e.g. Au, CdS, CdSe), it is very difficult to control the size and narrow the dispersity of Ag, Pt, and Si nanoclusters. Moreover, little is known about controlling the structural properties of other binary compositions such as metal oxides, and virtually nothing is known about ternary compositions. As the study of Au particles and the II-VI quantum dots led to an understanding and applications of plasmons and quantum confinement, studies of more complex materials in nanoscale form will lead to new, and perhaps, unanticipated properties as well as an increased understanding of the relationship between composition, size, and function. Methods for controlling nanoparticle shape stand as a daunting challenge for the inorganic chemist. Such processes are important because a particle’s shape, as much as size, controls its physical properties. Complex mixtures of Pt cubes and tetrahedra can be prepared, but purification and isolation of one general shape has yet to be achieved. Similarly, Ag sols often consist of complex mixtures of spheres, polyhedra, and rods, but there are no suitable methods for isolating or separating polyhedra or rods from such sols. A recent result suggests that through synthetic methods and an increased understanding of nucleation and growth for these novel materials, it may be possible to generate distinct shapes in a preconceived manner, Figure 6.2. Utilizing a surfactant and photoinitiated process, one can selectively convert bulk quantities of spheres into nanosprisms in high yield. Such studies indicate that research in this area could pay big dividends in terms of fundamental insight and technological promise. Finally, an ultimate goal in all of this work is achieving molecular purity, especially for the larger nanocrystals. This will provide the ability to precisely correlate particle size, composition, and structure with physical and chemical properties. Above a certain size, this may not be possible because of the small energy differences associated with defects. Nevertheless, depending upon composition, this could be possible for clusters in the 1 to 10 nm range. Indeed, a major fundamental advance would be to identify the upper limit for molecular purity for a given composition.

Figure 6.2 One of the primary goals in the field of New Length Scales is to learn how to rationally control the size and shape of new particles that result from specific reaction conditions.

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B. Surface functionalization – controlling physical properties via surface ligation Surface modification chemistry is the materials chemists’ version of coordination chemistry and provides a route for tailoring the physical and chemical properties of a bulk material or a nanostructure, simply through choice of surface ligating moieties. Although small molecule coordination chemistry can be used as a guide to select potential ligands for modifying a particular surface, mesoscopic properties must be considered when a bulk material is miniaturized. Although there are now excellent and heavily used techniques for modifying gold (e.g. thiol adsorption) and certain oxide substrates (e.g. trichlorosilyl or trialkoxysilyl adsorption), ways are needed to increase the stability of such structures and to generalize the methodologies to other materials. Moreover, a fundamental understanding of the interactions between adsorbate and surface is required to reap the full potential this methodology offers. Indeed, it is astounding that after two decades of work in the area of alkanethiol monolayers on gold and thousands of papers on the subject, there is still a dispute over the fundamental interaction between the adsorbate and surface. New and more general methods coupled with a greater understanding of existing methods are needed for important classes of materials other than Au, including Ag, Pt, GaAs and the cuprate superconductors. Moreover, we are in need of a greater understanding of how such chemistry changes as these materials are miniaturized to the mesoscopic scale. Several questions need to be answered. Will the chemistry of a neutral bulk surface (e.g. gold) reflect that of a highly charged nm scale gold nanoparticle? If not, what are the differences? How can such differences be used in the development of new technology? A second issue that remains unaddressed is the development of surface coordination chemistry strategies for selectively functionalizing the faces of an anisotropic particle. In transition metal small molecule chemistry, one can take advantage of the preferred coordination geometries and the metals affinities for specific ligands to design a coordination sphere of interest. This is not yet possible for nanoparticles but would offer new opportunities for the construction of complex nanoparticle architectures that are designed by virtue of specifically placed linking ligands on the faces of a polyhedron. The problem lies in the observation that the chemistry of the different faces of a 1-component nanoscopic particle are quite similar and it is difficult to design ligands with the specificity to bind selectively to one face in the presence of the others. Here, biology may play a role by offering strategies, such as phage display, for screening and identifying libraries of natural structures or biological mimics that exhibit the desired selectivity. C. New methods of characterization When one works with structures that have dimensions on the 1-100 nm length scale, the traditional characterization methods used to define the structures and properties of small molecules are not always applicable. The characterization of nanostructures requires the development of new methods, especially those that can be used to study individual particles or small quantities of collections of particles. Scanning probe and electron microscopies are two of


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the most powerful classes of characterization tools for structures that fall within this length scale. However, most of these methods offer little chemical information, so there is a major need for methods that couple such tools with surface spectroscopies. For example, a scanning probe capable of interrogating the topology of a surface while providing a Raman or IR signal would be extremely beneficial, and if sensitive enough, could revolutionize the characterization of such structures, and surfaces in general. It is likely that Raman spectroscopy will provide the answer here, since one can in principle use tips modified with surface-enhancing materials such as Au and Ag to get enormous increases in signal via the well known “SERS-effect”. A second problem with regard to the characterization of such structures lies in the clash between scientific cultures. Chemists and material scientists often rely on different techniques for characterizing their materials. Each group has a different set of accepted standards for a given material type, and it is important that a consensus be reached on the bare minimum required for the characterization of a given structure in this interdisciplinary field. As it evolves, perhaps journals can take the lead in defining such standards. D. Structure-function correlations The use of coordination chemistry in the synthesis of nanoscale molecules represents an emerging area of research with enormous potential. In this approach, metal complexes with fixed coordination geometries and featuring one or more labile ligands are combined with bridging ligands to generate a range of soluble molecular constructs. In many cases, reversible bond formation enables the repair of defects, which ultimately leads to pure molecular compounds in high yields. Armed with an understanding of the coordination preferences of the metal ions and bridging ligands, it is possible to direct the formation of specific structures (particularly, polygons and polyhedra bearing well-defined internal cavities), thereby permitting the design of species with a variety of recognition properties. Nanoclusters possessing cavities of tunable dimensions, shape, chirality, and functionality (e.g., hydrophobicity, or metal or anion binding capability) could yield applications in sensing, catalysis, and separations. While significant progress is being made along these fronts, it is clear that much work is needed to advance beyond the ~2 nm range.

The study of the physical properties of nanoscopic materials and molecules exhibiting useful chemical, physical, electrical, or optical properties requires synergistic activity and feedback into the design characteristics. Besides Single Molecule Magnets, another quest in this area of research is to obtain materials that exhibit completely new physical properties or those in which one property is combined with another property. Examples of such systems could be materials showing bistability, tunable magnetic ordering temperatures, discrete molecules/nanocrystals showing magnetic/thermal/photochemical hysteresis (nanomagnets, spin-crossover compounds), and hybrid materials coupling magnetism with conductivity or even superconductivity, or with optical properties. Other interesting phenomena that can be studied are for example quantum tunneling and long-lived photo-optical excited states in solids in restricted magnetic dimensionalities. Other obvious properties that need to be explored and correlated with the length scale of the material are ferroelectric properties and catalytic activity. There is also a need to prepare the materials in such a way as to be able to use their properties in devices. This


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includes the fabrication of thin layers and organized films, and their encapsulation/intercalation into polymers and solids. Another critical aspect is to develop suitable theoretical models based on solid-state approaches as well as on molecular orbital approaches with the ultimate goal being to predict the nature of the magnetic, optical or electrical response in spatially confined materials. E. Patterning, organization, and manipulation of inorganic nanostructures There are two general classes of strategies for organizing nanostructures into functional materials, those that rely on physical methods and ones that utilize chemical processes. Physical deposition methods typically involve tools, such as scanning probe-lithographies, e-beam lithography, and electrochemical or electrophoretic techniques, to either physically guide the placement of particles within an extended structure or to create physical or chemical templates that drive the assembly process. In the case of the lithographic methods, templates, made of solid-state inorganic or soft organic materials, are usually used to guide the assembly of nanostructures into higher ordered architectures based upon physical or chemical interactions with the preformed templates, Figure 6.3. These processes therefore can either rely on simple particle sedimentation and recognition of the physical features of the template or be quite complex and rely on recognition events between the particle building blocks and chemical components of the predefined templates. The other general approach to nanostructure assembly involves the use of chemical or biochemical recognition events between particle building blocks to guide the formation of preconceived architectures, Figure 6.4. The reason many researchers are turning to biological molecules such as oligonucleotides and proteins as the chemical linkers in such processes are the exquisitely tailorable recognition properties offered through the use of such molecules. Moreover, these molecules are often larger than the molecules available through conventional organic syntheses so they offer routes to materials with architectural dimensions not possible through small organic molecules. These strategies already have led to materials that are providing insight into what controls the optical and electrical properties of structures comprised of inorganic particle building blocks connected by these novel linker moieties. Moreover, they

Figure 6.3 Chemical templates, such as DNA, can be used to pattern and direct the assembly of inorganic structures on a surface.


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are being applied in the development of DNA and protein diagnostics. However, we are just beginning to learn what these materials can do from the standpoint of catalysis, light harvesting, nanoelectronics, and optics. These are fertile areas waiting to be explored by groups with the proper interdisciplinary background necessary to build and characterize structures from this new field of hybrid bioinorganic materials chemistry. F. Innovative uses for nanoparticle structures. Like catalysis, this is an area of inorganic chemistry where applications are not contrived but rather are making an important impact in a variety of tecnological arenas. For example, nanoparticle materials are being used for developing colorimetric assays that are exhibiting substantially higher selectivities and sensitivities than conventional molecular fluorophore-based assays. Quantum dots, which do not experience the photobleaching problems that molecular flourophores do, are being used as fluorescent labels in many protein screening applications. The quantum dots also have the unusual property that they all can be excited with the same source but emit at wavelenths that correlate with size. Gold and silver particles, which exhibit tailorable plasmon properties, are being used as Raman enhancers in a variety of diagnostic applications. Nanorods made of different tailorable compositions are being used as nanobarcodes in a variety of powerful molecular diagnostic schemes. Nanorods having well-defined crystal faces at both ends can be used as laser cavities, leading to “nanolasers”, for which applications have only just begun to be explored. In addition, there is a widespread effort to develop means of synthesizing and manipulating conducting nanowires for use as interconnects in transistors. G. Coordination chemistry approach to nanoparticle synthesis – nanomolecules. The use of coordination chemistry in the synthesis of nanoscale molecules represents an emerging area of research with enormous potential. In this approach, metal complexes with fixed coordination geometries and featuring one or more labile ligands are combined with bridging ligands to generate a range of soluble molecular constructs. In many cases, reversible bond formation enables the repair of defects, leading to pure molecular compounds obtained in high yield. With an understanding of the coordination preferences of the metal ions and bridging ligands utilized, it is possible to direct the formation of specific structures (particularly, polygons and polyhedra bearing well-defined internal cavities), thereby permitting the design of species with a variety of recognition properties. Nanoclusters possessing cavities of tunable dimensions, shape, chirality, and functionality (e.g., hydrophobicity, or metal or anion binding capability) could yield applications in sensing, catalysis, and separations. While significant progress is

Figure 6.4. DNA-driven assembly of nanoscale bioinorganic composite materials.


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being made along these fronts, it is clear that much work is needed to advance beyond the ~2 nm range.

Recently, researchers have developed some impressive methods for constructing “zero”-, one-dimensional, two- and three-dimensional supramolecular structures through relatively simple concepts in coordination chemistry. A number of synthetic strategies have been developed, but most fall into the category of Directional Bonding. One emerging strategy is based on the realization that supramolecular interactions often play a decisive role in stabilizing a particular structure. One that has emerged as a powerful tool is the use of an anion to control the size and shape of a self-assembled cyclic oligomer as shown in Figure 6.5.

These synthetic approaches allow one to build multimetallic structures in high yield with excellent control over architectural parameters and properties (shape, size, hydrophobicity, redox-activity, optical activity, and chirality). We are just beginning to learn what one can do with these materials from a functional standpoint. Shape control makes them particularly attractive for applications in the areas of catalysis, sensor receptors, and molecular mixture separations. Recent work has raised the intriguing possibility of using nanoscale molecular clusters such as those depicted in Figure 6.6. as data storage media. These molecules have been shown to exhibit magnetic bistability at very low temperatures, by virtue of possessing a ground state with a combination of high spin, S, and a large negative magnetic anisotropy, D. To raise the blocking temperature in these “single-molecule magnets”, it is necessary that chemists devise methods for synthesizing new nanoscale clusters that involve control over these critical parameters. Ultimately, such compounds could lead to new technology for storing data at vastly increased surface densities, giving rise to a new generation of fast and efficient computers.

[Ni5(bptz)5(CH3CN)10][SbF6]10•2CH3CNFigure 5.

Figure 6.5 Choice of anion is critical to formation of the cyclic oligomer [Ni5(bptz)5(CH3CN)10][(SbF6)10]•2CH3CN.


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H. Nanotubes and nanowires Carbon nanotubes as well as transition metal versions should be considered inorganic nanostructures. Many questions have yet to be answered regarding the preparation and properties of carbon nanotubes such as:

• Can methods be developed for controlling structure? • Structure function relationships. • Mechanistic insight – how do we get it? • Use of nanoparticles/nanowires in developing “molecular electronics” • What are the intrinisic electrical properties of molecule – structure versus function. • Can we find good molecular analogues to solid-state materials? • Addressability – How do we address nanoscopic structures in mass • Can innovative structures be fabricated that demonstrate unique capabailities?

Figure 6.7.

Figure 6.5 Nanoscale clusters with novel magnetic properties hold promise for applications such as data storage.


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Chapter 7 – Detailed Report on Environmental Inorganic Chemistry Group Leader: Mary Neu Participants Kristin Bowman-James Bruce Bursten Jonathan Sessler Tom Spiro Mahdi Abu-Omar, Gui Bazan, and James Espenson also participated in some sessions. I. INTRODUCTION

To meet society’s needs and the challenges of planetary stewardship, inorganic chemistry research must develop methodologies and tools to: minimize negative environmental impacts, reclaim and wisely use finite resources, and better understand inorganic chemistry in nature. Consequently, research topics are divided into the following three subtopics: • Pollution Prevention and Resource Conservation (‘Green Chemistry’). Opportunities to

reduce the environmental impact of chemical processes and to minimize the use of energy, water, and other resources will depend on advances in catalysis, biocatalysis/bio-transformations, pollution-free transformations, solvent free chemistry, non-fossil fuel based products, microscale chemistry, fuel cells, and battery technology.

• Inorganic Chemistry in Nature. Inorganic chemistry permeates Nature with abundant examples in atmospheric science, geochemistry, and biogeochemistry. These include the natural and industrial cycling of metals, anions, carbon, nitrogen, and sulfur, and manipulation of other inorganic species including metal ions. Opportunities for advances encompass nitrogen fixation, photosynthesis, water/solid and organic/inorganic interfaces, the theory and modeling of transport, natural systems integration, and fabrication of biomimetic systems.

• Inorganic Chemistry of Hazardous Species. Inorganic chemistry is fundamental to understanding the behavior of both naturally-occurring and anthropogenic hazardous species. Research advances are needed in understanding the environmental distribution and speciation of contaminants, their toxicity and environmental impact, and ultimately their treatment and remediation.


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A recurring theme in discussions was that research advances in nearly all the subfields of inorganic chemistry are relevant to the environmental arena. Some specific research topics in common with other areas of endeavor in inorganic chemistry are:

o small molecule transformations, o bioinorganic chemistry, o catalytic/organometallic chemistry, o biological and geochemical metal transformations, o metalloproteins, o carbon cycling, o theoretical chemistry, including advanced computing and modeling, o molecular recognition, o sensing, o interfacial phenomena, and o chemistry in confined spaces.

II. PAST AND PRESENT ACCOMPLISHMENTS A. Pollution prevention and resource conservation. Waste reduction and decreased environmental impact have been accomplished by applying the fruits of research in inorganic chemistry to industrial processes and consumer products. For example, chemical transformations using traditional inorganic oxidants (such as peroxide) can be accomplished in new ways, exemplified in the ‘green’ catalysts developed by Craig Hill and Terry Collins that are now used in the paper industry in place of vast quantities of hazardous solutions (Figure 7.1).ix,x

Inorganic chemists have redesigned processes to minimize waste by making syntheses, separations and purifications more efficient, and by utilizing non-traditional benign solvents. An example of ‘supercritical’ success is the reaction rate of hydrogenation of alkenes catalyzed by water-soluble rhodium-phosphine centers, which is significantly improved in water/supercritical carbon dioxide. After reaction, the emulsion can be broken by decreasing the pressure to isolate the product and to recover the catalyst (Figure 7.2).3 As evidence of the potential impact of these systems, DuPont’s Teflon production plant now utilizes CO2 where organic solvents were conventionally used.

Figure 7.1 Collin’s tetraamido macrocyclic ligand is used to oxidize aqueous contaminants in efflux from the paper industry.1,2


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Figure 7.2 A water/supercritical carbon dioxide emulsion containing 1 wt% nonionic poly(butylene oxide)-β-poly(ethylene oxide) surfactant (40 ºC, 4000 psi) (left) shown at the left. After decreasing the pressure to 2000 psi a biphasic water-CO2 system is formed, right.

Natural cycles of inorganic species are significant in our lives, with both positive and negative effects. For example, tremendous advances in manipulating ozone chemistry now allow ozone to replace chlorine in water purification and ozone-removing catalysts (critical to the aerospace industry) have been developed. Strides have also been made in understanding the fundamental inorganic chemistry governing ozone depletion in our atmosphere. B. Inorganic Chemistry in Nature. Nature provides its ultimate catalysts, enzymes, which readily perform incredible feats of chemical transformation. Evolution has also carefully crafted chemical systems that sequester species for transport and integrate them to detoxify contaminants. Nonetheless, there have also been human successes in utilizing natural products and enzymes in the bioremediation of contaminated land. Prefabricated enzymes found in some plants that can accumulate large quantities of toxic metal ions can be used for remediation efforts. For example, the enzyme mercury reductase, which reduces mercury ions, has been successfully inserted into a water-weed as part of a ‘green metal smelting process,’ that removes mercury from contaminated water.4 Successes such as these rely on a basic understanding of the concepts of inorganic chemistry in Nature. Biomimetic analogs of metalloenzymes and metalloproteins also hold promise for future advances in remediation. Metal ion chelators, as exemplified by Raymond’s model siderophore systems5 could sequester and remove undesirable metal ions from the environment. C. Inorganic Chemistry of Contaminants. An impressive example of the use of inorganic chemistry in remediation efforts is an in situ inorganic redox manipulation, based on the reduction of Fe(III) by dithionite, that has been developed and deployed at the Hanford Site in eastern Washington. In a permeable treatment zone, carcinogenic and highly mobile Cr(VI) is reduced to the less mobile Cr(III) by surface-bound and structural Fe(II) species formed in aquifer sediments by injected reagents. Building on this approach, it may be possible to stabilize contaminants, such as trichloroethane and


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pertechnetate,6 in reduced forms that are less toxic and mobile A promising effort in the pilot plant stage uses molecular recognition to remove highly radioactive Cs-155 from the Savannah River site. In this approach, Bruce Moyer’s group at Oak Ridge National Laboratory combines the selective sequestration of cesium by a calixarene/crown combined receptor with an added component to assist counterion extraction.7 In this and other efforts toward environmental decontamination, cost efficiency is a key issue that places even higher demands on design concepts. As can be seen from these few examples, the three areas of inorganic environmental chemistry blend at the interfaces. While no one can accurately predict the benefits of fundamental research, we are clearly on the verge of great changes in environmental science where inorganic chemistry can have immense impact. Other exciting and expanding fields of high technology also offer tremendous promise, including new brilliant and tunable synchrotron light sources that can probe ultra-trace samples, as well as amazing advances in microscopy and imaging. III. OPPORTUNITIES FOR ENVIRONMENTAL INORGANIC CHEMISTRY A. Pollution prevention and resource conservation (Green Chemistry). Key initiatives should involve:

• revolutionizing industrial processes so that, by design, they feature atom economy and environmentally benign reagents;

• identifying alternative ‘green’ reaction media, such as supercritical fluids, fluorous phases, ionic liquids, water, and even solventless reactions;

• decreasing waste in separations; and • providing and improving new types of energy sources, such fuel cells and batteries.

Industry can benefit greatly from economical and environmentally benign methodologies. New catalysts that employ and activate air, nitrogen, water, ammonia, and carbon dioxide, and ideally operate under ambient conditions to minimize energy costs, are natural targets. Especially important are selective oxidations with air and other ‘green’ oxidants such as hydrogen peroxide. Targeted in these efforts are transformations of cheap and readily available compounds, such as alkenes and alkynes, to valuable synthons for commodity chemicals and pharmaceuticals. Even more dramatic research advances, potentially yielding huge benefits, involve C1 chemistry. These efforts are exemplified by direct methane oxidation, gas to liquid transformations, and efficient carbon–carbon bond formation. Asymmetric catalysis is also ripe for future exploration and development, since the demand for enantiopure drugs continues to increase. Other key targets for Green Chemistry are alternative ‘solvents.’ As an example, room temperature ionic liquids are low melting organic salts generally composed of unsymmetrical organic cations and weakly coordinating anions (e.g., BF4¯, PF6¯, and N(SO2CF3)2¯ salts of the cations shown below).8, 9 Although still regarded as exotic, ionic liquids are perceived as ‘green’ solvents based on their non-volatility and significantly reduced flammability hazard. Their use


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in homogeneous catalysis has been stimulated by their ability to solvate and stabilize highly charged metal species while simultaneously maintaining non-polar organic materials in solution. The distinctive ionic character of these solvents also provides electrical conductivity that can be exploited in electrochemical applications, such as the design of novel metal purification and separations schemes. Examples of these ionic liquids are shown below:

As noted above, supercritical fluids are another successful class of alternative solvents that will continue to develop. Water/supercritical carbon dioxide emulsions are now being used for biphasic homogeneous catalysis, leading to higher reactivities and more facile separations compared to conventional biphasic catalytic systems.

While substantial waste reduction in separations has been realized through engineering advances by optimizing the number of theoretical plates, miniaturizing components, downscaling, etc., further progress is possible through environmental inorganic chemistry. Hybrid or composite materials for separations could be designed to retain the desirable characteristics of current substrates, such as size selectivity, but with added chemical features, such as product polarity or hydrogen-bonding properties. Organic polymers on alumina, inorganic/biological materials, as well as multifunctional-layered (inorganic substrate/gold layer/organic monolayer) materials, all have the potential to be highly energy efficient and selective.

Fuel cells could reduce our dependence on fossil fuels for transportation, but require research to overcome the technological barriers that preclude their widespread use. Examples of inorganic research goals are to:

• develop solid state materials that store hydrogen as densely as hydrocarbons; • devise a means of producing hydrogen without CO2 as a byproduct; • find a way to decompose water to produce hydrogen in an energy efficient process; and • utilize methane as a fuel.

While fossil fuels continue to be sources for much of our energy, we must minimize byproducts detect and abate NOx and SOx, and sequester CO2. Likewise, fundamental research on the mechanisms of charge transport in new battery materials with partially ordered structures could lead to the design of even better materials. There is evidence that structural domains below the diffraction level are key to conductivity, yet structure/function relationships have not been explored. Advances in this area could lead to better energy efficiency and improved energy storage.

N NN++ + +N+

O

O N+ N + N

O

N

EMI BMO BMP MOMP BMPP BMM


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B. Inorganic chemistry in nature. Biocatalysis and speciation comprise the two main categories in this subtopic. Key initiatives for both involve:

• acquiring a better understanding of the • chemistry involved, and • providing chemical models.

Global element cycling is controlled by the microbial world, and inorganic chemistry is at the heart of biological transformations. However, human activities have strong impact on global element cycles. Prominent among these are:

• carbon cycling through photosynthesis/respiration, being influenced by increased atmospheric CO2 levels from fossil fuel combustion;

• nitrogen cycling through N2 fixation/denitrification, being influenced by increased nitrogen circulation from fertilizer production (accounting for half of the world’s fixed nitrogen); and

• metal redox cycles through aerobic/anaerobic microbial metabolisms, being influenced by issues such as global mercury loading from mining and manufacturing.

All of these processes are catalyzed by metalloenzymes (cytochrome oxidase, manganese water oxidase, nitrogenase, sulfite reductase, etc.). For many elements multiple potential pathways between biotic and abiotic systems are known to be important; however, the transfer between these systems is generally not known. Understanding the mechanisms of these metalloenzymes and their linkage reactions is fundamental to understanding the elemental cycles, and key to future remediation efforts, in terms of both utilizing the natural enzymes as well as providing key input to biomimetic systems. Biocatalysis, essentially aqueous chemistry in Nature in which catalytic reactions play a role, can provide valuable insight and is worthy of imitation. Potentially most important and attainable are duplications of net stoichiometry of molecular rearrangements and transformations of various types accomplished in water. Research could spring from that base by then demanding more of the mimic: for selecting one substrate from several, in specificity for a single target, for transforming one enantiomer and not the other. Catalysts of this type cannot be purchased.


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Structural and mechanistic enzyme studies will be a major basis for advancement. Natural systems have evolved geometric (clefts, channels, proximal/distal ligation, etc.) and chemical (H-bonding, superstructures) features that are built into active sites. With that realization, biocatalysis will certainly have ligand design as one focus (an area that can benefit from multi-investigator efforts with organic chemists). By and large, however, the ancillary ligands (following Nature’s lead) should be ones inherently adapted for aqueous solution. For example polypeptides histidines, cysteines, etc., may be superior.

Thus, advances in biocatalysis and bioinorganic models could proceed stepwise as follows:

• gaining knowledge on how natural biocatalysts function in terms of mechanism and structure;

• designing and preparing synthetic compounds that first reproduce stoichiometry and, to a growing extent, provide specificity;

• evaluating mechanisms, carefully and quantitatively, to gain the level of understanding through which improved designs can be realized; and

• obtaining a growing sophistication in ligands/receptors and catalytic design, to gain ever greater control.

Speciation, the availability and delivery of the required metals to microorganisms,are key to alterations in element cycling. For example, there is strong evidence that very low solubility of iron in the open oceans limits biological productivity and the carbon cycle.However, the discovery of a new class of siderophores in marine bacteria by Alison Butler’s group could help unravel some of the mystery concerning these issues:10

Another striking example of metal control of the marine carbon cycle is the recent discovery that cadmium can substitute for zinc through the expression of a novel cadmium carbonic anhydrase in algae.11 Many other aspects of element transport and cycling involve redox, complexation, and precipitation/dissolution steps, that (perhaps surprisingly) still need to be characterized and quantified.

Understanding the environmental behavior of an element generally begins by learning its fundamental aqueous chemistry and natural distribution. Sequential progressions include the elucidation of:

• its atmospheric and terrestrial geochemistry; • its bioinorganic and biogeochemistry; and • the reactions and relationships between phases of its environmental cycle (mineralogy,

O

N OH

HO

O

HN

O

HO

NH

O

N OH

O

HN

O

HO

NH

O

O

OHN H

N

NH

OHO


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aqueous chemistry, etc.). For most elements a great deal is known in one or more of these aspects of their global cycles, but all-important details, whole areas, or the transformations between parts of their cycle remain mysterious. Two examples serve as illustrations, mercury and iron. Mercury is transported atmospherically as Hgo, but its reactions and biological uptake involve Hg2+, but the mechanism of Hgo oxidation is not really understood. Likewise, iron is arguably the most well-understood major environmental metal because of extensive study of its fundamental properties, mineralogy, geochemistry, and bioinorganic chemistry. Despite this, we do not fully understand how it is transferred from abiotic to biological systems, although significant strides have been made in this area through model chemistry (Figure 7.3). Although models have provided some insight, we have yet to make structural/functional analogs of specific iron metalloproteins that can truly mimic the performance of the natural proteins. Nor can we predict the consequences of increasing the concentrations of iron in coastal waters (intended to spur carbon sequestration). Figure 7.3 Proposed siderophore shuttle iron uptake mechanism: The normal state (A) has iron-free siderophore in


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the outer chamber, followed by (B) iron exchange, (C) conformation change, and (D) release of the siderophore. 12

Understanding all of these component reactions, cycles, and the human impact on them poses major challenges to inorganic chemists. At least we would like to understand them sufficiently well to be able to reproduce desirable transformations and avoid deleterious ones. And perhaps at best we will understand the inorganic chemistry of our world. D. The environmental inorganic chemistry of contaminants. Key initiatives are to:

• gain a better understanding of the fundamental inorganic chemistry and environmental behavior of contaminants;

• improve assessment of toxicology; • develop and implement new remediation techniques; • develop better in situ stabilization and monitoring methods; and • develop more highly selective receptors and sensors.

Understanding the chemistry and environmental behavior of contaminants is the key to a better evaluation of risks and remediation strategies. Species of interest include RCRA (Resource Conservation & Recovery Act) and other ‘listed’ metals, anions, and even organics, as the fate of the latter is influenced by interactions with inorganics. For some contaminants, even their hydrolysis reactions have not yet been quantified, and for others their affects on human and environmental health are not known. From this perspective, speciation, inorganic transformations, biogeochemistry, and environmental transport are areas that should continue to be researched. Interfacial reactions are increasingly thought to govern the overall fate of contaminants. Therefore, it is essential to understand the chemistry of sorption/desorption, multilayer formation and characteristics (e.g., sediment/biofilm/contaminant), and surface catalyzed degradation. Science needs in this area therefore include:

• fundamental thermodynamic and kinetic studies on species; • studies of reactions at interfaces; • fabrication of sensors (molecular recognition, signal generation, and signal transduction);

and • elucidation of the mechanisms of natural and accelerated degradation, including biotic

and abiotic transformations, human and environmental health effects, and remediation.

For decades the general goal of environmental restoration has been to remove contaminants either to a regulatory level or to the analytical detection limit, and to do it as soon as possible. For some pollutants, regulatory values, such as drinking water standards, decreased as analytical methods improved, but not necessarily as more precise and sophisticated toxicological studies and risk analyses were conducted. And for some metals the allowable groundwater levels set in one state have been adopted in other states where the metal is naturally present at levels higher than the standard (due to different underlying geology). These and similar issues, which can have significant environmental ramifications, such as incorrect prioritization of clean-up needs


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and resources, and ballooning remediation costs, are only beginning to be addressed. Advances in research areas such as

• contaminant transport pathways and velocities, • in situ characterization, and • threshold dose/health response determinations,

to name but a few, could be of tremendous value in enabling science-based environmental stewardship. Consider, for example, a situation where inorganic chemistry research shows that a particular metal at a mixed-contaminant site is present in a less toxic form than previously thought. Furthermore, it is approaching an underlying aquifer orders of magnitude more slowly than oxoanions or organics also present. The site stakeholders and regulators could decide to bioremediate the organics and anions in situ. The migration and speciation of the metal could then be monitored, rather than use the conventional, more disruptive, and costly approach of ‘muck and truck’. Developing and implementing new remediation techniques require fundamental and applied research. While microbial degradation of organics is currently the preferred option for a wide range of sites, bioremediation of most metals and other inorganics is still in its infancy. Similarly, there has been great success in phytoremediating lead, but less for other inorganic targets. These areas could gain from inorganic and multi-disciplinary research on molecular recognition, uptake and metabolic processes for inorganics in plants and microorganisms, genetic engineering, and plant/bacteria symbiosis. The use of biologically-based or multi-layer barriers has great promise, but their design and use require a wide range of research. There is economic, political, and technical impetus to rely more heavily on natural attenuation, containment, and in situ stabilization of contaminants. These approaches demand accurate and defensible answers to persistent questions regarding contaminant toxicity and environmental mobility:

• What form and concentrations of contaminants induce health effects? • How mobile and bioavailable are particular forms of contaminants and their ‘carriers’

(anions, cations, natural organic matter, microorganisms, etc.)? • How does that depend on site specifics, such as underlying geology, hydrology, climate,

contaminant mixtures, site/local land and water use? • What are the mechanisms of natural attenuation, and how can we accelerate their rates? • Can barriers be reactivated in situ?

In turn, these questions each have numerous fundamental research needs. Sensing, particularly remote sensing, must be more rapid, specific, and accurate. Geochemical flow and transport modeling must be able to accurately predict migration rates. This requires considerably more experimental data than are available for most contaminants, and more sophisticated theory and computational methods. In all phases of environmental restoration there is immediate need for molecular receptors in the form of selective sensors, capable of multi-analyte detection, as well as extractants and sequestering agents. Given this, key challenges for the future involve understanding the basic


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determinants of substrate-receptor interactions and using the resulting fundamental knowledge to prepare species that can bind, sense, carry, or transport target species over a range of concentrations and under a variety of conditions. Included in these efforts are anions as well as cations.

Often overlooked, anions are also critical inorganic environmental species, and the removal of selected anions is required to effect the in-site stabilization of waste sites and their remediation. Currently, the chemistry of anion recognition remains in its infancy, since simple inorganic anions have been exceedingly difficult to target for selective recognition.13 Thus, this environmentally important area can be viewed as one with both tremendous societal import and one where a considerable predictive basis of fundamental science remains to be developed. It has only been in the last two decades that significant advances have been made in receptors for specific anions, such as the nitrate host shown, which binds two nitrates within a single receptor cavity.14 In addition to halides and oxoanions of traditional environmental importance, anthropogenic anions with more complex geometries, such as glyphosate (Roundup®), are also of concern. The diversity of shapes and low charge densities make the recognition of anions a challenge, especially in aqueous environments. Given this, a key goal for the future involves acquiring a better understanding of the basic determinants of anion-receptor interactions.

The inorganic community is poised to address critical needs in water quality control and remediation as well as in situ stabilization and monitoring throughout the environment. By virtue of their long-term expertise and knowledge for understanding and manipulating of inorganic species, including basic coordination, main group, and organometallic chemistry, inorganic chemists can provide key roles in environmental stewardship. E. The role of theory in environmental inorganic chemistry.

Although not listed as one of the three areas of environmental inorganic chemistry, the role of theory is increasingly important in the design of chemical receptors and understanding of mechanistic pathways. Key issues to be addressed are:

• the prediction of thermochemical properties of complex metal-containing molecules and of their reactions to allow for prescreening of catalysts;

• accurate modeling of microscopic and macroscopic phenomena, including the behavior of molecules under “real” conditions, such as in solution or within a solid support;

• the merging of accurate quantum chemical approaches with methods for the accurate prediction of transport properties to enable modeling of geochemical and biogeochemical phenomena; and

• the development of new methods of informatics for mining existing data on


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environmentally relevant inorganic molecules.

Quantum chemical and computational modeling methodologies are already available to address some of the broad questions. For example, recent advances in relativistic quantum chemical methods, such as relativistic density functional theory, have enabled the accurate prediction of structures, spectroscopic properties, and relative energetics of many actinide-containing systems, including some of those relevant to nuclear waste remediation. Addressing future questions will require an even greater breadth of theoretical formalisms, relying on a continual increase in computing and supercomputing capabilities. Challenges in the field of environmental inorganic chemistry can provide the stimulus for the development, application, and benchmarking of new quantum chemical, molecular modeling, and statistical mechanical formalisms. Thus, the challenges of answering some of the exciting future questions in environmental inorganic chemistry (and in broader future areas of inorganic chemistry as well) will require the close collaboration of experimental and computational chemists.

IV. CONCLUSION.

Environmental issues are of overwhelming societal importance and environmental inorganic chemistry clearly bridges many topics, both inside and outside of the inorganic realm. Consequently, advances in the area can only benefit from interdisciplinary research. Inorganic chemists can and will provide significant contributions over the next decades that will benefit the earth and its multitude of inhabitants.

References for Chapter 7 (1) Hill, C. L. Nature 1999, 401, 436-437. (2) Collins, T. J. Pure & Appl Chem. 2001, 73, 113-118. (3) Jacobson G. B.;Lee, C.T.; Johnston, K. P.; Tumas, W. J. Am. Chem. Soc. 1999, 121,

11902-11903. (4) Jones, D. Nature 2000, 406, 34. (5) Raymond, K. N. Coord. Chem. Rev. 1990, 105, 135-153. (6) Fruchter, J. S.; Cole, C.R.; Williams, M.D.; Vermeul, V. R.; Amonette, J.E.; Szecsody,

J.E.; Istok, J. D.; Humphrey, M. D. Ground Water Monitoring and Remediation 2000, 20, 66-77.

(7) Bonnesen, P. V.; Delman, L. H.; Moyer, B. A.; Leonard, R. A. Solv. Extr. Ion Exch. 2000, 18, 1079-1107.

(8) Bonhôte, P.; Dias, A. P.; Papageorgiou, N.; Kalyanasundaram, K.; Grätzel, M. Inorg. Chem. 1996, 35, 1168-1178.

(9) MacFarlane, D. R.; Meakin, P.; Sun, J.; Amini, N.; Forsyth, M. J. Phys. Chem. B. 1999, 103, 4164-4170.

(10) Martinez, J. S.; Butler, A. Science 2000, 287, 1245-1247. (11) Lane, T. W.; Morel, F. M. M. Proc. Natl. Acad. Sci. U. S. A. 2000, 97, 4627-4631. (12) Figure provided courtesy of K. N. Raymond.


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(13) Supramolecular Chemistry of Anions, Bianchi, A.; Bowman-James, K.; García-España, E., Eds. Wiley-VCH: New York, 1997, 461 pp.

(14) Mason, S.; Clifford, T.; Seib, L.; Kuczera, K.; Bowman-James, K. J. Am. Chem. Soc. 1998, 120, 8899-8900.


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Chapter 8 – Possible Educational Uses for This Report While not a central focus of this Workshop, education is a primary mission in Inorganic Chemistry, as it is in other areas of Chemistry. A recurring theme of the Workshop was the excellent education acquired through a doctoral program in Inorganic Chemistry. The typical student acquires a firm grounding in synthetic techniques, spectroscopic methods of characterization, and the application of theory to experiment. This foundation is then applied to a problem which inevitably spans multiple disciplines. Thus, for example, in Bioinorganic Chemistry the student acquires insights into the biology as well as the chemistry of his/her problem; in Environmental Chemistry, the student acquires insights into other areas (e.g., geology), as well as chemistry, and so on in every Thematic Area. In short, an education in Inorganic Chemistry produces a well-trained individual who can solve new problems and meet new challenges as they arise.


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Appendix I. Detailed Schedule Of Workshop Saturday, September 8, 2001 2:00 Registration 2:30 Introductory Remarks (Kristin Bowman James)

• Why are we here? • Who are we? (explain idea of breaking into focus groups, rationale behind

choice of groups) • What are we trying to accomplish? • Introduce Mike Clarke

3:00 Statement from NSF Staff (Mike Clarke) 3:15 Introduction to the Opening Lecture (Brian Hoffman)

• Where have we come? • Explain why Steve was chosen to speak

3:30 Opening Lecture (Stephen Lippard) 4:15 Organizational Remarks (Kristin Bowman-James)

• Cash Bar & Dinner – Location • Signing up for Groups (people should sign up for any group that they

think that they are likely to participate in) at Cocktail Hour • Introduce John Magyar • Other Announcements

4:30 Organizational Meeting with Group Leaders (KBJ and BMH)

• How to run a tight ship in the breakout groups • Our expectations: outline of points raised at the end of each breakout

session; presentation (overheads or powerpoint) at panel discussion • Pointers on how to get everyone involved and keep discussion going.

5:00 Cocktails/ Sign up for Focus Groups

• Six poster boards with name of group & summary of what each group entails on wall; group leaders should hang out near posters to answer participant questions

6:00 Banquet


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8:00 Mixer Sunday, September 9, 2001 7:45 Continental Breakfast 8:30 Breakout Group: Inorganic Chemistry for the Coming Decade

Topic: Identify important accomplishments, current hot areas and future priorities for the subdiscipline of inorganic chemistry represented by that group (new fundamentals, new length scales, catalysis, bioinorganic, materials, or environmental chemistry). The most time/emphasis should be placed in discussion of priorities for the future (should spend no more than half an hour on the past & present) Report should include:

• Important accomplishments of this subdiscipline in the past (listed as bullets; provide references if possible)

• Current “hot” topics in this subdiscipline (listed as bullets) • Future: what are the important questions/issues waiting to be addressed?

(listed as bullets) • Summary (one paragraph)

10:00 Organize & Prioritize Results of Group Discussions/ Draft Presentation for Panel

Discussion 10:30 Coffee Break (located at central meeting room) 10:45 Panel Discussion: Inorganic Chemistry for the Coming Decade (Moderator: Dick

Holm) • 10 minutes per group to present what they feel are the most important

questions/issues waiting to be addressed in their subdiscipline • 5 minutes per group (or 30 minutes total at the end) of response/discussion

as an entire workshop (12:15 Lunch should be set up by CM staff) 12:30 Lunch (during lunch: John collects computer files and overheads from group leaders for first breakout session; KBJ and BMH review these to make sure that they are getting the appropriate information; give feedback to group leaders on what they should be doing if necessary)


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2:00 Breakout Group: Finding the Right Balance

Topic: What is the right balance between fundamental and directed research; multi-investigator vs. single-investigator grants? Report should include:

• Go back through “future” bullets identified in morning breakout session; which one are “fundamental” scientific advances and which are “directed science”?

• Go back through “future” bullets identified in morning breakout session; which one are best addressed by a single investigator? Which will most likely require a multi-investigator approach?

• Summary (one paragraph)

3:00 Organize & Prioritize Results of Group Discussions/ Draft Presentation for Panel Discussion

3:30 Coffee Break (located at central meeting room) 3:45 Panel Discussion: Finding the Right Balance (Moderator: Chuck Casey)

• 10 minutes per group to present what they feel are the most important questions/issues waiting to be addressed in their subdiscipline

• 15 minutes for response/discussion as an entire workshop 5:15 Evening free for informal get-togethers and discussions (before leaving: group leaders give computer notes and overheads from second breakout group to John) Monday, September 10, 2001 7:45 Continental Breakfast 8:30 Breakout Groups: Iteration and Integration

Topic: Based on what you have heard from the other groups and discussed yesterday, are there any new opportunities or frontiers that are relevant to your group that weren’t on your original list? Are there ways that your group could help other groups scientifically or interface with other groups? Were these six groups a mistake? (Are there other groups that better represent the field and the future that should be added?)


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Report should include: • Future: a more complete list of the important questions/issues waiting to

be addressed (listed as bullets) • Opportunities for inter-group scientific interactions • Other new groups that you would add • Summary (one paragraph)

10:00 Coffee Break (located at central meeting room) 10:15 Final Panel Discussion (Moderator: Rich Eisenberg)

• 5 minutes per group to present what they feel are the most important questions/issues waiting to be addressed in their subdiscipline

• 15 minutes for response/discussion as an entire workshop 11:00 Closing Remarks (Richard Eisenberg ) 11:25 Thanks and Farewell (BMH & KBJ) 11:30 Lunch (during lunch: John collects computer files and overheads from group leaders) 1:00 Meeting of Organizers and Group Leaders; Regular Participants depart for

Denver International Airport 3:00 Group leaders depart for Denver International Airport


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Appendix II. List Of Workshop Participants Name Institution Role

Abu-Ohmar, Mahdi University of California, Los Angeles

Participant

Bazan, Gui University of California, Santa Barbara

Participant

Borovik, Andrew University of Kansas Participant Bowman-James, Kristin

University of Kansas Co-PI

Bursten, Bruce Ohio State University Participant Burland, Donald M. Acting Director, National Science

Foundation NSF representative

Casey, Charles University of Wisconsin-Madison Discussion Leader Chisholm, Malcolm Ohio State University Participant Clarke, Michael Program Officer, National Science


Covert, Katharine J. Program Officer, National Science Foundation

NSF representative

Cummins, Christopher Massachusetts Institute of Technology

New Fundamentals Group Leader

DeRose, Victoria Texas A&M University Bioinorganic Group Leader Dunbar, Kim Texas A&M University Participant Eisenberg, Richard University of Rochester Discussion Leader Espenson, James Iowa State Participant Gilje, John Program Officer, National Science


Goldberg, Karen University of Washington Participant Hartwig, John Yale University Catalysis Group Leader Holm, Richard Harvard University Discussion Leader Hoffman, Brian Northwestern University Co-PI Kauzlarich, Susan University of California, Davis Group Leader, Materials Lippard, Stephen Massachusetts Institute of

Technology Speaker

Long, Jeff University of California, Berkeley Participant Lu,Yi University of Illinois at

Urbana-Champaign Participant

Magyar, John Northwestern University Graduate Assistant Meade, Tom California Institute of Technology Participant Miranda, Raoul Department of Energy DOE representative


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Name Institution Role

Mirkin, Chad Northwestern University New Length Scales Group Leader

Neu, Mary Los Alamos National Laboratory Environmental Group Leader

Nocera, Daniel Massachusetts Institute of Technology

Participant

Peters, Jonas California Institute of technology Participant Que, Lawrence University of Minnesota Participant Robinson, Gregory University of Georgia Participant Sessler, Jonathan L. University of Texas at Austin Participant Spiro, Tom Princeton University Participant Stanley, George Louisiana State University Participant Hilary Arnold Godwin (P.I.) and Jillian Buriak (co-leader of Materials Group) were unable to attend the workshop, but contributed to the preparation of this report.


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Appendix III. Table of Contributions and Advances in Inorganic Chemistry Contributions in Core Topics

• Weakly coordinating anions • Enantiomorphic site control in single-site Ziegler–Natta catalysis • Fixed-distance electron transfer • Metal-metal multiple bonding in molecular systems • Frontier molecular orbital theory of organometallic reactions

Contributions in Materials Chemistry • High temperature superconducting copper oxides • Synthesis of new zeolites and application to industrial processes (e.g.,

hydrocarbon cracking) • Quantum dots and wires • Ferroelectric and dielectric materials • Novel magnetic materials (e.g., molecular magnets and colossal

magnetoresistive materials Contributions in Catalysis

• Olefin Polymerization Catalysts (e.g., Ziegler Natta) • Olefin Metathesis (e.g., Ring Opening Metathesis) • Carbonylation Reactions (e.g., hydroformylation) • Oxidation Catalysis (e.g., methane oxidation to produce MeOH)

Contributions in Bioinorganic Chemistry • Structure and Function of Key Metalloenzymes (e.g., cytochrome oxidase,

nitrogenase, methane monooxygenase, hydrogenase, sulfite reductase) • Insights into the role of metalloproteins in medical conditions (e.g., sickle cell

anemia, ALS) • Synthesis of small molecule models for Fe-S clusters, novel Cu, binuclear

models (Fe–Cu), Metallohydrolases (Ni, Zn), hydroxylases (Mo,W) • Anticancer therapeutics (Pt) • Contrast agents for imaging and diagnostics (Gd, Tc) • Metal pharmaceuticals as enzyme inhibitors • Elucidation of pathways and donor-acceptor partners in biological electron

transfer systems • De novo design of metalloproteins and peptides • New Discoveries That Lay the Basis for Future Research

o Role of metal homeostasis on disease o Biosynthesis of metal centers (i.e., urease) o Metals and prion disease o Metals and RNA (ribozymes)

Contributions in New Length Scales • Development of synthetic methods for quantum dots


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• Advent of scanning probe, electron beam, and nanosphere lithographies, • Templated syntheses for nanorods • ,Improved solution chemical methods for synthesizing metallic and

semiconductor nanoparticles Contributions in Environmental Chemistry

• Supercritical fluids – CO2 DuPont pilot plant for Teflon • Green catalysts for paper industry: peroxide oxidation • Battery technology—removal of cadmium • Elucidation of the Fundamental Reactions of CFC’s in the ozone layer • Ozone replacing chlorine in water purification


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Appendix IV. Table of Frontier Topics in Inorganic Chemistry Core Topics

• Implementation of automated database- and computer-aided methods for retrosynthesis and for the choice of particular strategies and reaction conditions

• New assembly methods • Inorganic retrosynthesis • Quantitative interplay between theory and experiment • Exploitation of inorganic secondary and tertiary structure • Beyond one-electron reactivity • Bond-Breaking and Bond-Making Processes • Thermodynamically unfavorable reactions • Manipulation of Kinetically Inert Molecules • Single-molecule –bond reactions • New bonds between atoms • Natural inorganic products • Non-traditional molecular feedstocks for atom and group transfer • Cascade reactions • High-energy reagents for inorganic synthesis • Exploratory synthesis and new synthetic methods

Frontiers in Materials Chemistry • Elucidation of phase space for synthesis of new materials • Development of molecular precursors • Preparation of complex materials with specific applications or functions (e.g.,

superconductivity; materials for microelectronics such as new barrier materials, ferroelectrics, dielectrics; photonic materials; magnetic materials; catalysts; and separation and sensor materials)

• Preparation and characterization of novel amorphous materials Frontiers in Catalysis

• Structure, dynamics and reactivity of highly unsaturated metal complexes • Role of new ligands in stabilizing unsaturated metal complexes • Better understanding of the role of cationic and electrophilic metal center in

catalysis • Use of higher oxidation state metal complexes in catalysis • New elementary reactions (e.g., nitrogen functionalization) • Heterogeneous catalysis • “Green” solvents (water, fluorinated, supercritical CO2, ionic liquids)


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• Homogeneous/heterogeneous interface o Controlled production of clusters/colloids with specific sizes and

compositions o New catalytic applications for nanosized clusters o New support strategies for heterogenizing homogeneous catalysts o New support strategies for nanosized clusters o Studying the transition region from molecular to bulk properties

• Theory o Improved theoretical techniques for better studying larger and more

complicated systems o Closer coupling of theory and catalytic experimental results to provide

better future guidance in designing new catalysts o Use of theory in understanding heterogeneous catalysis

• New polymerization and oligomerization reactions o Design of functional group tolerant catalysts o Smart polymers o Biodegradable/biocompatible polymers o Catalysts which can control chain growth

• Bioinorganic catalysis in synthesis o Bioinorganic enzyme mimics o Direct enzyme utilization

• Ligand Design o Modular ligands o Shape selecting architectures o New reaction environments o New metallic clusters

• Catalyst evolution • Programmable tandem reactions (or reaction networks)

Frontiers in Bioinorganic Chemistry • Biocatalysis

o Manipulation of small molecules N2, CO, O2, H2O, CH4, NO o Multi-e- reactions o Hydrolytic reactions o Relationship to green chemistries

• Design and Synthesis of Functional Models o New coordination chemistries o Unique functionalities (H-bonding, radicals) o Peptidomimetics o Engineering protein sites

• Mechanisms of biological cluster assembly • Metal trafficking

o Chaperones and insertases o Disease states


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• Electron transfer • Metals in medicine • Metalloenzymes with new activities

o Directed evolution o Active site engineering

• Metals and nucleic acids o Coordination modes o Ribozyme mechanisms

• Metalloneurochemistry • Biological NO chemistry • Sensors

o Coordination models for detecting metals in, ex vivo o Zn and Ca sensors for imaging metals in development, neurochemistry,

disease states o Biomolecules as metal sensors o Bioinorganic systems as biosensors (ex. redox-based sensors)

• Biomaterials o Biomineralization o Biomimetic materials o Adhesion

• Inorganic chemistry of the cell (‘metallome’) • Incorporating genomics into bioinorganic chemistry

o New metalloproteins with novel functions discovered from gene sequences o Chip detection of gene expression o Expression in response to (toxic) metals (Pb, Cd, Hg, Cr) o Metalloprotein expression related to development, disease, cell cycles o Metalloproteins involved in signaling o Metal ion homeostasis o New levels of biocomplexity

• Biomimetic chemistry o linked chemistry (sequential reactions, triggering) o scaffolds o combinatorial approaches o confined spaces o mesoporous solids, vesicles, nanotubes

• Environmental bioinorganic chemistry o Oceans o Extreme environments (vents) o Toxic metals (Pb, Se, As, Cd)

• Dynamics of metalloproteins o Motions related to catalysis o Docking


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Frontiers on New Length Scales

• Methods for controlling nanoparticle size, shape and purity • Correlation of particle size, composition, and structure with physical and

chemical properties • Surface functionalization – controlling physical properties via surface ligation

o Selective functionalization the faces of an anisotropic particle • New methods of characterization • Structure-function correlations

o Magnetic o Electronic o Optical o Ferroelectrics o Reactivity (e.g. Catalytic)

• Patterning, organization, and manipulation of inorganic nanostructures • Innovative uses for nanoparticle structures • Coordination chemistry approach to nanoparticle synthesis – nanomolecules • Nanotubes and nanowires • Theory --- Increase capacity for larger structures.

Frontiers in Environmental Chemistry • Interfacial phenomena • 3rd generation synchrotron-based techniques – applied to environmental

problems; grazing incident angle • Environmental restoration: dithionite reduction of pertechnetate • Imaging and microscopy • New media—SC fluids, ionic liquids • Complex and collective behavior (systems) • Biogeochemical theory and modeling • Separations (e.g., Moyer’s calixarenes) • Actinide remediation & sensing • “Toxic” metals in enzymes (e.g., Cd carbonic anhydrase) • Environmentally-friendly chemistry/ Impact free chemistry

o Pollution-free catalysts o aqueous catalysts o burning pollutants in water (PCBs to HCl & CO2) o Solvent-free reactions

• Inorganic chemistry in nature o C-1 chemistry; inorganic chemistry of CO2 o Iron in the oceans; carbon cycling o Biocatalysis o Nitrogen fixation o Photosynthesis


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• Water and Land remediation/water quality: o Bioinorganic remediation of oxoanions, (re-oxo chem. for ClO4

- reduction) o RCRA o Radionuclides o Sulfides from paper plants

• In-situ stabilization and monitoring o In-situ ‘stabilization’ and stewardship (cheaper remediation and

restoration) o Sensors for inorganics (actinides, anions, environmental metals); NOx o Time release and other ‘smart material barriers’ (i.e., dithionite); general

idea for use in stewardship of waste sites o Anion capture: arsenate, fluoride, pertechnate

• Theoretical and experimental modeling of environmental impacts o Development of new theoretical methods (tackle larger systems;

interdisciplinary systems)


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Appendix V. Evaluation Of Workshop By Participants I. Arrangements, Facilities, and Logistics

1. Communication from the organizers about travel arrangements prior to the workshop were:

Excellent Good OK Poor Comments: Didn’t use

2. Making travel arrangements through Northwestern Travel was: Excellent Good OK Poor Didn’t Use Comments: HAD INITIAL PROBLEMS

3. The choice of Copper Mountain as a meeting site was: Excellent Good OK Poor Comments: closer to airport

4. The meeting facilities at Copper Mountain were: Excellent Good OK Poor Comments: A BIT OUT OF THE WAY

5. The onsite staff at Copper Mountain were: Excellent Good OK Poor

6. The meals at Copper Mountain were: Excellent Good OK Poor


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Summary of responses to questions 1-6:

0

2

4

6

8

10

12

14

16

18

1 2 3 4 5 6

Question #

# of

resp

onse

s

Excellent

Good

OK

Poor

Didn't Use

7. The duration of the workshop was: Too short Somewhat short Just right Somewhat long Too long Summary of responses to question 76:

0

2

4

6

8

10

12

14

16

18

7

Question #

# of

resp

onse

s Too shortSomewhat shortJust rightSomewhat longToo long

8. The amount of free time provided was:

Too much Somewhat much Just right Almost enough Not enough


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9. The amount of time allocated for each breakout session was: Too much Somewhat much Just right Almost enough Not enough

10. The amount of time allocated for each panel discussion was: Too much Somewhat much Just right Almost enough Not enough

Summary of responses to questions 8-10:

0

2

4

6

8

10

12

14

16

18

8 9 10

Question #

# of

resp

onse

s

Too muchSomewhat muchJust rightAlmost enoughNot enough

11. Did you find the format of the workshop (breakout sessions and panel discussions as opposed to scientific talks) to be productive? Do you have any suggestions for how future workshops should be formatted?

Comments: MORE TIME FOR WRITING →TELL ALL PARTICIPANTS TO BRING COMPUTERS IF THEY HAVE THEM Fine. Would have to think about format changes. It depends the goal. This was the format of choice for generating a report. effective + productive format Panel + breakout format is OK* *Panel on funding mechanisms (PI vs. group) was unnecessary. That time could’ve been spent identifying future scientific challenges. Let Prog. Dirs./NSF device the best mechanisms and let the scientists discuss the science.


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Yes. Drop Directed/not directed Fundamental/applied Include “How can Inorg. Chemist. Better participate the existing initiative?” & “What are future initiatives that might critically involve Inorg. Fine. Would have to think about format changes. Yes (to 1) That would depend on the purpose of the workshops. There should be a point where breakout sessions take place for intermingling of participants from different groups. More time should be allocated for the write-up. Good FORMAT SEEMED TO WORK. The second breakout section on Sunday seemed to drag. I think there should have been a break at lunch time (perhaps 12-2) to allow for some outdoor recuperation! fine 1st Breakout and last could be longer. 2nd “ “ was too much time Yes yes Needed fuller discussion of the purpose of the panel reports. In the current format, it’s extremely difficult for one person to go to more than one breakout session and make significant contributions. 12. Do you have suggestions for sites for future meetings? (e.g., NSF headquarters, an airport

hotel/conference center, a site similar to Copper Mountain.)

Comments: Santa Fe


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DC conf. Center. Someplace close to an airport since in this format there is not much time

for leisure activities. Similar to Cu Mt. if more free time, otherwise closer to airport/easier transport Unless it is held during a weekday, I do not like using air-port hotel conference center

facilities. If there is no free time, then let’s have it @ an airport. Most of the time is spent wking, so I would focus on convenience (i.e., close to a major

airport, central location, etc.) No point in a place like Copper Mt. if we are inside all day. It would cost less & take less

time to be at a more accessible place. While it is nice to have a beautiful resort, the necessary travel time from the Denver Airport

makes travel planning difficult. I would prefer a resort hotel closer to a major airport. Site closer to an airport or with better access. No. DC Conf. center Someplace close to an airport since in this format there is not much time for leisure

activities. an airport location would be more time efficient. Copper was very nice but the extra 4 hours

commute time from the airport was not optimal and we really did not have much opportunity to enjoy the beautiful surroundings.

13. Do you have any additional comments or suggestions on facilities, accommodations, or logistics?

Comments:

Need more time for write-up, and a better distribution of participants. The group was weighted too heavily on the inorganic side of things. Shuttle was unnecessary. Several rental cars would have been better and less expensive. No.

John Magyar was great!


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II. The Workshop – Content

1. Before you arrived, what were your expectations for the format and content of the workshop?

Comments: None NOT WELL DEFINED Knew it would be a lot of work HAD LITTLE IDEA. To get a glimpse of major challenge that I hadn’t considered. Knew it would be a lot of work. More detail—schedule, etc.--helpful Largely unclear as to what would happen. not much, didn’t know what to expect Nothing. I was told nothing. None, since we were told not to prepare for anything. Expectations were general and diffuse. Not much expectation 2. Did the workshop meet your expectations? Please explain. Comments: I think it was stimulating. The outcomes will measure the real success, but I am optimistic Yes/no. Yes – disc. Were good. No – I’m worried there will be no impact Yes. Provided big picture of what is currently important & what will likely be important in


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Inorg. Chem. Yes, in the biosciences arena, not otherwise. APPROXIMATELY. I think it was stimulating. The outcomes will measure the real success, but I am optimistic. YES, IT WAS ABOUT WHAT I EXPECTED. THINGS WENT FAIRLY SMOOTHLY AFTER

OUR “BASICS” WERE DEFINED. Yes I found it exhausting and exhilarating Somewhat. Since I had no expectations, the workshop exceeded my expectations. It was a worthwhile

experience. Diffusiveness continued for much of the workshop. Ideas began to coalesce rather late. Yes. I am pleased we found a common scheme to work with. 3. What were the highlights of the workshop for you? Comments: First session It was Interesting to mingle w inorganic chemists w different backgrounds THE INITIAL GROUP DISCUSSIONS ON THE PAST + FUTURE DEVELOPMENTS Discussions during break-out sessions. Great people to work with. New ideas/insights for myself Finding out about all of the exciting new areas of chemistry and chatting with colleagues. Session 1


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Seeing what others in the field think of the future areas in the field. The opportunity to discuss what the hot topics of IC are. The chance to clarify some ideas about the future of the field. Chance to talk to colleagues. Consistency of viewpoints among different sectors of inorg chem in terms of future

challenges. Came up with the common scheme/buzz words. 4. Were there any low points? If so, what were they? Getting travel/food sick the first night Directed/nondirected None As stated in I-11, funding mechanism discussion did not add anything to the obvious. ILL-DEFINED DIRECTED VS. NON-DIRECTED CATEGORY Too short Only points of low energy! Session 2, but it was ok. good grp of people to talk with. The adjustment to high altitude should be considered. Slow start. Much milling around. 5. Were there additional topics that you felt should have been discussed at this workshop?

Should future workshops be organized to address these issues? More on theory More on organic/inorganic interface Theory Not more, but deeper discussions were needed* *Actually, more topics are needed:

• Theory • New instrumental methods


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I feet we were trying to make subjective policy in science. The target audience of the report was not clear.

6. Would you attend another workshop of this type? If so, how soon/ how often should they

be held?

The Inorganic community (ACS/DIC; MRS, SBIC, etc) must follow up on what was started here. Suggest joint NSF/DOE/NIH work-up in 2 y. Yes Yes 3-4 yr Not sure! Every five years Current format & practice of NSF proposal review. It has lots of problems. YES—EVERY FIVE YEARS. BUT I THINK YOU SHOULD TRY TO ROTATE

PARTICIPANTS AROUND!

Yes. POSSIBLY. Yes, in a couple of years it would be good to see what changes have occurred. Yes, but not too often. We have lots of other work. No more than once every ten years. Yes, perhaps once a year. If better focused Probably

7. How representative of the field of inorganic chemistry do you feel the participants in this

workshop were? With the exception of theory advocates, ok.


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Good Very good except for an underrepresentation of theory. A few more non-inorganic chemists, such as myself, would add to the mix. VERY GOOD! NO HETEROGENEOUS CATALYSIS TYPES, HOWEVER. Good => more theory & heterogeneous cat. People needed. NOT ENOUGH PARTICIPANTS IN THE AREAS OF NEW LENGTH SCALES AND MATERIALS. Good representations. Broad and expert Nice cross section of interests Very broad representation. O.K. It was quite representative. very well. good choices Representative 8. Do you have any suggestions for how participants should be selected for further

workshops? Solicit suggestions from NSF, DOE, NIH etc. Include a few outstanding people from smaller schools. At least some returnees from this one More industrial representation OPEN CALL + A SELECTION COMMITTEE TO PICK PARTICIPANTS. MORE ADVERTISING IN THE FUTURE!! No, the process was fair. As long as you make sure that the age distribution & field interests are diversely represented. No, …


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Select with specific assignments in mind.

9. Did you or your friends/colleagues have concerns about the workshop (e.g., format, content, organization, mission) before you came to Copper Mountain? What were they? After having attended the workshop, do you consider these concerns to be valid? How could they be best addressed in the report or at future workshops?

Concerned that everyone would push their own rsch area. Organizers were clear in avoiding this. My family didn’t like the lost of husband/daddy for the weekend! COPY OF PREVIOUS REPORT TO PROVIDE GUIDE FOR NEW REPORT. There were concerns because of the title. Needs to be made clear to the IBO community what is at hand. No Of course, people worry about a subset dictating the future. Valid concern. Ask people for written statements like we prepared on Mon AM. Yes. The purpose of the workshop was not clear. If the mission is to bring more money to inorganic chemistry, then we should unite & get the job done. Many of my colleagues felt that should be the goal. Purpose wasn’t very clear. More material in advance would have helped. Fuller discussion of purpose would have helped. 10. Are there any other insights or suggestions that you would like to share with us? (Use

other side if necessary.) The report should capture peoples’ imagination! PR and follow up is essential.


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Appendix VI. Summary of Workshop Expenses


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Documents

The Frontiers of Inorganic Chemistry 2002jtchen/20030926_Frontiers...2003/09/26 · the ways in which Inorganic Chemistry plays a major role in all aspects of modern life. A summary