Developing carborane-based functional polymeric architectures

University of Massachusetts Amherst University of Massachusetts Amherst

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Doctoral Dissertations 1896 - February 2014

1-1-2008

Developing carborane-based functional polymeric architectures. Developing carborane-based functional polymeric architectures.

Yoan C. Simon University of Massachusetts Amherst

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DEVELOPING CARBORANE-BASED FUNCTIONAL POLYMERICARCHITECTURES

A Dissertation Presented

by

YOAN C. SIMON

Submitted to the Graduate School of the

University of Massachusetts Amherst in partial fulfillment

of the requirements for the degree of

DOCTOR OF PHILOSOPHY

September 2008

Department of Polymer Science and Engineering

UMI Number: 3336993

Copyright 2008 by

Simon, Yoan C.

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by

YOAN C. SIMON

Approved as to style and content by:

E. Bryan Coughlin, Chair

Todd S. Emrick, Member

Anthony D. Dinsmore, Member

Shaw-Ling Hsu, Head




by

YOAN C. SIMON

Approved as to style and content by:

Todd S. Emrick, Member

Anthony D. Dinsmore, Member

Shaw-Ling Hsu, Head


DEDICATION

To my belovedfamily. .

.

ACKNOWLEDGMENTS

First of all, I would like to express my gratitude and appreciation to my advisor.

Prof. E. Bryan Coughlin. Through his encouragement and constant optimism, Bryan has

always found a way to motivate me even in the darkest hours and has helped me

overcome the different hurdles of my PhD. His guidance and excitement for research

have been very inspiring and have encouraged me to pursue a career in academia. I

would also like to acknowledge Prof. Todd Emrick and Prof Anthony Dinsmore for

serving on my committee. 1 have learned a lot through their insightful comments and

constructive criticism. I hope to make good use of their scientific advice in my future

endeavors. Additionally, Todd has been a great mentor, a great basketball teammate and

a knowledgeable wine connoisseur. I would like to thank Tony for his kindness and

willingness to support me in my various scholarship applications. Generally speaking, I

am extremely grateful to all three of my committee members for all their help and

availability. They have been truly instrumental in my search for a postdoctoral position

and I am truly indebted to them.

All faculty members in the PSE department have had a major impact on my

vision of science but I would like to specifically express my gratitude to Prof Harry

Bermudez for his invaluable advice on career and his help in the various aspects of my

relocation to Switzerland. We have collaborated with Prof. Ken Carter on a number of

different projects and I want to emphasize how pleasant it has been working with him.

Also, 1 might have never come to UMass if it was not for Prof Jacques Penelle's help

and I need to thank him warmly for his contribution to my education.

Special thanks go to Dr. Charles Dickinson and Dr. Weiguo Hu for teaching me

about NMR and making my czar duties much easier. Dr. Stephen Eyles, Dr. Greg

Dabkowski and Dr. Sekar Dhanasekaran have all played a very important role in

keeping the facilities up and running, and I am truly appreciative of their work,

knowledge and pleasant conversation. I also need to pay tribute to the administrative

staff for their fantastic, and too often overlooked, job.

Before I go into thanking profusely the members of the Coughlin group who

have been outstanding professionals and amazing friends, I would like to acknowledge

the kindness and compentency of my fellow students and postdocs in the department. I

would particularly like to express my appreciation to all of the people on the sixth floor

who have helped me scientifically, and cheered up my days in our conversations in the

hallway. Same goes for all of my classmates. Additionally, I would like to express my

gratitude to the members of the Carter group who have been an extended branch of my

research group, my "home away from home". Notably, I want to thank Joe and Isaac for

our fruitful collaborations and for their friendship.

All of the Coughlin group members, past and present, have played an

instrumental role in my stay in Western Massachusetts. Firat, Push, Greg, Ramon,

Jeanette, Nui have been among the first to welcome me and help me settle in the group.

I have inherited Raji's space but I have gotten much more from her. Her kindness and

sagacious career advice have been very important to me. Brad has been a great

basketball teammate and a great pal who taught me many things about American pop

culture and sports. It has been a privilege to work alongside Bon-Cheol, Tarik, Chris

and Liz, and to collaborate with three great students from Mainz: Christian, Melanie

vi

and Christine. More generally, I want to thank all ofmy group members for coping with

my questions about how to say this or that in a foreign language, particularly, Shilpi,

Ying and Makoto-san who had to deal with my fascination for eastern languages. Ranga

also helped me in these endeavors. He has been a true inspiration as a very skilled

chemist, a great cook and an awesome friend. It has been a real treat to join the group at

the same time as Rich who has been a role model for me, and with whom I shared great

moments in B666. Whether it was about column chromatography, music, or le Tour de

France, he has always been a very fun person to talk to. I also made three genuine

friends during my stay in the group. I will really miss my endless conversations with

Sergio and Gunjan about science. 1 will also miss their opinionated views about politics,

life and culture, or whatever subject they felt like talking about that day. I already miss

talking to my fellow French compatriot, Gregoire, who has left for warmer horizons. He

has been a piece of France in Western Mass, a real guide for me, a veritable friend.

These tliree muskateers will stay dear to my heart.

I must also thank all of the microbiology crew Dave, Dmitry, Jeff, Kimmie and

Cathy for their support and friendship. My stay here would never have been the same

without them. I want to thank my friends from the dorms and from Europe, and I have a

particular thought for my friend Lionel, who left us too quickly. I also need to express

my attachment to my roommates: Wei, Bing and Bemabe. They were my surrogate

family for one year and I truly cherish the times that we had together.

I want to express my gratitude and affection to all the members of my family

who have always been very supportive and have provided me with the love that I

needed (even when they did not understand why 1 was staying in school for so long). I

vii

want to share this accompHshment with them, as it is also the fruit of their labors in my

upbringing. In spite of the distance, my parents, Lionel and Annie, and my brother

Yannick have always been there for me, and I can never stress how appreciative I am.

Nicky has been more than just a sibling all these years; he has been my accomplice and

my friend. His wit, kindness and brotherhood have empowered me. I would have never

become a researcher if it was not for my father's affection, inspirational curiosity and

his incredible attention to detail. His openmindedness for other people's culture is the

very reason why I came to the United States. I could have never become a researcher,

had I not been nurtured my mother's perseverance and patience. Her love and

encouragement could help me overcome anything.

Finally, I need to reserve an entire paragraph for my love, Emily. Em, it has

been a true honor to share my life with you for the past four years, and I am looking

forward to the many years to come. Meeting you was the best thing that could happen to

me. You have been my best friend and my confident. From delicious meals you

prepared to the mundane tasks of life, you have brightened up every minute of my stay

here. I can never thank you enough for your support, your patience and your love.

viii

ABSTRACT


SEPTEMBER 2008

YOAN C. SIMON,

DIPLOME DTNGENIEUR, ECOLE NATIONALE SUPERIEURE DE CHIMIE DEMONTPELLIER, FRANCE

Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST

Directed by: Professor E. Bryan Coughlin

The research presented in this thesis focuses on the development of novel

functional hybrid organic-inorganic architectures containing chemically-tethered

icosohedral carboranes. The motivation behind this work was to understand and

overcome the challenges associated with the incorporation of inorganic boron clusters

into a variety of well-defined polymeric architectures. This task was critical for the

advancement of scientific understanding, as well as the improvement and

implementation of novel hybrid materials towards technological applications. Chapter 1

illustrates some of these potential target applications, and highlights the advantages

associated with the utilization of hybrid materials, in particular those containing boron.

The synthesis of a novel silyl-protected oxanorbomene imide carborane

(SONIC) monomer as well as its copolymerization by ring-opening metathesis

polymerization (ROMP) to obtain amphiphilic diblock copolymers is described in

Chapter 2. The subsequent ftinctionalization and labeling of the polymers, and their

solution behavior have been investigated. Initial biological studies have shown the

ix

incorporation of the carborane-containing polymers in carcinoma cells. These findings

pave the way for future investigations of these polymeric architectures as delivery

agents for boron neutron capture therapy in cancer treatment.

The random copolymerization of SONIC and cyclooctene is reported in Chapter

3. Polymers with varying compositions have been obtained and hydrogenated to afford

polyethylene-like materials. The structural and thermal properties of these materials

have been evaluated and compared to model compounds.

Carboranes have also been introduced into conjugated polyaromatic structures

as side chains. The synthesis of a polyfluorene monomer having two pendant

silylcarborane groups is reported in Chapter 4. The homopolymerization of this

monomer, and its copolymerization with 2,7-dibromo-9,9-di-/7-hexylfluorene by

microwave-assisted nickel(0)-mediated coupling was investigated. The advantage

offered by the presence of bulky silylcarborane groups is described.

Finally, the versatility of carborane-containing polymers is demonstrated

through their utilization as resists for nanoimprint lithography (NIL). A novel

silylcarborane-containing aerylate has been synthesized as described in Chapter 5. The

utilization of only 1 0 wt% of the carborane-containing resist lead to a two-fold decrease

in etch rate. Excellent image transfer was also observed, allowing for the fabrication of

gold interdigitated electrodes. This work provides a new set of tools for the efficacious

implementation of NIL.

X

TABLE OF CONTENTS

Page

ACKNOWLEDGMENTS v

ABSTRACT ix

LIST OF TABLES xiv

LIST OF FIGURES xv

LIST OF SCHEMES xviii

LIST OF ABBREVIATIONS xix

CHAPTER

1 INTRODUCTION 1

1.1 Hybrid Organic-Inorganic Materials: How to Tailor Architectures to

Benefit from Both Counterparts 2

L 1 . 1 Relevance and Synthetic Strategies 2

L 1 .2 Applications of Hybrid Nanocomposites 6

1.1.3 Opportunities for Research 7

1.2 Introduction to Boron, Boron Clusters and Their Applications 8

1.2.1 Carboranes and Boron Clusters 8

1 .2.2 A Brief Overview of Possible Applications 1

4

1 .2.3 A Review of Previous Literature on Carborane Polymers 1

9

1 .3 Outline of the Dissertation 22

1.4 References 23

2 AMPHIPHILIC BLOCK COPOLYMERS FOR BORON NEUTRONCAPTURE THERAPY 28

2.1 Introduction 28

2.2 Route A: Polymerization Using a Protected Amine, Deprotection and

Subsequent Functionalizations 29

2.2.1 Experimental Section 29

2.2.2 Results and Discussion 38

xi

2.3 Route B: Using PEGylated Norbomene Esters 47

2.3.1 Experimental Section 47

2.3.2 Results and Discussion 49

2.4 Conclusions 50

2.5 References 51

3 RING-OPENING METATHESIS COPOLYMERIZATION OFCYCLOOCTENE AND A CARBORANE-CONTAININGOXANORBORNENE 54

3.1 Introduction 54

3 .2 Experimental 55

3.2.1 Materials 55

3.2.2 Instrumentation 56

3.2.3 Synthesis and Spectral Data 57

3.3 Results and Discussion 59

3.3.1 Copolymerization 59

3.3.2 Hydrogenation 62

3.3.3 Thermogravimetric Analysis 64

3.3.4 Wide-Angle X-ray Scattering (WAXS) 66

3.4 Conclusions 70

3.5 References 70

4 SYNTHESIS OF POLYFLUORENES WITH PENDANTSILYLCARBORANES 72

4.1 Introduction 72

4.2 Experimental Section 74

4.2.1 Materials 74




4.4 Conclusions 84

4.5 References 85

5 DEVELOPMENT OF SILYLCARBORANE MONOMERS FORLITHOGRAPHY 87

xii

5.1 Introduction 87

5.2 Experimental Section 90

5.2.1 Materials 90




5.4 Conclusion 101

5.5 References 102

6 CONCLUSIONS AND RECOMMENDATIONS 1 04

6.1 Dissertation Summary 104

6.2 Future work 107

6.2. 1 Materials for BNCT 1 07

6.2.2 Influence of the silyl-protecting group and utilization in

radiation shielding applications 1 09

6.2.3 Polyfluorenes with carboranes in the backbone 1 1

3

6.2.4 Novel high-boron content resists for EUV lithography and

nanoimprint lithography 115

6.3 Final word 1 1

7

6.4 References 118

APPPENDICES

A BORON NEUTRON CAPTURE THERAPY AND ENHANCEDPERMEABILITY AND RETENTION 1 19

B RADIATION SHIELDING 1 26

BIBLIOGRAPHY 132

xiii

LIST OF TABLES

Table Page

2.1 Tabulated data for the homopolymerization of SONIC 39

2.2 Tabulated data for the copolymerization of SONIC 4 and BONIA by

ROMP 40

3.1 Conditions and results for the polymerization of monomers 4 and COE 62

3.2 Hydrogenation results for the polymers 5 and 12 synthesized in

dichloromethane 64

3.3 Thermogravimetric analysis and differential scanning calorimetry results of

12, H-12, Hand H-14 66

5.1 Imprint and etch profilometry results 98

xiv

LIST OF FIGURES

Figure Page

1.1 Examples of hybrid materials in nature: (a) Diatom: eurkaryotic algae with a

silicate wall (image from Ref. [2]), (b) Enamel and dentin in teeth (image

from Ref. [9]), (c) Seashell nacre (image from Ref [10]) 3

1.2 Design of hybrid organic-inorganic materials from various nanobuilding

blocks (image from Ref. [2]) 4

1.3 Examples of self-assembly from micellar and polymeric structures (image

from Ref [13]) 6

1.4 Examples of metallacarboranes (image from Ref. [25]) 10

1 .5 Synthesis of o-carborane by coupling of acetylene with decaborane 11

1 .6 The three isomers: o-, m-, p-carboranes 12

1.7 Size analogy between carboranes and phenyl rings (image from Ref [25]) 13

1.8 Examples of carriers 14

1.9 Research towards ion exchange membranes radioactive 15

1.10 Representations of unsubstituted [12]mercuracarborand-4 (left) and

[9]mercuracarborand-3 (right) 16

1.11 Illustration of the non-coordinating properties of the monocarbaborane,

formation of a silver complex (image from Ref. [68]) 16

1.12 Hafnium catalyst for alkyne hydrogenation 1

7

1.13 Liquid crystals and self-assembly. An example of possible liquid-crystalline

structure (top), clusters self-assembly (bottom, image from Ref. [69]) 18

1.14 Cycles and rods. Macrocycles containing carboranes (top). B) Illustration of

the staggered morphology observed by transmission electron microscopy

(bottom, image from Ref [71]) 19

1.15 Examples of polymers with carboranes in the backbone 20

1.16 Examples of polymers containing carboranes as pendant groups 21

1.17 Reported examples of quasi-living polymerizations for the design of

macromolecular architectures embedding boron clusters by ATRP 22

XV

2.1 Synthesis of the SONIC monomer 3. TBDMS: /erbutyldimethylsilyl. DIAD:

diisopropylazodicarboxylate 35

2.2 Ring-opening metathesis polymerization and subsequent amine deprotection

syntheses. TBDMS: /er/-Butyldimethylsilyl, TFA: Trifluoroacetic acid 37

2.3 Post-polymerization modifications 38

2.4 GPC chromatograms in THF of poly(SONIC) (solid line, PDI = 1.08, Mn =

37 kg/mol) and poly(SONIC-^-BONIA) (dashed line, Entry 6v, PDI =

1.11 Mn = 65 kg/mol) 41

2.5 Illustration of the appearance of the ammonium peak at 8 ppm 42

2.6 Distribution of sizes measured by dynamic light scattering (left) and atomic

force microscope image (right) of micellar aggregates (Entry 6v) .....43

2.7 'H NMR experiment illustrating the solvents of different polarities 44

2.8 Confocal microscopy image of HEp-2 carcinoma cells after a 22h incubation

period 47

2.9Triblock copolymer formation and labeling 49

2.10 RI (left) and UV (right) GPC chromatograms of 10 and 11 50

3.1 Ring-Opening Metathesis copolymerization of 1 and COE 59

3.2 Illustration of the differences in alternation depending on solvent polarity 60

3.3 Conditions for the hydrogenation of polymer 12 63

3.4 Proton NMR spectrum of H-12(25)-D 63

3.5 Synthesis of model polymers 14 and H-14 to evaluate the influence of the

silylcarborane cage on thermal properties 65

3.6 Wide angle X-ray scattering results for the series of polymers 3 68

3.7 Wide angle X-ray scattering results for the series of polymers H-12 69

4.1 Synthesis strategies to attain monomer 17. i. CH2CI2, TsCl,

pyridine(dropwise); ii. CH2CI2, 0 °C, CBr4, PPha; iii. THF, tBuOK, 2,7-

dibromofluorene; iv. PhH/Et20 (2:1 V:V), tBuOK, 2,7-dibromofluorene 74

4.2 'HNMR ofhomopolymer 18(100) 79

4.3 ^HNMR ofhomopolymer 18(50) ..79

xvi

4.4 Microwave assisted polymerization of 17: (a) homo and (b) copolymerizations

with 2,7dibromo-dihexylfluorene 81

4.5 Gel permeation chromatograms for polymers 18(100) and 18(50) 82

4.6 UV absorption (left) and emission spectra (right) for polymers 18 83

5.1 Synthesis of the silylcarborane aerylate 19 95

5.2 Components of the photopolymer solution (Formulation A) 96

5.3 Determination of etch rates of the control formulation (A) and the modified

(B) resists 97

5.4 Bar chart for visual aid of depth amplification from etch resists A and B 98

5.5 Imprinted and etched device features. On the left are features patterned into

unmodified formulation A (i) and (iii), on the right are the same features

patterned into formulation B, (ii) and (iv) 99

5.6 Patterned gold features, (i) Unresolved interdigitated electrodes using

formulation A as an imprint layer (top) and (ii) using the B resist resolved

patterns are observed (bottom) 100

6.1 Synthetic strategy towards biodegradable BNCT agents 109

6.2 Deprotection of the hydrogenated polySONIC H- 12(1 00). Schematic(top)

and GPC chromatograms (bottom) Ill

6.3 'H NMR spectrum of H-2 1 .* Solvent impurity 112

6.4 Alternative route to obtain deprotected carborane polymers 1 13

6.5 'H NMR spectrum of monomer 20 113

6.6 Synthesis of monomers incorporating carboranes along the backbone.

Sonigashira conditions: (Ph3P)2PdCl2, Cul, EtiNH 114

6.7 'H NMR spectrum of intermediate 22 116

6.8 'H NMR spectrum of intermediate 22 117

A.l Schematic of the elimination of diseased tissues using BNCT 121

A.2 Schematic of the principles of the EPR effect (image from Ref. [8]) 123

B. l Efficiency of blends of '^B and polyethylene and other materials for neutron

shielding (image from Ref [10]) 130

xvii

LIST OF SCHEMES

Scheme Page

3.1 The perfectly alternating structure of polymer 12(50) 60

5.1 Illustration of the use of an etch-resistant imprint layer for pattern

amplification in metallization processes 90

5.2 Comparative schematic illustrating the mechanism by which the patterns are

obtained. The brown layer represents the silicon wafer, the gray layer is

the imprint layer and the top layers are the two respective types of

formulations 101

xviii

LIST OF ABBREVIATIONS

AFM Atomic force microscopy

AIBN Azobisisobutyronitrile

ATRP Atom transfer radical polymerization

BNCT Boron neutron capture therapy

Boc Butoxycarbonyl

BONIA Boc-protected oxanorbomene imide amine

COD Cyclooctadiene

COE Cyclooctene

DAPI 4',6-Diamidino-2-phenylindole

DCM Dichloromethane

DIAD Diisopropylazodicarboxylate

DLS Dynamic light scattering

DMF Dimethylformamide

DMSO Dimethylsulfoxide

DPn Average degree of polymerization

EPR Enhanced permeability and retention

EUV Extreme ultra-violet

FBS Fetal bovine serum

OCR Galactic cosmic rays

GUI Grubbs' third generation catalyst

GPC Gel permeation chromatography

HEMA Hydroxyethylmethacrylate

HEp Human epithelial

ICP Inductively Coupled Plasma

ISS International space station

Mn Number average molecular weight

NBB Nanobuilding blocks

NBD Nitroxybenzoxydiazole

NHC N-heterocyclic carbene

NHS N-hydroxysuccinimide

NMR Nuclear magnetic resonance

PDI Polydispersity index

PEG Polyethylene glycol

PF Polyfluorene

PGMEA Propylene glycol methyl ether acetate

PHEMA Poly(hydroxyethylmethacrylate)

PLED Polymer light emitting diode

PMDS Pentamethyldisilyl

POSS Polyhedral oligomeric silsesquioxane

ppm Parts per million

PVDF Poly(vinyldifluorine)

RBE Radiobiological effectiveness

RIE Reactive ion etching

ROMP Ring-opening metathesis polymerization

XX

SEP Solar energetic particles

SONIC Silylprotected oxanorbomene imide carborane, monomer 4

TBAF Tetra «-butylammonium fluoride

TBDMS Tert-butyldimethylsilyl

TFA Trifluoroacetic acid

TsCl Tosyl chloride

UV I Iltra-violpt

WAXS Wide-angle X-ray scattering

wt% Weight percent

xxi

CHAPTER 1

INTRODUCTION

Materials have always had a pivotal role in the evolution of civilizations. They are

actually so vital for the sake of societies that some of them have been used to classify

certain prehistoric periods, namely the Stone Age, the Bronze Age, and the Iron Age. If

one was, however, to name this modern day era for a type of material, it would certainly

be polymers. Since the term macromolecule was first coined by Staudinger in the early

1920s,[l] the success of commodity plastics and specialty products derived from polymer

chemisty has been staggering. From the car industry to home appliances, polymeric

materials have revolutionized our lifestyles.

That is why, at a time when an increasing number of functional materials are

needed to address the worldwide energy crisis, water decontamination or the challenges

associated with the advent of the communication era, it is only natural to believe that

some of these answers will come from the field of soft-matter chemistry. Nevertheless, it

would be pretentious to think that these challenges can be solved single-handedly by

seeking immediate results. This quest for new functional materials needs to be global and

thorough efforts to explore novel materials, sometimes, simply for the sake of acquiring

new scientific knowledge upon which major advances could be built. This foreword is

meant to illustrate the approach that was taken here, where novel hybrid inorganic-

organic materials were designed with a fundamental perspective but whose potential field

of applications is remarkably wide. The present chapter describes the properties and

1

advantages of hybrid inorganic-organic materials as well as some of the particular

characteristic of boron and boron clusters.

1.1 Hybrid Organic-Inorganic Materials: How to Tailor Architectures to Benefit

from Both Counterparts.

1.1.1 Relevance and Synthetic Strategies

From bones to seashells to teeth, nature displays a multitude of examples of

hybrid materials in which an organic and an inorganic part are synergistically united to

assume a specific function. Consequently, synthetic hybrid materials containing an

organic and an inorganic component have been contemplated as potential candidates for

fiinctional materials. [2] The possibility to benefit from the advantageous conjunction of

both counterparts is not foreign to the development of this class of materials.

Traditionally, the organic part provides the modularity and the flexibility to these

materials, whereas the inorganic part confers the robustness. However, the inorganic part

offers much more than mere reinforcement. It offers the possibility to explore areas such

as magnetism, optical quantization effects or electroactivity.[3-7]

In order to put the present study in context and understand its implications, it is

important to define the different types of hybrid materials and to highlight the diverse

approaches to obtain these. Sanchez et a/. [2,8] have reviewed the design of organic-

inorganic nanocomposites from various nanobuilding blocks (Figure 1 .2). There, hybrids

are classified into two categories Class I and Class II, that can be obtained via four types

of synthetic strategies, paths A through D.

2

Figure 1.1 Examples of hybrid materials in nature: (a) Diatom: eurkaryotic algae

with a silicate wall (image from Ref. [2]), (b) Enamel and dentin in teeth (image

from Ref. [9]), (c) Seashell nacre (image from Ref [10])

Class I illustrates a category of materials where neither covalent bond nor iono-

covalent bond (highly polarized bond that has intermediate properties between a classical

covalent bond and a pure ionic bond) exist between the two entities forming the

composite. In these hybrids, the different components of the material are held together by

weak interactions such as dipole-dipole interactions or Van der Waals forces. Class II

refers to covalently or iono-covalently attached amalgamates, the main focus of this

study.

Path A encompasses soft chemistry methodologies such as sol-gel chemistry or

the utilization of multifunctional precursors and hydrothermal synthesis. These

methodologies, while very interesting for their low cost and ease of implementation, offer

relatively limited control in terms of directed assembly. Path B relies on the utilization of

nanobuiliding blocks (NBB). As indicated by their name, NBB are inorganic clusters

upon which bigger architectures can be built. They can be used in assembly techniques as

nanometric bricks, in which case the organic component can be viewed as the mortar

keeping the inorganic components together, or in dispersive routes where they are

distributed in an organic matrix. Path C is the so-called self-assembly or bottom up

approach, which combines elements of the two previous routes, but whose main objective

3

resides in the controlled assembly of the different parts via the use of templates

(surfactants, block copolymers, etc.) and/or specific interactions. Finally, Path D is an

integrative approach which combines these nanometer-scale directed assemblies with

micron-scale shape control (colloidal masks, interfacial assembly) to obtain hierarchical

structures.

Figure 1.2 Design of hybrid organic-inorganic materials from various nanobuilding

blocks (image from Ref.[2]).

The necessity to investigate self-assembled structures, i.e. structures obtained

from the bottom-up approach, becomes apparent when observing natural systems. Rather

than utilizing extremely complex functionalities, nature has opted for a much more

elegant route,[l 1] wherein a limited number of building blocks are used and assembled in

particular conformations. Therefore, the specific functionality does not arise from the

4

intricacy of tiie building blocks themselves, but rather from the complexity of their

arrangement. The use of inorganic NBB in an organic matrix to direct self-assembly

results from a simple observation. Reproducing, with high fidelity, controlled structures

over several orders of magnitude lengthwise when the only tool at hand is the organic C-

C bond (~ 1.5 A) is no easy task. For that very reason, embedding, within an organic

matrix, well-defmed inorganic structures of larger size than the C-C linkage is an

appealing tactic. Conversely, it is extremely hard to gain control over monolithic

inorganic architectures. Their fabrication process (crystallization, condensation, etc) does

not allow an accurate rendition over vast domains. That is why an intermediate strategy

involving nanobuilding blocks comprising a reactive organic end bound to an inorganic

core of uniform size is highly valued. Other work has demonstrated the use of organic

scaffolds (block copolymers, vesicles, liposomes) to direct the assembly of inorganic

materials. [12]

5

I.aAM

Figure 1.3 Examples of self-assembly from micellar and polymeric structures (image

from Ref. [131).

1.1.2 Applications of Hybrid Nanocomposites

The utilization of hybrid materials is not a novel idea; the paint and polymer

industries have used them for decades in the form of pigments and fillers. [8] However,

with the growing desire to impart functionalities in novel materials, the interest in

nanocomposites has grown unabated. Aside for the evident advantage of benefiting from

the inorganic and organic components, the success of nanocomposites is a direct result of

their geometry. By decreasing the size of the inorganic part, the surface to volume ratio

increases. In doing so, the amount of interface between the two constituents is increased

dramatically leading to novel properties. The best example of this success of this

miniaturization effect is quantum dots. By reducing the size of the inorganic nanocrystals,

the energy levels become discretize, leading to unique electronic and optical properties

directly correlated to the size of the inorganic component. [14] However, in order for

quantum dots to have a practical application, they need to benefit from the dispersing

6

power of organic ligands. In particular, there has been a lot of interest in the utilization of

polymers, by grafting from or grafting to approaches, to achieve this goal. [15]

The second and maybe more obvious application of hybrid materials is

mechanical reinforcement. A variety of nanoscale inorganic fillers have been utilized to

toughen polymers from nanoparticles, to nanoclay or metal-oxide nanoclusters.[3]

Additionally, the modes of incorporation of these inorganic fillers has been incredibly

varied from very conventional mixing and methods to exfoliation methods to the use of

supercritical carbon dioxide to infuse polymeric matrices. Recent work by Gauckler et al.

has illustrated the possibility of mimicking biomaterials to obtain tough yet ductile

polymeric hybrids. [16] This work exemplifies the power of utilizing hybrid

nanocomposites to master the mechanical properties of materials.

The functions presented in this section are by no means an exhaustive inventory.

In fact, the list of applications already on the market is impressive: high-performance

coatings, biomaterials, electo- and optically-active materials, high-temperature seals, etc.

These examples illustrate the advantage of hybrid systems and the necessity for further

fundamental studies.

1.1.3 Opportunities for Research

Hybrid materials are clearly interesting and warrant further investigation. The

previous two subsections (1.1.1. and 1.1.2.) have highlighted the various pathways to

obtain organic-inorganic nanocomposites and the applied motivations. However, rather

than focusing on a specific application and constraining one's horizons, identifying a type

of inorganic material that has great potential, but whose utilization in hybrid polymeric

7

systems has been thus far very limited, promises to be far more interesting. To facihtate

this investigation, it is essential to have systems that are easily characterized.

Consequently, path B (Figure 1.2.) is a very attractive tactic, in that it offers the

possibility to utilize well-defined NBB with no distribution of size and with limited

reactivity. Additionally, the best way to control the incorporation of these NBB is

through their covalent attachment to a reactive handle {class IT). The strategy adopted

here revolves around the covalent tethering of boron hydride clusters to polymerizable

units with the view to acquire new functional polymeric architectures.

1.2 Introduction to Boron, Boron Clusters and Their Applications

1.2.1 Carboranes and Boron Clusters

1.2.1.1 Boron

Boron is a fascinating element that owes its name to the first ore discovered:

borax from the Arabic buraq, meaning white. Having many interesting features, it is

surprisingly one of the simplest elements in the periodic table. Its atomic number is 5

leading to the electron shell configuration Is 2s 2p. It has a standard atomic mass of

10.81 1 g.mol"' due to the presence of two isotopes "B (80.22%) and '^B (19.78%). It is

part of the second period and belongs to Group III of Mendeleyev's classification. The

only non-metal of its group, boron is part of the metalloid category along with Si, Ge, As,

Sb, Te and Po.

Borax ore, also referred to as fincal, (Na2B407- IOH2O) coexists with other types

of boron minerals like kemite, ulexite or colemanite.[17] All of the above are hydrated

versions of boric acid originating from former volcanic activity. The main extraction sites

8

are located in California, Nevada, Turkey, Argentina and Russia. The abundance of boron

in the earth crust is estimated at approximately 1 0 ppm.

The discovery of the element is attributed to Sir Humphry Davy (UK), Joseph-

Louis Gay-Lussac (Fr) and Louis Jacques Thenard (Fr) in 1808, and its subsequent

purification to Henri Moissan (Fr) in 1892. Boron appears under different forms as a

"pure'' material (P-rhombohedral, a-tetragonal, etc), as borates (tincal, rasorite, etc),

borides (B4C, Mg2B, etc), boron halides (BF3, BCI4") and boranes. In this study, boron

clusters, boron hydrides and boranes will be used interchangeably.

1.2.L2 Nomenclature of Boranes and Carboranes.

Based on the initial work by Alfred Stock et <3/.[18] in the early 1910's, the

chemistry of boron hydrides (BpHm) has spread remarkably and has become a science of

its ovm, at the border between organic and inorganic chemistry. Given its success and

uniqueness, boron cluster chemistry soon established its own philosophy and

nomenclature. This revolutionary remodeling led to the award of the Nobel Prize to

William N. Lipscomb in 1976 for the "studies of boranes which have illuminated

problems of chemical bonding". [19]

The borane continuum (BnHm) can be classified in 5 general subcategories: [17,20]

• c/o5o-boranes (from the Greek cage) comprise a series of fully closed

polyhedra formed of deltahedral faces.

• «/Jo-boranes (from the Latin nest) designate non-closed structures

resulting from the removal of one vertex from a corresponding closo

architecture.

9

• arachno-borams (from Greek spider's web) emanate from the withdrawal

of one of the vertices contiguous to the open face in a nido structure.

• hypho-horanQS (from Greek net) characterize clusters with the greatest

aperture proceeding from the same iterative vertex removal process.

• conjuncto-boranes (from Latin joining) results from any condensation of

the abovementioned entities.

These geometries can be typically predicted by Wade-Mingos's rule,[21,22] an

extension of molecular orbital theory. Carboranes, metallaboranes and metallocarboranes

are spin-offs of boron hydride chemistry. [23,24]

• C.CH •BH. B R=We. &S)*»

cr

M = Ta.Nb f.f = Fe.C5c

Figure 1.4 Examples of metallacarboranes (image from Ref. [25]).

1.2.1.3 Properties of Closo-Carboranes

In addition to their proximity in the periodic table, carbon and boron share many

common features. [26] For instance, boron hydrides or boranes are the analogs of

10

hydrocarbons or alkanes. Certainly, because of its ubiquity in living organisms and the

simplicity of its bonding patterns, carbon has overshadowed its "next-case" neighbor.

Beyond the intrinsic capacity of boron to self-catenate, carboranes (discovered in

1959 by R.E. Williams and CD. Good)[27,28] illustrate this remarkable asset of boron to

covalently bind to carbon. This feature allows carboranes to be integrated into virtually

any organic systems allowing the two chemistries to merge. Carboranes have a

nomenclature akin to their parent boranes. Consequently, several categories and sizes

coexist. In the present survey, only the dicarba-c/o5o-dodecaboranes (C2B10H12) will be

of interest and discussed. Therefore, any allusion to carboranes will be restricted to this

framework unless mentioned otherwise.

Among the 12-vertex carboranes, there are three types of isomers: ortho, o or 1,2;

meta, m. or 1,7; para, p or 1,12. All three present an icosohedral geometry that is shown

Figure 1.6. The synthesis of o-carborane (Figure 1.5), first reported in 1963 by two

groups, [29-32] results from the condensation of acetylene with decaborane in the

presence of ligands (generally acetonitrile, tertiary amine or thioether).[33-35]

2CH3CN + H = H ^ ^ ^ CH3CN + H2

oBH• CH

Figure 1.5 Synthesis of o-carborane by coupling of acetylene with decaborane

11

Figure 1.6 The three isomers: o-, m-, p-carboranes.

Functionalized acetylenes can be used during the synthesis so long as the groups

are not nucleophile. The m- and p-carborane are obtained successive high temperature

isomerizations whose mechanism was explored by Lipscomb and then refined by

Parisini. [36-39] These isomerizations occur under inert atmosphere between 400 and

500°C for the meta and 600-700°C for the para derivative (Figure 1.6). [40]

Even if chemists have crafted numerous ways to functionalize them, [4 1-54]

closo-carboranes display a relative chemical inertness in addition to a phenomenal

resistance to high temperatures. This sturdiness emerges from the nature of its core

component: boron. With more valence orbitals (3) than valence electrons (4), boron is

present in conventional 2e-2c bonds (e: electrons, c: centers) and non-classic 2e-3c

bonds.

In the latter systems, three atoms each provide one orbital to produce one bonding

and two non-bonding molecular orbitals. Only two electrons are therefore shared between

the three centers.[55-57] This particularity gives rise to the deltahedral (triangular)

geometry, characteristic of borane chemistry. This thought-provoking binding pattern

allows for the unique superaromaticity of carboranes. [58-60] that makes them the 3-D

equivalents of benzene. Their size (5.25A for the diameter of a carborane vs 4.72A for

benzene) and reactivity (electrophilic substitutions) are surprisingly similar. [61] As

12

illustrated by their electron withdrawing character (ortho » meta >para),[62] carboranes

have relatively low pKa at the C positions {pKa{ortho) = 22.0, pKa{mefa) = 25.6,

pKaipara) = 26.8)[59] that enable functionalization through deprotonation by organo

alkali reagents.

Figure 1.7 Size analogy between carboranes and phenyl rings (image from Ref. [25])

Their melting point ranges between 294-296°C for the ortho form. The meta form

is the intermediately thermally stable since its m.p. is around 272-273°C and the para

form, despite its being the thermodynamic isomer, has the lowest fusion temperature 259-

26rC.[63]

In order to understand how carboranes are going to behave in a polymeric matrix,

it is important to understand how carboranes assemble. Density is a property that reflects

this packing. The density of crystalline carborane is 0.999 g/cm at 25°C.[63] Like other

globular structures, carborane are classified as plastically crystalline. [64] This

denomination signifies that they are similar to crystals in the sense that their center of

mass organizes in a crystalline fashion. However, there is a temperature above which the

molecules can revolve about this barycenter, the glass transition temperature (by analogy

with plastics). Carlorimetric studies show that o-carborane undergoes a first order

transition at 273.6 K and a second order transition at 160 K. More importantly, o-

carborane presents a glass transition temperature situated at 120 K which underlines a

13

certain useful plasticity at low temperatures. These features will most definitely be useful

as we study the possible crystallization behavior of carborane in our polymers.

1.2.2 A Brief Overview of Possible Applications

Carboranes find applications in a multitude of fields. [25,65-66] For the sake of

brevity, the following is a non-exhaustive itemized list of applications. References are

provided should the reader desire to learn more about a particular item:

• Boron clusters in medicine

Boron clusters have been used in boron neutron capture therapy of cancer (see

Chapter 2). The following examples illustrate two of the many systems that have been

envisioned for the delivery of boron agents to tumor cells. [25]

X = NMe3.Se

Figure 1.8 Examples of carriers

• Metal ion extraction

The example below illustrate a possible utilization of cobalt dicarboUide for

nuclear waste treatment. The highly stable cobalt dicarbollide ion allows for the exchange

of sodium ions with radioactive cesium ions. This separation is of high importance in

14

terms of waste treatment. In a spent fuel rod used to power a nuclear plant, the waste is

chiefly composed of uranium and plutonium (over 95%) and the latter can be isolated

from the other radioactive elements, mostly '^^Cs and ^*^Sr, by acid treatment. However,

storage still represents an issue that has yet to be addressed. On the other hand having a

method that permits the recovery of cesium in a suitable form can serve in applications

such as medical supplies and food sterilization. [65]

Figure 1.9 Research towards ion exchange membranes radioactive

• Anti-crown reagent

Much like crown ethers are known for their ability to specifically separate cations.

Hawthorne et al. have developed a variety of mercury bridged compounds susceptible of

separating anions and particularly halogen atoms according to their size. [25,67]

15

Figure 1.10 Representations of unsubstituted [12]mercuracarborand-4 (left) and

[9]mercuracarborand-3 (right)

• "Almost" non coordinating ions[68]

Due to their extremes stability, carborane anions (here the monocarbaborane)

display amazing non coordinating properties that are particularly useful in the synthesis

of superacids and various organometallic architectures.

« f

Figure 1.11 Illustration of the non-coordinating properties of the monocarbaborane,

formation of a silver complex (image from Ref. [68])

• Homogeneous catalysis

A wide variety of catalysts have been developed using boron cluster chemistry

including rhodium, hafnium, titanium or zirconium catalysts for hydrogenation,

hydrosilation, hydroformylation and olefin polymerization. [25]

16

Figure 1.12 Hafnium catalyst for alkyne hydrogenation

• Liquid crystals and self assembly

Liquid crystalline materials have been developed using carboranes with the view

of diversifying the core molecules that chemists could use as well as benefiting from the

extreme stability of carboranes. Various studies have shown the utilization of boron

clusters for self-assembly processes. Whether it is through the particularities of the B-H

bonding or just using molecular interactions, carborane systems exhibit astounding self-

assembly properties that could, coupled with polymers, yield compelling

structures. [25,69-70]

17

• c

O BH

Figure 1.13 Liquid crystals and self-assembly. An example of possible liquid-

crystalline structure (top), clusters self-assembly (bottom, image from Ref. [69])

• Chains/Rings/Rods

A vast array of molecular rods, cycles and other morphologies have been

synthesized using the various possibilities offered by the different isomers (ortho, meta

and para). In addition, transmission electron microscopy studies of carboranes confined

inside the walls of carbon nanotubes have revealed an interesting staggered

morphology . [25,7 1]

18

Figure 1.14 Cycles and rods. Macrocycles containing carboranes (top). B)

Illustration of the staggered morphology observed by transmission electron

microscopy (bottom, image from Ref. [71])

1.2.3 A Review of Previous Literature on Carborane Polymers.

Due to their very good thermal stability, carboranes have been mostly used to

enhance thermomechanical behaviors of polymers. Though they have been incorporated

as plain fillers, most of the attention revolves around their utilization in applications

where they are covalently bound to a monomeric unit either in the backbone or as a side-

group. [52,65,66,73-86] Consequently, the present survey will only include examples of

main-chain and pendant group carborane polymers.

Examples of carborane polymers and their formulae are shown below (Figure

1.14 and 1.15). They are classified according to the position of the carborane (backbone

or side-group). We acknowledge that this list is far from being complete, but it illustrates

the most relevant polymers in respect to this work.

19

Figure 1.15 Examples of polymers with carboranes in the backbone

Main-chain carborane polymers have drawn the attention of polymer scientists

due to initial results showing that thermal resistance was somewhat greater than their

side-chain counterparts. As a consequence, they represent the greater part of the work in

this field. However, with this route, one has to resign to using step-growth polymerization

techniques. The latter does not offer as much control of architectures as chain

polymerization. In actuality, both methods can and have been employed for pendant-

carborane polymers. In our search for tailored architectures, we will mostly focus on

chain polymerization techniques except in Chapter 4.

20

Figure 1.16 Examples of polymers containing carboranes as pendant groups.

At the time when this study begun, there had been only two reports of well-

defined macromolecular architectures incorporating carboranes in the literature. Adronov

et al. had reported their incorporation in dendritic structures as well as the polymerization

of an acrylate carborane monomer by atom-transfer radical polymerization

(ATRP). [52,87] This work is also pivotal in that it is one of the first examples of the

utilization of carboranes for properties other than mere thermomechanical reinforcement.

Unpublished work from the doctoral thesis by Man had also emphasized the versatility of

carborane-based polymers, by using them as ion exchange membranes. [65] During the

course of this work, the number of studies dealing with the incorporation of carboranes in

controlled architectures for advanced applications has increased dramatically. These

recent advances will be discussed in the following chapters, alongside the findings of the

present work.

21

Figure 1.17 Reported examples of quasi-living polymerizations for the design of

macromolecular architectures embedding boron clusters by ATRP.

1.3 Outline of the Dissertation

In this introductory chapter, we have reviewed the basic philosophy of hybrid

polymers and particularly, the incorporation of inorganic structures in polymeric

materials, and we have discussed carborane chemistry from its core component to its

applications and incorporation in macromolecules. Based on this knowledge, this thesis

will focus on the incorporation of carborane clusters so as to obtain carborane-based

functional polymeric architectures. In chapter 2, the possibility to design novel

amphiphilic diblock copolymers containing carboranes via ring-opening metathesis

polymerization is explored. There, the synthesis and polymerization of a novel

oxanorbornene is described as well as some data about solution behavior and cytotoxicity

of the polymer. Chapter 3 reports the copolymerization of that oxanorbornene polymer

with cyclooctene and dicusses some of the structural and morphological properties of the

obtained polymers. Dibromofluorenes with pendant silylcarborane moieties are

synthesized in chapter 4. Their homo- and copolymerization with dihexylfluorene using

nickel-mediated polymerization is investigated. Chapter 5 highlights the possibility to

utilize well-defined boron clusters for applications in lithographic applications.

Particularly, their utilization in nanoimprint lithography is depicted. Finally, chapter 6

22

illustrates potential research avenues based on some of the preliminary findings of this

work.

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[79] D. A. Brown, H. M. Colquhoun, J. A. Daniels, J. A. H. Macbride, I. R.

Stephenson, K. Wade, Journal ofMaterials Chemistry 1992, 2, 793.

[80] S. Packirisamy, D. Schwam, M. H. Litt, Journal of Materials Science 1995, 30,

308.

[81] H. M. Colquhoun, P. L. Herbertson, K. Wade, I. Baxter, D. J. Williams,

Macromolecules 1998, 31, 1694.

[82] M. A. Fox, K. Wade, Journal ofMaterials Chemistry 2002, 12, 1301.

[83] R. Ma, Y. Bando, Chemical Physics Letters 2002, 364, 314.

[84] M. K. Kolel-Veetil, H. W. Beckham, T. M. Keller, Chemistry ofMaterials 2004,

76,3162.

[85] M. Patel, A. Swain, J. L. Cunningham, J. J. Murphy, R. S. Maxwell, S. C. Chinn,

Abstracts of Papers, 230th ACS National Meeting, Washington, DC, United

States, Aug. 28-Sept. 1, 2005 2005, MSE.

[86] D. T. Welna, J. D. Bender, X. Wei, L. G. Sneddon, H. R. Allcock, Advanced

Materials (Weinheim, Germany) 2005, 17, 859.

[87] M. C. Parrott, E. B. Marchington, J. F. Valliant, A. Adronov, Journal of the

American Chemical Society 2005, 727, 12081.

27

CHAPTER 2

AMPHIPHILIC BLOCK COPOLYMERS FOR BORON NEUTRON CAPTURE

THERAPY

2.1 Introduction

As pointed out in the previous chapter, there has been a growing interest in

incorporating carboranes into tailored macromolecular structures by means of Hving or

quasi-Hving polymerizations. [1-3] This regain of interest stems from the rising awareness

that carborane-based macromolecules can span a gamut of applications, for example:

non-linear optical materials, [4-9] precursors for ceramics,[10-13] boron neutron capture

therapy of cancer (BNCT),[14,15] etc. The work reported in this chapter is particularly

relevant to the latter application and a brief explanation of the principles governing

BNCT and some basics about polymer drug delivery can be found in Appendix A.

Adronov was the first to report the direct incorporation of carborane moieties in well-

defined macromolecules (PDI < 1.2) by controlled radical polymerization, and by

sequential dendrimer synthesis. [2, 16- 18] In their controlled radical experiment, they have

demonstrated the possibility of incorporating carboranes in polymers of narrow

polydispersity. However, loss of control upon attempted formation of the second block

hampered the formation of well-defined amphiphilic structures. [2, 16] Seminal work by

Sneddon and coworkers on precursors for boron-containing ceramics have highlighted

the use of ring-opening metathesis polymerization (ROMP) to obtain high-boron content

polymers that can undergo pyrolysis to form a boron carbide/carbon network. [1,1 9-22]

Building upon this work, Malenfant et al. have recently shown how ROMP can be used

28

for the synthesis of boron-containing diblock copolymers and their subsequent

transformation into nano-ordered ceramics. [3]

In the following chapter, the synthesis of a boron-containing monomer based on

an oxonorbomene functionalized o-carborane and its subsequent ring-opening metathesis

polymerization to obtain low-polydispersity (PDI < 1.1) high-molecular weight

carborane-based polymers is described. The formation of amphiphilic block copolymers

is demonstrated via sequential monomer addition, followed by deprotection of the second

block to generate the amphiphilic copolymers. Initial solution behavior studies by

dynamic light scattering (DLS) and atomic force microscopy (AFM) are also discussed.

Once the diblock was characterized, post-polymerization modifications on the pendant

amine are explored and subsequent cell studies are reported. Additionally, an alternative

route using norbornene esters with polyethylene glycol (PEG) chains is also investigated.

These copolymers are unique examples of a narrow polydispersity amphiphilic

architectures incorporating carboranes that paves the way for the exploration of potential

applications ranging from nanoscopic templates in thin film applications, [23] to boron

neutron capture therapy for the treatment of cancer. [14,24]

2.2 Route A: Polymerization Using a Protected Amine, Deprotection and

Subsequent Functionalizations

2.2.1 Experimental Section

2.2.1.1 Materials.

All organic reactants and reagents were purchased from Aldrich Chemical Co.

and used as received unless specified otherwise. Anhydrous benzene and diethyl ether

29

were dried over sodium with benzophenone as an indicator. Dichloromethane (DCM)

was obtained through Fisher, distilled over calcium hydride and degassed with freeze-

pump-thaw cycles. 0-carborane was supplied by KatChem.[25] Grubbs' third generation

catalyst was synthesized according to the literature procedure and stored under nitrogen

atmosphere. [26]

2.2.1.2 Instrumentation.

Gel permeation chromatography (GPC) measurements for the homopolymers 4

were performed in tetrahydrofuran (THF) at 1.0 mL/min using a Knauer K-501 Pump

with a K-2301 refractive index detector and a K-2600 UV detector, and a column bank

consisting of two Polymer Labs PLGel Mixed D columns at 40°C. All other

measurements were performed using a similar system with a column banks consisiting of

three Polymer Labs PLGel Mixed D columns at 40°C. Molecular weights are reported

relative to polystyrene standards.

NMR, "B NMR and '^C NMR were recorded at 300 MHz, 128 MHz and 100

MHz respectively on a Bruker NMR spectrometer at room temperature in deuterated

chloroform. The individual NMR spectral assignments do not list the carborane B-H

resonances. Due to the quadrupolar nature of boron, the resonances for the 10 B-H are

observed as broad multiplets (6 (ppm) = 3.20-1.01). The integration of these multiplets

accounts for 10 H. Melting points were measured with a melting point apparatus

Electrochemical Mel-Temp in a capillary tube.

Dynamic Light Scattering (DLS) was performed in 1 8 mQ water. The sample was

prepared as followed; 30 mg of deprotected polymer were first dissolved in dimethyl

30

sulfoxide DMSO (30mL). To this solution, 30 mL of 18 mQ water were added using a

syringe pump at a rate of 1 5 mL/h. The solution was then transferred into a dialysis bag

and dialyzed against 2 L of 18 mQ. water for 2 days, renewing the water three times along

the process. All experiments were performed at room temperature using an ALV unit

equipped with an ALV/SP-125 precision goniometer (ALV-Laser Vertriebsgessellschaft

m.b.h.), an Innova 70 argon laser (Xq = 514.5 nm, max. power 3 W. Coherent Inc.)

operated at 300 mW, and a photomultiplier detector (Thorn EMI Electron Tubes). Signal

from the detector was processed by an ALV 5000 Multiple Tau Digital Correlator board

and associated software. The solutions were prefiltered through PVDF filters of 0.25-mm

pore size. The experiment was performed using a polymer (PDI = 1.10, Mn = 30.500

g/mol with complete deprotection as monitored by 'H NMR, molar ratio

(S0NlC/B0NlA)-2/l).

The investigation of the shape and topography of the micelles was performed

using Atomic forceMicroscopy (Digital Instrument, Dimension TM 3100) using

Nanoscope ® Ilia, version5.12r3 software, in tapping mode.

For the cell studies, monolayers of HEp-2 human laryngeal carcinoma cells were

grown to approximately 80% confluency in 10% fetal bovine serum (FBS, Atlanta,

Biologicals, Lawrenceville, GA) and imemzo (Richter's improved MEM insulin, Irvino

Scientific, Santa, Ana CA). The media was then removed and 195 |j.L of the dialyzed

solution of polymer was added to 250 \xL 10% FBS/Cyclohexamide (Cyclohexamide

overlay medium base, Cambrex, Walkersville, MD) and put on cells. [27] The cells were

incubated for about 22 h and were then washed three times with sterile phosphate buffer

31

solution. The washed cells were then mounted with DAPI mounting medium. The

viability of the cells was measured using a Trypan blue exclusion test.

2.2.1.3 Synthesis and Spectral Data

Preparation of the l-(tert-butyl-dimethylsilanyl)-l,2-dicarba-closo-

dodecaborane(12) 2. Compound 2 was prepared using a slight modification of a

Hawthorne procedure. [28] In a round-bottom 500 mL Schlenk flask capped with a rubber

septum and equipped with a magnetic stir bar. Under a nitrogen atmosphere, sublimed o-

carborane 1 (15 g, 104 mmol, 1 eq) in a 2:1 mixture of benzene/ether (40 mL/20 mL)

was deprotonated using n-butyl-lithium (78 mL, nBuLi 1.6 M, 125 mmol, 1.2 eq) at 0 °C

dropwise. After 45 min, t-butyldimethylsilyl (TBDMS) chloride (TBDMS-Cl, 20.4 g,

135 mmol, 1.3 eq) in 30 mL of a benzene/ether (2:1 V:V) solution was added. After the

addition of the silyl compound, the stopcock was closed and the septum removed. A

rubber septum-capped condenser was fitted on top of the reaction flask with a nitrogen

overpressure. The stopcock was then opened and the solution was brought to reflux. After

refluxing overnight, the solution was quenched with a few drops of methanol to prevent

exothermic reaction upon addition of 40 mL of water. The layers were separated in a

separatory funnel and the aqueous solution was extracted with additional Et20 (2 x 40

mL). The combined extracts were dried over MgS04 and concentrated in vacuo to give a

slightly yellowish solid that was then distilled (85 °C, 20 mTorrs) to yield 24.7 g of a

white powder, silyl-o-carborane 2 (92% yield). Also, there was no trace of remaining o-

carborane. To verify the absence of any starting material in the final product, a careful

sweep of temperatures, from 20°C up to 85 °C, at constant pressure (10 mTorrs) was

32

performed with no apparent condensation of any solid prior to the final temperature.

Conversely, keeping a constant temperature (85 °C) and carefully decreasing the pressure

in the system, from 1 atm down to 10 mTorrs, no remaining o-carborane condensation

was noted. High Resolution MS (EI+): m/z calcd 258.2758, found 258.4915; 'H NMR

(CDCI3): 6 (ppm) = 3.46 (s, IH, CH), 1.03 (s, 9H, CCH3), 0.26 (s, 6H, SiCHs); '^C NMR

(CDCI3): 5 (ppm) = 66.02, 60.25, 26.98, 19.32, -4.56 ; "B {'H} NMR (CDCI3): 6 (ppm)

= 0.28 (IB), -1.80 (IB), -7.03 (2B), -10.75 (2B), -13.28 (2B); mp = 61°C.

Preparation of the [2-(tert-butyl-dimethyl-silanyl)-l,2-dicarba-closo-

dodecaboran(12)-l-yl]-propan-l-ol 3. Compound 3 was prepared using a slight

modification of a Hawthorne procedure in a setup comparable to the one used for 2. [28]

Under a nitrogen atmosphere, compound 1 (15 g, 58 mmol, 1 eq) in benzene/ether (2:1

V:V) was deprotonated using dropwise addition of nBuLi (43.5 mL of a 1.6 M solution,

69.6 mmol, 1.2 eq) at 0°C. Trimethylene oxide (4.9 mL, 75.4 mmol, 1.3 eq) was added

after 45 min and the solution turned light yellow. The solution was refluxed overnight

and turned orange. The reaction was quenched with a few drops of methanol and 40 mL

of water. The layers were separated in a separatory funnel and the aqueous solution was

extracted with additional Et20 (2 x 40 mL). The combined extracts were dried over

MgS04 and concentrated in vacuo to give a sticky solid. The paste was then

recrystallized from boiling hexanes followed by cooling at -4 °C. The thin fibrous white

crystals were then filtered over sintered glass to obtain 15.6 g of carboranylpropanol 3

(85% yield). High Resolution MS (EI+): m/z calcd 315.3160, found 315.3155; 'H NMR

(CDCI3): 5 (ppm) = 3.69 (q, 2H, C//2OH), 2.34 (qu, 2H, C//2CH2OH), 1.78 (t, 2H, CH2-

Cage), 1.06 (s, 9H, CCH3), 0.31 (s, 6H, SiCH3); ); ^^C NMR (CDCI3): 5 (ppm) == 81.28,

33

76.47, 61.55, 35.51, 34.68, 27.80, 20.35, -2.48; "B {'H} NMR (CDCI3): 6 (ppm) = 0.21

(IB), -3.95 (IB), -7.33 (2B), -10.31 (6B); mp = 83°C.

Preparation of (lR,2R,6S,7S)-4-{3-[2-(tert-Butyl-dimethylsilanyl)-l,2-clicarba-

closo-dodecaboran( 1 2)- 1 -yl]propy 1 } - 1 0-oxa-4-aza-tricyclo[5.2.1.0^-^]dec-8-ene-3,5-dione

referred to as Silyl-protected OxoNorbornene Imide Carborane (SONIC) 4. In a dry 500

mL flask, exo-7-oxonorbomene imide (7.6 g, 46 mmol, 1 eq), [2-(tert-butyl-dimethyl-

silanyl)-l,2-dicarba-closo-dodecaboran(12)-l-yl]-propan-l-ol 3 (16 g, 51 mmol. 1.1 eq)

and triphenylphosphine (13.3 g, 51 mmol, 1.1 eq) were dissolved upon stirring in 300 mL

of freshly distilled dry tetrahydrofuran (THF). The flask was kept under nitrogen pressure

and cooled down to 0°C with an ice bath. After 5 minutes, diisopropylazodicarboxylate

(DIAD) (3.2 mL, 16.26 mmol, 1.1 eq) was added and the solution turned yellow. The

reaction was allowed to react overnight (16 h) affording a deep-yellow solution. The

crude mixture was then concentrated in vacuo to obtain a sticky yellow paste. The paste

was then redissolved in minimum amount of THF and precipitated by dropwise addition

into hexanes (800 mL). The precipitate was a white powder with a slight reddish tint. The

powder was then redissolved and precipitated a second time. The precipitate was then

recrystallized from boiling methanol followed by cooling at -4°C, affording 18.6 g of flat

square white crystals (87% yield). High Resolution MS (FAB-): m/z calcd 463.3505,

found 463.3560; 'H NMR (CDCI3): 6 (ppm) = 6.52 (s, 2H, CH=CH), 5.24 (s, 2H,

bridgeheads), 3.46 (t, 2H, NCH2), 2.85 (s, 2H, NC(O)CH), 2.09 (m, 2H, NCH2CH2), 1.82

(m, 2H, NCH2CH2CH2), 1.06 (s, 9H, CCH3) 0.32 (s, 6H, SiCHs); '^C NMR (CDCI3): 5

(ppm) = 176.13, 136.53, 80.96, 80.37, 75.92, 47.43, 37.97, 34.98, 28.31, 27.51, 20.39, -

34

2.60; "B {'H} NMR (CDCI3): 5 (ppm) = 0.31 (IB), -3.85 (IB), -7.49 (2B), -10.25 (6B);

mp= 136°C.

.Si

a) nBuLi, 0"C

b) TBDMS-CI, 40°C

c) MeOH/H20

Benzene/Et20

Benzene/

Et20

oMitsunobu Coupling

THF, DIAD, PPh3

a) nBuLi, 0"C

b) Oxetane, 40°C

c) MeOH/H20

4 3

Figure 2.1 Synthesis of the SONIC monomer 3. TBDMS: /^rbutyldimethylsilyl.

DIAD: diisopropylazodicarboxylate.

Homopolymerization of SONIC 5. The procedure was the same for every

homopolymerization. Here is a standard procedure for the reactions carried out in septum

vials, under constant agitation and under nitrogen atmosphere. To a 1 mL of solution of

the desired amount of GUI, 200 mg of monomer 4 (4.31mmol) in 10 mL of

dichloromethane were introduced rapidly and stirred for 6 minutes. After that time, the

reaction was quenched with an excess of ethylvinylether and precipitated dropwise in

cold methanol (150 mL) to afford a white powder. Table 1.1 shows the resuhs obtained

for different monomer to catalyst ratios. 'H NMR (CDCI3): 6 (ppm) = 6.09 (br s, 0.84H,

olefin trans), 5.82 (br s, 1.1 6H, olefin cis), 5.02 (br t, 1.16, CHO, cis), 4.46 (br s, 0.84H,

CHO, trans), 3.6-3.2 (m, 4H, N-CH2, CH-C(O)), 3.0-1.3 (br, 14H, BH, CH2CH2), 1.08 (s.

35

9H, CCH3), 0.34 (s, 6H, SiCHs); '^C NMR (CDCI3): 5 (ppm) = 175.31, 131.10, 80.96,

80.18, 76.24, 52.37, 38.07, 35.13, 28.46, 27.54, 20.40, -2.47.

Diblock copolymer synthesis 6. In a screw cap vial under nitrogen atmosphere and

constant agitation, the desired amount of SONIC was dissolved in 5mL of DCM and the

catalyst was introduced as a 10 mM solution in DCM. After 5 min. {2-[(lR,2R,6S,7S)-

3,5-Dioxo-10-oxa-4-aza-tricyclo[5.2.1.02,6]dec-8-en-4-yl]-ethyl}-carbamic acid tert-

butyl ester referred to as Boc-protected OxoNorbomene Imide Amine (BONIA),[29]

dissolved in 5 mL of DCM, was introduced into the reaction media using a syringe. The

reaction was quenched after lOmin by addition of excess ethyl vinylether. The solution

was then precipitated into 50 mL of hexanes and filtered over sintered glass as a white

solid.

Deprotection; Synthesis of an amphiphilic diblock copolymer 7. In a 35 mL

round-bottom flask, the polymer (150 mg) was dissolved in 4 mL of DCM and 15 mL of

trifluoroacetic acid and allowed to react overnight. The polymer salt was then

precipitated in diethyl ether and filtered over sintered glass.

36

c) <^0^6 7

Figure 2.2 Ring-opening metathesis polymerization and subsequent amine

deprotection syntheses. TBDMS: /^r/-Butyldimethylsilyl, TFA: Trifluoroacetic acid.

Post-polymerization PEGylation 8a. In a 50 mL round-bottom flask, polymer 7 (1

equiv.) was dissolved in dimethylsulfoxide (20 mL). Triethylamine (2 equiv.) were added

and the reaction was allowed to stir for 20 min. PEG-acrylate (10 equiv.) was then added

to the mixture and the mixture was allowed to react for 2 days. To obtain 8b, the same

procedure was utilized except that the reaction temperature was increased to 60 °C and

some of the polymer solution was dialyzed against THF after reaction. In both cases, the

yields were extremely low (below 10%) and just enough was recovered for 'H NMR.

Attachment ofRhodamine-B 9. In a 25 mL round-bottom flask, polymer 7 (Ig, 1

equiv.) was dissolved in DMSO (15 mL) and rhodamine B isothiocyanate (40 mg, 0.1

equiv.) was added to the mixture. A drop of triethylamine was then added and the

mixture was allowed to react in the dark for 1 day. The mixture was then precipitated in

cold diethyl ether to yield 850 mg of a pink powder (Yield 85%).

37

X"

Figure 2.3 Post-polymerization modifications

2.2.2 Results and Discussion

Gomez et al. had previously reported a protocol to synthesize the 3-[2-(ferNbutyl-

dimethylsilanyl)-l,2-dicarba-c/o50-dodecaboran(12)-yl)propan-l-ol 3 (Figure 2.1). [28]

The synthesis of this entity was key to the elaboration of the targeted monomer 4.

However, while reproducing their experiments, slight modifications were introduced. The

distillation of o-(C2BioHii)SiMe2/Bu 2 occurred at higher pressure and lower

temperatures than previously reported.

The oxanorbomene derivative 4 was synthesized via Mitsunobu coupling of exo-

7-oxonorbomene imide and 3. [30,31] A previous study in our group had demonstrated

the difference in polymerization rates between exo and endo carborane-containing

38

norbomene derivatives, [3 2] corroborating findings by Grubbs and coworkers. [3 3] In

order to maximize the polymerization rates, an isomerically pure exo compound was

needed. Furthermore, to avoid the problems of head-to head and head-to-tail additions, a

symmetric monomer was desirable. To address these issues, we undertook the synthesis

of SONIC (Silyl-protected OxaNorbomene Imide Carborane), whose symmetry and

stereochemistry were specifically designed for faster and more controlled polymerization

kinetics. This control permits the exploration of well-defined architectures, such as

blocky structures.

Table 2.1Tabulated data for the homopolymerization of SONIC

Target

DPn

TargetPDf Yield

5i 54 25,000 22,000 1.07 83%5ii 108 50,000 58,600 1.09 82%5iii 162 75,000 79,100 1.05 87%5iv 216 100,000 97,600 1.03 89%

^ g.mor'. As measured by GPC vs polystyrene standards.

The homopolymerization of SONIC afforded polySONIC 5 in good yields (>

82%)) and very narrow polydispersity (PDI < 1.1). To achieve this task, advantage was

taken of the versatility and efficacy of ROMP catalysts, that not only give a living

character to the polymerization, but also display a greater tolerance to diverse chemical

functionalities. [26] The reaction happens indeed within minutes and offers good control

over molecular weight and molecular weight distribution, with no apparent broadening

even for the highest Mn.

39

Table 2.2 Tabulated data for the copolymerization of SONIC 4 and BONIA by

ROMP.

EntryMolar Ratios

SONIC BONIADPn(S) DPn(B)

Target

6i 4 5 22 28 18,835 17,300

6ii 2 1 50 25 30,894 32,990

6iii 8 5 54 34 35,523 33,800

6iv 4 5 54 68 46,006 45,500

6v 4 5 86 108 73,178 65,100

PDl"

g.mol"'. As measured by GPC vs polystyrene standards.

The diblock copolymers were obtained by sequential addition of SONIC and

BONIA (Boc-protected OxoNorbomene Imide Amine) (Figure 2.2). These copolymers

were obtained in good yields (> 80%) and with molecular weights ranging from 17 to 65

kg/mol. Also, the favorable comparison, between estimated and measured molecular

weights, suggests that the polymers obtained behave like random coils in tetrahydrofuran.

Even at high molecular weights, the polydispersity remains very narrow (Figure 2.4;

Table 2.2, Entry 6v). The gel permeation chromatogram illustrates the increase in

molecular weight upon addition of the second block (Figure 2.4). In addition, the molar

feed and incorporation ratios are within 5% of one another as determined by 'H-NMR

spectroscopy.

40

18 20 22

ButionTinrBfmn'i

Figure 2.4 GPC chromatograms in THF of poly(SONIC) (solid line, PDI = 1.08, M„= 37 kg/mol) and poly(SONIC-A-BONIA) (dashed line. Entry 6v, PDI = 1.11 M„ = 65

kg/mol).

Homopolymers of BONIA had previously been reported by our group as potential

antibacterial polymers. [29] Their low toxicity to red blood cells opens the prospects of

medical applications for the synthesized diblock copolymers. The amphiphilicity,

necessary for the formation of micelles that can be used as boron neutron capture therapy

agents, [14] was achieved through a post polymerization cleavage of the ?Boc protecting

group in the second block. In so doing, the copolymers obtained are a unique example of

a well-defined (PDI < 1.15) amphiphilic copolymer containing carborane. The

deprotection can be monitored by the disappearance of the characteristic N-H carbamate

peak at 6 = 6.89 ppm integrating for IH and the disappearance of the 9H from the tert-

butyl protons at 5 = 1.35 ppm. At the same time, the appearance of the ammonium peak

41

at 5 = 8.01 ppm integrating for 3H is observed. As observed by 'H NMR spectroscopy,

the cleavage is quantitative.

50 0.0

ppm(fl)

Figure 2.5 Illustration of the appearance of the ammonium peak at 8 ppm.

In addition, solution studies in water, using DLS, show the propensity of these

polymers to aggregate. This phenomenon can be imputed to the formation of micelles

were the charged hydrophilic block constitute the corona and the carborane containing

block the core. These aggregates have an average hydrodynamic radius (Rh) of 41rmi

(Figure 2.6).

42

Atomic force microscopy was utilized to confirm the presence of aggregates and

evaluate their shape. Figure 2.6 shows the presence of circular objects on a silica surface.

These objects are found to have a radius of approximately 87 nm. This number is much

larger than the hydrodynamic radius found in solution by DLS. However, the micelles are

expected to flatten out as the positively charged ammoniums interact with the negatively

charged silanols of the silica surface, leading to an apparent increase in size. This

interaction is confirmed when looking at the profile of these cylindrical objects, as they

are measured to be only 10 nm tall. A back of the envelope calculation allows us to

calculate both the volume of a sphere with a 40 nm radius and a 1 0 nm-tall cylinder with

a radius of 90 nm to be approximately 250 nm . Therefore, there seems to be a

conservation of volume and these results lead us to believe that the value obtained by

DLS is probably more accurate. Nevertheless, AFM provides some valuable insight into

the shape of the micellar objects. Additionaly, the size might appear bigger because of the

finite curvature of the AFM tip.

Figure 2.6 Distribution of sizes measured by dynamic light scattering (left) and

atomic force microscope image (right) of micellar aggregates (Entry 6v).

43

8 0 7 0 6.0 5 0 4 0 3 0 2 0 1 0

ppm (f1)

Figure 2.7 'H NMR experiment illustrating the solvents of different polarities

As illustrated by Figure 2.3, the deprotected amine provides us with a number of

different post-polymerization possibilities. In particular, the PEGylation of the amine via

a Michael addition of PEG-acrylate has been investigated at different temperatures. In

both cases, the disappearance of the ammonium peak at 5 = 8.0 ppm was observed as

well as the appearance of the characteristic PEG signal at 3.5 ppm. The synthesis of 8b

was attempted as a way to accelerate the kinetics of the reaction by increasing the

reaction temperature. However, after taking an aliquot after 1 day, it was observed that

the signals corresponding to the silyl group at 5 = 1.06 and 0.33 ppm had disappeared,

while a new signal at 5.1 ppm had appeared (Figure 2.5). The latter signal is the

characteristic resonance of the C-H bond of carborane. Although the mechanism still

44

remains unclear, it seems that the presence of triethylamine at high temperature is directly

correlated with cleavage of the TBDMS group. A similar observation has been made

when trying to hydrogenate polymer 5 in the presence of tri-«-propylamine, as will be

discussed in chapter 3.

The introduction of PEG side chains is particularly important for the utilization of

polymers in intravenous systemic delivery. Firstly, the PEG chains act as a hydrated

cushion that prevents the adhesion of opsonizing proteins. [34] By making the polymer

"stealthy" to the immune system, the PEG chains increase the blood circulation half-time

of the polymer which results in better accumulation at the desired location. [35] Secondly,

the bottle-brush architecture is believed to limit renal excretion by hampering the

reptation of the macromolecules in the kidney. [36] Again, this phenomenon also prolongs

the circulation of the drug, rendering it more efficacious.

For topical applications, the presence of PEG chains is not quite as relevant as the

risks of opsonization are greatly reduced. Therefore, it is very interesting to study the

interaction of the charged polymer with carcinoma cells. In order to study this interplay

in vitro, the attachment of a rhodamine B isocyanate was also undertaken (Figure 2.3).

The yields were increased in comparison to those of the PEGylation reaction, as the

solubility of the PEG groups complicates the precipitation step. Nevertheless, it was still

difficult to quantify the level of attachment. In particular, the ionic nature of the polymer

was a limiting factor for its injection in a GPC apparatus, to monitor the dye attachment

to the polymer by UV detection. During the dialysis process of polymer 9 against water,

a light pink coloration appeared outside of the dialysis bag. This phenomenon indicates

that there is still some unattached dye that was not removed by the precipitation in diethyl

45

ether. However, the coloration gradually faded upon continuous changing of the dialysis

water. After 3 days, virtually no color change was observed. The presence of a dark pink

color inside the bag suggests that the majority of the water-soluble dye had, in fact,

coupled with the amine. The polymer was dialyzed for another 2.5 weeks to ensure that

no residual dye would be present.

Confocal microscopy was utilized to evaluate the use of polymer 9 as potential

agent for BNCT. Figure 2.8 illustrates the results obtained upon incubation of HEp-2

carcinoma cells with a solution of dialyzed polymer. Three very important observations

have to be made. First of all, the internalization of labeled polymer 9 is apparent as

illustrated by the z-sections taken on the cells. Secondly, the majority of the internalized

polymer appears to be preferentially located around the nucleus of the cells. This

observation is important as it has been cited that BNCT is more efficient when the

delivery agent releases its cytotoxic payload closer to the nucleus of the cancerous cell.

Finally, it is important to remark that without the presence of any neutron source,

polymer 9 showed no cytotoxic effect after 22 h of incubation on cells in culture. The

viability of cells was determined by a Trypan blue exclusion test. The principle of this

test is that live, hardy cells possess an undamaged cell membrane that will exclude

certain dyes such as Trypan blue. Upon adding the dye, the number of cells in the

microscope field that had internalized the dye was comparable between the experimental

and control groups (~ 3 to 5%).

46

Figure 2.8 Confocal microscopy image of HEp-2 carcinoma cells after a 22h

incubation period.

While the synthesis of 8a, 8b and 9 showed the versatiHty of the chemistry that

can be performed on the deprotected amine, it proved difficuk to characterize the

compounds. Therefore, the very nature of these post-polymerization routes complicates

their implementation on a larger scale. Consequently, a possible alternative to the

synthetic routes described in part 2.2 was investigated using a PEG-norbornene ester.

2.3 Route B: Using PEGylated Norbornene Esters

2.3.1 Experimental Section

The PEG-functionalized norbornene, the NHS-norbomene ester and the tBoc-

protected dye were kindly provided by Dr. Alfred Sterling and Dr. Ahmad Madkour. Gel

permeation chromatography was performed with RI and UV detection with an excitation

at 460 nm.

Synthesis of triblock copolymers 10. In a 20 mL screw-cap vial, compound 4 (200

mg, 0.428 mmol) was dissolved in DMF (3 mL) and a 1 mL solution containing 10 mg of

47

Grubbs third generation catalyst (0.011 mmol) was added. After 5 min, the PEG

norbomene ester (200 mg, 0.167 mmol) in 3 mL of DMF was added and the mixture was

allowed to react for 30 min. The NHS activated norbomene ester (6 mg, 0.22 rrmiol) was

then introduced and the reaction was quenched after 3 min by addition of an excess of

ethyl vinyl ether.The polymer was then precipitated in cold diethyl ether (cooled with

liquid nitrogen) and filtered to yield 357 mg of a grey powder (88%).

Labelling of the triblock copolymer 11. In a 25 mL round-bottom flask, tBoc-

protected nitrobenzoxydiaxole (NBD) (13 mg, 4 equiv.) was dissolved in THF (8 mL)

and TFA was added (5 mL). After 4 h, the reaction mixture was syringed into another

round-bottom flask containing polymer 10(100 mg, 1 equiv.) in 10 mL of dry DMF. The

reaction was allowed to stir overnight.

48

N02

Figure 2.9Triblock copolymer formation and labeling.

2.3.2 Results and Discussion

The alternative route described here presents the advantage of circumventing the

post-polymerization PEGylation used in Route A by utilizing a PEG-functionalized

monomer. While no solution studies have been performed on these materials, they are

expected to lead to the formation of micellar assemblies comparable to that of Route A.

The triblock copolymers were obtained by sequential additions of the monomers (Figure

2.9). The control obtained for the obtained polymer is remarkable as the PDIs are below

1.15. The number average molecular weight (22,500 g/mol) is however much inferior to

the expected molecular weight (36,100 g/mol). This discrepancy can be accounted for by

49

the fact that comb architecture display a lower apparent molecular weight by GPC.[37]

The attachment of the dye was monitored by GPC using UV detection. The GPC

chromatograms (Figure 2.10) clearly show the detection of a refractive index change

upon elution of the unlabeled polymer 10 and the NBD-labeled polymer 11. However, by

UV detection, the unlabelled polymer is not detected which indicates the attachment of

the dye onto the polymer.

14 16 18 20 22 24 26 14 16 18 20 22 24 26

Figure 2.10 RI (left) and UV (right) GPC chromatograms of 10 and 11.

2.4 Conclusions

We have successfully developed a new monomer, SONIC, that enabled us to

synthesize amphiphilic diblock copolymers containing carborane with low PDI (< 1.15)

by two methods. The newly synthesized monomer was homopolymerized using ROMP

yielding materials with low PDI (< 1.1). The solution behavior of the copolymers

obtained by the polymerization-deprotection strategy (Route A) was characterized by

DLS and AFM. It was shown that spherical micelles can be obtained. Post-

Elution Time (min) Elution Time (min)

50

polymerization modifications were successfially undertaken to attach PEG-acrylate via

Michael addition and Rhodamine B isothiocyanate by nucleophilic substitituion.

Additionally, preliminary cell studies showed the incorporation of the labeled-polymers

inside carcinoma cells by confocal microscopy. An alternate method (Route B) was also

investigated where the carborane-containing oxanorbomene was polymerized with a

PEG-functionalized norbomene and an NHS activated norbomene ester. The NHS group

allowed for facile labeling of the triblock copolymer as monitored by GPC. The obtained

polymers by both routes are expected to provide a solid base for further exploration of

amphiphilic carborane-based copolymers in BNCT applications.

2.5 References

[1] X. L. Wei, P. J. Carroll, L. G. Sneddon, Chemistry ofMaterials 2006, 75, 1 113.


Symposia 2003, 196, 201.

[3] P. R. L. Malenfant, J. Wan, S. T. Taylor, M. Manoharan, Nature Nanotechnology

2007, 2, 43.

[4] N. Tsuboya, M. Lamrani, R. Hamasaki, M. Ito, M. Mitsuishi, T. Miyashita, Y.

Yamamoto, Journal ofMaterials Chemistry 2002, 72, 2701

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[5] J. Taylor, J. Caruso, A. Newlon, U. Englich, K. Ruhlandt-Senge, J. T. Spencer,

Inorganic Chemistry 2001, -/O, 3381

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[6] R. Hamasaki, M. Ito, M. Lamrani, M. Mitsuishi, T. Miyashita, Y. Yamamoto,

Journal ofMaterials Chemistry 2003, 7i, 21.

[7] C. D. Entwistle, T. B. Marder, Angewandte Chemie, International Edition in

English 2002, 41, 2927.

[8] D. G. AUis, J. T. Spencer, Inorganic Chemistry 2001, 40, 3373.

[9] D. G. Allis, J. T. Spencer, Journal ofOrganometallic Chemistry 2000, 614, 309.

[10] R. K. Zalavutdinov, A. E. Gorodetsky, A. P. Zakharov. Mikrochimica Acta 1994,

77-7-775, 533.

51

[11] V. L. Solozhenko, N. A. Dubrovinskaia, L. S. Dubrovinsky, Applied Physics

Letters 2004, 85, 1508.

[12] L. G. Sneddon, K. Su, P. J. Fazen, A. T. Lynch, E. E. Remsen, J. S. Beck, lUPACMacromolecular Symposium Inorganic and Organometalic Oligomers and

Polymers, Pure and Applied Chemistry 1991, 33, 199.

[13] S. Y. Rybakov, V. M. Sharapov, L. E. Gavrilov, Journal de Physique IV 1995, 5,

921.

[14] M. F. Hawthorne, Angew. Chem. Int. Ed. Engl. 1993, 950.

[15] R. N. Grimes, Journal ofChemical Education 2004, 81, 657.

[16] S. E. A. Gratton, M. C. Parrott, A. Adronov, Journal of Inorganic and

Organometallic Polymers and Materials 2005, 75, 469.



[18] S. R. Benhabbour, M. C. Parrott, S. E. A. Gratton, A. Adronov, Macromolecules

2007. 40, 5678.

[19] X. L. Wei, P. J. Carroll, L. G. Sneddon, Organometallics 2006, 25, 609.


[21] M. J. Pender, K. M. Forsthoefel, L. G. Sneddon, Pure and Applied Chemistry

2003, 75, 1287.

[22] M. J. Pender, P. J. Carroll, L. G. Sneddon, Journal of the American Chemical

Society 200\, 123, 12222.

[23] T. Thum-Albrecht, R. Steiner, J. DeRouchey, C. M. Stafford, E. Huang, M. Bal,

M. Tuominen, C. J. Hawker, T. Russell, Advanced Materials (Weinheim, Federal

Republic ofGermany) 2000, 12, 787.

[24] R. F. Barth, J. A. Coderre, M. G. H. Vicente, T. E. Blue, Clinical Cancer

Research 2005, 11, 3987.

[25] L. Zheng, R. J. Farris. E. B. Coughlin, Journal of Polymer Science, Part A:

Polymer Chemistry 2001, 39, 2920.

[26] J. A. Love, J. P. Morgan, T. M. Tmka, R. H. Grubbs, Angewandte Chemie,

International Edition in English 2002, 41, 4035.

[27] L. B. Luo. J. Tarn, D. Maysinger, A. Eisenberg, Bioconjugate Chemistry 2002,

13, 1259.

52

[28] F. A. Gomez, S. E. Johnson, M. F. Hawthorne, Journal ofthe American Chemical

Society \99\J1 3. 59\5.

[29] M. F. Ilker, K. Nuesslein, G. N. Tew, E. B. Coughlin, Journal of the American

Chemical Society im^, 126, 15870.

[30] S. Messaoudi, F. Anizon, B. Pfeiffer, M. Prudhomme, Tetrahedron 2005, 67,

7304.

[31] Y. Wang, J. Cai, H. Rauscher, R. J. Behm, W. A. Goedel, Chemistry—A European

Journal 2005. 77,3968.

[32] Y. C. Simon, E. B. Coughlin, Polymer Preprints (American Chemical Society,

Division ofPolymer Chemistry) 2005, 46, 111.

[33] R. H. Grubbs, Handbook ofMetathesis, Vol. 3, Wiley, John & Sons, Incorporated,

2003.

[34] D. E. Owens, N. A. Peppas, International Journal of Pharmaceutics 2006, 307,

93.

[35] R. Duncan, Nature Reviews Drug Discovery 2003, 2, 347.

[36] E. R. Gillies. J. M. J. Frechet, Journal of the American Chemical Society 2002,

124, 14137.

[37] Y. Nakamura, Y. Wan, J. W. Mays, H. latrou, N. Hadjichristidis, Macromolecules

2000, 33, 8323.

53

CHAPTER 3

RING-OPENING METATHESIS COPOLYMERIZATION OF CYCLOOCTENE

AND A CARBORANE-CONTAINING OXANORBORNENE

3.1 Introduction

As reported in the previous chapter, we have synthesized a novel carborane-

containing monomer 4 (silyl-protected oxanorbomene imide carborane: SONIC). Its

subsequent incorporation in homopolymers and amphiphilic diblock copolymers by ring-

opening metathesis polymerization has been successful.[l] Here, we wish to report the

incorporation of 4 in polyethylene-like materials by copolymerization with cyclooctene

(COE) followed by hydrogenation in the presence of/>-toluenesulfonylhydrazide (TSH).

The possibility to control the composition of the copolymer based on the feed ratio is

demonstrated and the optimization of the hydrogenation conditions are also discussed.

Preliminary results of the investigations of the morphological and thermal properties of

the copolymers, and the evaluation of the influence of molecular weight, hydrogenation

and composition upon these properties is reported. A model compound was also

synthesized and homopolymerized to determine the influence of the silyl-functionalized

carborane clusters on the physical properties of the polymer. Ultimately, these polymers

have elemental compositions making them suitable candidates for utilization in radiation

shielding materials.

54

3.2 Experimental

3.2.1 Materials.

All organic reactants and reagents were purchased from Aldrich Chemical Co and

used as received unless specified otherwise. Toluene was dried over sodium with

benzophenone as an indicator. Dichloromethane was obtained through Fisher, distilled

over calcium hydride and degassed with freeze-pump-thaw cycles. 0-carborane was

supplied by KatChem. Grubbs 1^' generation was purchased from Strem Chemicals.

Grubbs 3'^'' generation catalyst was synthesized according to the literature and stored

under nitrogen atmosphere. [2] Monomer 4 was synthesized as previously described in the

literature, the polymerization of this monomer by ROMP has also been described.[l] o-

Xylene was passed through an activated alumina column prior to use. p-

Toluenesulfonylhydrazide was purchased from Aldrich Chemical Co. and recrystallized

from benzene.

The nomenclature for the different compounds is as follow. Copolymers of 4 and

COE were named 12(XX)-T or 12(XX)-D. where T,and D, indicate the reaction solvents

toluene or dichloromethane respectively, and XX represents the molar percentage of

monomer 1 in the feed. For example, a polymer with a targeted composition of 75% of 4,

synthesized in toluene, is designated as 12(75)-T. Subsequent hydrogenation of the

materials will be indicated by an H in front of the descriptor. Therefore, the result of the

hydrogenation of a polymer with 50% SONIC originally synthesized in dichloromethane

will be noted: H-12(50)-D. Even though homopolymers of 4 were reported in the

previous chapter as 5, they will be reported as 12(100) in the present chapter to simplify

the discussion.

55

3.2.2 Instrumentation.

Gel permeation chromatography (GPC) measurements for the polymers were

performed in tetrahydrofuran (THF) at 1.0 mL/min using a Knauer K-501 Pump with a

K-2301 refractive index detector and a K-2600 UV detector, and a column bank




relative to polystyrene standards. The 'H NMR and '^C NMR were recorded at 300 MHz

and 100 MHz respectively on a Bruker NMR spectrometer at room temperature in

deuterated chloroform. For 'h NMR, the protons attached directly to the boron atoms of

the carborane cage integrate for 10 protons as broad multiplets due to couplings with

boron nuclei (5 (ppm) = 3.20-1.01 (br, lOH, BH)). Thermogravimetric analyses (TGA)

were performed on a TA-Instruments 2950 with a heating rate of 10°C per minute,

sweeping temperatures ranging from 25°C to 700°C under inert atmosphere. Differential

Scanning Calorimetry (DSC) measurements were performed on a Mettler-Toledo DSC

822e and a DuPont Instrument 2910 with a heating rate of 10°C per minute from 25°C to

250°C for the homopolymers (12(100)-D, H-12(100)-D, 14 and H-14), and from -50 °C

for the copolymers (12(XX) and H-12(XX), with XX < 100). Wide-angle X-ray

scattering (WAXS) patterns were recorded using a Paranalytical X-pert X-ray

diffractometer for angles ranging between 1 and 30 degrees. All samples were fine

powders and were pressed to obtain a smooth surface.

56

3.2.3 Synthesis and Spectral Data

Synthesis of 12(XX). The polymerization of copolymers with different feed ratios

was run alternatively in toluene or dichloromethane as follows. In a round bottom flask

purged with nitrogen and equipped with a stir bar, the desired amount of 4 (463.70 g/mol)

was dissolved in the reaction solvent so as to obtained a 0.2 mol/L solution. Using a

syringe, the desired amount of COE was added. A solution of Grubbs 1^' generation

catalyst was then introduced such that the final concentration of catalyst would be 1000

times less than that of the combined monomers. The reaction was allowed to proceed for

24 h and was stopped by addition of an excess of ethyl vinyl ether. The polymer was then

precipitated in cold methanol and filtered over sintered glass. The stringy solid was then

dried in a vacuum oven for 12 h at 40 °C. For NMR characterization see the discussion

section.

Hydrogenation ofthe polymers. The following is a typical experimental procedure

performed on the samples obtained in dichloromethane. In a 50 mL round-bottom flask

mounted with a condenser, the polymer (110 mg) and TSH (330 mg) were dissolved in

25 mL of o-xylene and the mixture was brought to reflux (130°C) under constant

agitation and with the slight nitrogen purge. After 2h the reaction was allowed to cool to

50°C and was then precipitated in methanol. The following is the NMR for 12(100)-D:

'H NMR (CDCI3): 5 (ppm) = 3.79 (br s, 2H), 3.41 (br s, 2H), 3.11 (br s, 2H), 1.07 (s,

9H), 1.33 (s, 6H); '^C NMR (CDCI3): 5 (ppm) = 175.88, 81.15, 80.16, 76.20, 52.22,

37.80, 35.16, 31.10, 28.45, 27.55, 20.40, -2.47.

Synthesis of exo-N-propyl-7-oxabicyclo[2,2,l]hept-5-ene-2J-dicarboximide 13.

In a dry 500 mL flask, exo-7-oxonorbomene imide (7.6 g, 46 mmol, 1 equiv.), propan-1-

57

ol (3.8 mL, 51 mmol, 1.1 eq) and triphenylphosphine (13.3 g, 51 mmol, 1.1 equiv.) were

dissolved upon stirring in 300 mL of freshly distilled dry tetrahydrofuran (THF). The

flask was kept under nitrogen pressure and cooled down to 0°C with an ice bath. After 5

minutes, diisopropylazodicarboxylate (DIAD) (3.2 mL, 16.26 mmol, 1.1 equiv.) was

added and the solution turned yellow. The reaction was allowed to react overnight ( 1 6 h)

affording a deep-yellow solution. The crude mixture was then concentrated in vacuo to

obtain a sticky yellow paste. The paste was then redissolved in a minimum amount of

THF and precipitated by dropwise addition into hexanes (800 mL). The precipitate was a

white powder with a slight reddish tint. The powder was then redissolved and precipitated

a second time. The precipitate was then recrystallized from boiling methanol followed by

cooling at -4°C, affording 9.5 g of white powder (78 % yield). 'H NMR (CDCI3): 5

(ppm) = 6.51 (s, 2H, CH=CH), 5.27 (s, 2H, CHO), 3.45 (t, 2H, J = 7.2 MHz, NCH2), 2.83

(s, 2H, CH-C=0), 1.60 (qt, 2H, J = 7.5 MHz, J = 7.2 MHz, CH2CH2CH3), 0.88 (t, 3H, J =

7.5 MHz, CH3); '^C NMR (CDCI3) 5 (ppm) = 176.37, 136.54, 80.91, 47.37, 40.53, 20.96,

11.15.

Polymerization of the model monomer 13 to afford polymer 14. The

polymerization of 13 was performed following the procedure employed for the synthesis

of 12(100)-D. 'H NMR (CDCI3): 5 (ppm) = 6.23 (bs, 0.95 H, CH=CH trans), 5.58 (bs,

1.05 H, CH=CH cis), 5.02 (bm, 1.05 H, CHO cis), 4.46 (bm, 0.95 H, CHO trans), 3.43

(bs, 2H, NCH2), 3.35 (s, 2H, CH-C=0), 1.72 (bs, 2H, CH2CH2CH3), 0.89 (bs, 3H, CH3);

'^C NMR (CDCI3) 6 (ppm) = 175.72, 131.91, 81.10, 52.38, 40.52, 31.01, 1 1.27; GPC (PS

std) : Mn = 91,600 g/mol, PDI = 1.07.

58

Hydrogenation ofthe model polymer-H-14. The hydrogenation procedure was the

same as that utilized for the obtention of H-5 and H-12 'H NMR (CDCI3): 5 (ppm) = 3.82

(bs, 2H, CHO), 3.42 (bs, 2H, CH2N), 3.11 (bs, 2H, CHC=0), 1.96 (bs, 4H, CH2

backbone), 1.57 (bs, 2H, CH2CH2CH3), 0.88 (bs, 3H, CH3), GPC (PS std) : Mp = 88.500

g/mol, PDl = 1.13.

rtv p

Figure 3.1 Ring-Opening Metathesis copolymerization of 1 and COE.

3.3 Results and Discussion

3.3.1 Copolymerization.

Since the homopolymerization of 4 has previously been described elsewhere, the

present discussion will focus on the statistical copolymerization of monomer 4 and COE

(Figure 3.1). Previous work in our laboratory has pointed out the possibility to obtain

strictly alternating structures by copolymerization of COE with oxanorbomene

monomers. [3] Other laboratories have reported similar observations. [4] In the present

investigations, it would be expected that consumption of the exo monomer 4, would

occur much more rapidly than that of COE leading to the formation of a tapered block

copolymer. This is clearly the case when the polymerization is carried out in

dichloromethane, as illustrated by the presence of the two strong signals at 5 = 5.3 (a

tram) and 6.1 ppm (d) characteristic of homopolymer sequences (Figure 3.2). It is

59

observed, however, for the copolymerization of 4 and COE conducted in toluene, that the

result is a much more randomized structures where alternation, although not strict

(Scheme 3.1), seems to prevail (Figure 3.2). Another way to evaluate the amount of

alternation consists in comparing the ratios of signals b cis/trans and b' cis/trans (Figure

3.2). As can be observed for 12(50)-T, and unlike 12(50)-D, the signal of b' is much

greater than the b counterpart which further illustrates the tendency towards alternation

obtained in the case of toluene as a solvent.

Scheme 3.1 The perfectly alternating structure of polymer 12(50).

1i

1

1

1

i

\ 11

•

\ 1 1

i

I

I r r

I

I i \ \

6.00 5.50 5 00 4 50

ppm(ll)

Figure 3.2 Illustration of the differences in alternation depending on solvent

polarity.

60

This notable difference can be accounted for by the difference in polymerization

rate upon changing the solvent. An initiation rate increase of 30% has been observed in

the literature upon altering the dielectric constant of the reaction medium when switching

from toluene (e = 2. 38) to dichloromethane (e = 8.9). [5] This phenomenon is attributed

to the stabilization of the products of the dissociation of the phosphine ligand from the

ruthenium complex. This displacement of the equilibrium towards the dissociated species

favors the homopolymerization of COE with respect to alternation by accelerating the

homopolymerization rate. Conversely, in the presence of a less polar solvent such as

toluene, the metal alkylidene is much more tightly bound to the phosphine and remains in

the active form for shorter times. This phenomenon contributes to a selectivity decrease

and favors the alternation of monomers 4 and COE. Since the catalyst spends a longer

time in its "dormanf state, it becomes less selective and has the tendency to coordinate to

whichever of the two monomers enters its sphere of coordination.

As far as incorporation ratios are concerned, it can be observed that they are

consistent with the feed ratios (Table 3.1). Also, it is to be noticed that in the case of the

copolymerizations in toluene, at ratios of SONIC:COE of 1:3 and 3:1 (Table 3.1, entries

12(75)-T and 12(25)-T), there are virtually no homopolymer sequences of the limiting

monomer as indicated by the absence of characteristic resonance in the NMR spectra. In

the case of dichloromethane as a reaction solvent, similar observations can be made. The

polymerizations in toluene seem to lead to the formation of much shorter chains. Again,

this could be explained by the fact that the polymerization rate is accelerated in

dichloromethane. Additionally, unlike ruthenium alkylidenes bearing a N-heterocyclic

carbene (NHC), complexes with two phosphines are much more prone to phosphine

61

recoordination as they do not benefit from the donor effect of the NHC. If recoordination

is disfavored by use a more polar solvent, it is expected that the molecular weights

attained should be greater (Table 3.1). Also, since the catalyst spends much less time in a

dormant state, the polymerization is less well-controlled leading to globally higher

polydispersity indices.

Table 3.1 Conditions and results for the polymerization of monomers 4 and COE.

Entry M„ (g/mol)' PDl' Molar Ratios^

SONIC COE

12(100)-D 58,600 1.09 100 0

12(75)-D 544,500 1.63 74 26

12(50)-D 135,900 4.32 49 51

12(25)-D 42,900 2.4 25 75

12(75)-T 55,300 1.15 77 23

12(50)-T 24,800 2 51 49

12(25)-T 25,800 2.61 23 77

As measured by GPC vs. polystyrene standards. ^ As measured by *H NMRspectroscopy by comparing the integrations of the oleflnic region with the

silylmethyl peak at 5 = 0.33 ppm.

3.3.2 Hydrogenation.

Previous studies in our group have demonstrated the possibility of using

arylsulfonyl hydrazide at high temperatures to hydrogenate polyoligomeric

silsesquioxane-containing polymers. [6] Several hydrogenation conditions were attempted

on different polymers, changing solvent (toluene vs xylenes), duration (from 1 to 16 h)

and the additive (tri-«-propylamine). Although Hahn reported the necessity of employing

a high-boiling amine to prevent any side reaction, in particular the protonation of olefmic

sites upon formation of p-toluenesufinic acid, it was observed that the amine actually

contributed to a sharp decrease of molecular weight upon hydrogenation. [7] This

62

observation is believed to be a result of the degradation of the polymer. Although the

mechanism is still unclear and is currently being investigated, it is suspected that the

amine interacts with the silyl group which leads in turn to the alteration of the periphery

of the carborane cluster. [8]

Figure 3.3 Conditions for the hydrogenation of polymer 12.

b

c,d

c,d

1r— T 1 1—I

1—I1 1

î

1 1

'

\

1 1'

1

1 1—T1

1

' 1

1—I

\

—I

1—I1

\ r

7.0 6.0 5 0 4 0 3 0 2 0 1 0 0 0

ChemicalShift (ppm)

Figure 3.4 Proton NMR spectrum of H-12(25)-D.

After several optimization steps, the most advantageous conditions were found

(Figure 3.3 and 3.4). Reaction temperatures and reaction times proved to have a key role

on the outcome of the reaction. The results for the hydrogenation are reported in Table

3.2. The hydrogenated product can be obtained in reasonably high yield with virtually no

63

remaining unsaturation as monitored by H NMR spectroscopy. Furthermore, no

significant increase in polydispersity can be recorded. Also, despite the net increase in

molecular weight by addition of hydrogen onto the C-C double bonds, the apparent

molecular weights of the hydrogenated materials are overall lower than their unsaturated

counterparts. This phenomenon can be accounted for by the fact that the chain becomes

more flexible as the double bonds are removed due to the free rotation about the newly

formed carbon-carbon single bonds. This increase in the degree of freedom allows for the

chain to adopt a much more compact conformation and therefore, an apparently smaller

hydrodynamic radius.

Table 3.2 Hydrogenation results for the polymers 5 and 12 synthesized in

dichloromethane.

EntryMn

(g/mol)^PDI' Yield

H-12(100)-D 43,900 1.05 88%H-12(75)-D 416,300 1.65 99%H-12(50)-D 115,000 3.92 98%H-12(25)-D 37,600 3.6 95%

Measured by GPC against polystyrene standards.

3.3.3 Thermogravimetric Analysis.

In this section, we describe the influence of molecular weight, unsaturations, and

the composition (copolymer and presence of carborane) on the thermograms. We also

synthesized model polymers 14 and H-14 in order to evaluate the influence of the cage

on thermal properties (Figure 3.5). To evaluate the influence of unsaturation and

molecular weight, two series of polymers were considered (12 and H-12). Thermal

64

decomposition for both series does not seem to be molecular weight dependent, as the

thermograms are superimposable. This superimposition stems from the fact that the

polymers are above the critical molecular weight for which the chain length would play a

role. As expected, the unsaturated polymer 12 shows a lower onset of decomposition

temperature than H-12, as the presence of allylic protons undermines the thermal stability

of the polymer (Table 3.3). Nevertheless, the double bonds favor the formation of char

through crosslinking, resuhing in higher char yields. Also, not surprisingly, when

comparing with the model compound 14, the hydrogenated version, H-14, with the

carborane cage leads to increased char formation upon pyrolysis for 12(100)-D, resp. H-

12(100)-D (Table 3.3). However, if the weight percent of the carborane cage matches the

increase in char for the unsaturated versions (12(100)-D v^. 14), it does not appear to be

so for the hydrogenated analogs (H-12(100)-D vs. H-14). Additionally, and as expected,

it can be noted that the char yield increases with the increase in carborane content.

14 H-14

Figure 3.5 Synthesis of model polymers 14 and H-14 to evaluate the influence of the

silylcarborane cage on thermal properties.

65

Table 3.3 Thermogravimetric analysis and differential scanning calorimetry results

of 12, H-12, Hand H-14.

EntryTo Td Char

EntryTo Td Char

(^C) (^C) Yield Co ("C) Yield

12(100)-D 153 370 31.6% H-12(100)-D 145 423 15.5%

12(75)-D 99 310 14.6% H-12(75)-D 88 410 1 1 .0%

12(50)-D 78 300 13.2% H-12(50)-D 91 407 10.2%

12(25)-D 32 241 9.0% H-12(25)-D 32 393 6.7%

12(0)-Db b

H-12(0)-Db b b

14 131 396 9.8% H-14 103 411 3.2%

According to reference [4]. Not measured.

3.3.3.1 DSC Analysis.

DSC analysis was used to study the effect of the new polymer structures and

molecular weights on the observed thermal transition (glass transition temperature (Tg),

melting temperature (Tm)). As observed for the TGA experiments, the molecular weights

do not seem to affect the Tg (data not shown here). However, a decrease by nearly 10 °C

was observed for the hydrogenated version H-12 with respect to their unsaturated

counterparts 12. This decrease can be explained by fact the free volume generated upon

hydrogenation. The latter confers flexibility to the backbone as it allows for the rotation

about the C-C single bond, thereby generating more free volume in the polymeric

structure. This phenomenon is also observed in the case of the model compound. Also,

the influence of the silyl protecting group on the aggregation of the carboranes in the

polymeric matrix is being evaluated.

3.3.4 Wide-Angle X-ray Scattering (WAXS).

The crystalline nature of 4 encouraged us to investigate the morphological

behavior of the homo- and copolymers containing carborane cages. We have previously

66

demonstrated in our laboratory, the possibility to drive self-assembly of inorganic-

organic hybrid copolymers through the crystallization of inorganic nano-building blocks

based on polyhedral oligomeric silsesquioxane (POSS) cages. [6,9] The aggregation of

POSS has been demonstrated to be the driving force for the formation of raft-like

structures and can lead to the formation of elastomers with physical crosslinks. [10]

However, despite the crystallinity of 4, no crystallization was observed in the case of

homopolymers, i.e. the highest loading possible (Figure 3.6 and 3.7). This dispersion can

be explained by the weakness of the intermolecular interactions between the boron

clusters. The aggregation of POSS depends chiefly on its periphery and is stronger in the

case of cyclopentenyl and phenyl peripheries.[ll] The presence of interlocked organic

side chains contributes greatly to the stability of the crystals made by these silicon oxide

clusters. Conversely, carboranes do not possess peripheral groups favoring

crystallization. Carborane clusters are known to be plastically crystalline, i.e. above a

certain temperature (approx. 120 K),[12] only their center of mass is located on a regular

lattice, which diminishes the likelihood of the clusters crystallizing within a polymeric

matrix.

67

-55-

>.

inc(D

wMiiiWKtHiij.^

10 20 30

29 (deg)

Figure 3.6 Wide angle X-ray scattering results for the series of polymers 3.

One could have thought that the crystalHzation of the boron clusters would have

been favored by the presence of more flexible segments of COE as well as by the

hydrogenation of the said chains. However, neither alternative to make the backbone

more flexible seemed to induce carborane crystallinity in these copolymer. We are

currently investigating what role the silyl group has on influencing this crystallinity, or

lack thereof. [8]

68

H-12(100)-D

H-12(75)D

H-12(50)D

H-12(25)D

2e (deg)

Figure 3.7 Wide angle X-ray scattering results for the series of polymers H-12.

The fact that the boron clusters do not aggregate could actually be advantageous.

In particular, their utilization as radiation shielding materials is envisaged (Appendix B).

Simulation studies by Singleterry et al. have highlighted the potential of '°B loaded

polyethylene as space survivable materials. [13] Additionally, Wilson et al. have pointed

out that polymeric materials are excellent candidates for space exploration because they

combine light weight, good and adjustable thermomechanical properties and are

relatively inexpensive to process. [14, 15] We believe that the present synthetic approaches

described here offer a level of control that could allow for tailoring of properties.

Furthermore, the elemental compositions allows for the thermalization of neutrons

through inelastic collisions with the hydrogens along the poly-ethylene like backbone as

well as neutron capture due to the high cross capture area of '*^B.[13,16]

69

3.4 Conclusions

We have reported the copolymerization of 4 and COE to obtain polyethylene-Hke

materials which incorporate carborane pendant groups. The reaction conditions for the

hydrogenation subsequent to the ROMP of the two monomers have been optimized. The

possibility to control the composition of the copolymer has been highlighted as well as

the influence of solvent polarity on the statistical polymerization. Thermogravimetric

analysis has shown enhanced thermal properties upon increasing the fraction of monomer

4 in the feed. Both differential scanning calorimetry and X-ray diffraction analyses

indicated the absence of crystallization of the boron clusters. Contrary to what could have

been expected, the hydrogenation and composition have no influence on the

crystallization behavior of the polymer.

3.5 References

[1] Y. C. Simon, C. Ohm, M. J. Zimny, E. B. Coughlin, Macromolecules 2007, 40,

5628.

[2] J. A. Love, J. P. Morgan, T. M. Tmka, R. H. Grubbs, Angewandte Chemie,

International Edition in English 2002, 41, 4035.

[3] M. F. Ilker, E. B. Coughlin, Macromolecules 2002, 35, 54.

[4] L. Morbelli, E. Eder, P. Preishuber-Pflugl, F. Stelzer, Journal of Molecular

Catalysis a-Chemical 2000, 160, 45.

[5] M. S. Sanford, J. A. Love, R. H. Grubbs, Journal of the American Chemical

Society 2001, 123, 6543.

[6] L. Zheng, R. J. Farris, E. B. Coughlin, Journal of Polymer Science, Part A:


[7] S. F. Hahn, Journal of Polymer Science, Part A: Polymer Chemistry 1992, 30,

397.

[8] Y, C. Simon, E. B. Coughlin, Submitted.

70

L. Zheng, S. Hong, G. Cardoen, E. Burgaz, S. P. Gido, E. B. Coughlin,


B. Seurer, E. B. Coughlin, Macromolecular Chemistry and Physics 2008, 209,

1198.

A. J. Waddon, E. B. Coughlin, Chemistry ofMaterials 2003, 75, 4555.

R. H. Baughman, Journal ofChemical Physics 1970, 53, 3781.

R. C. J. Singleterry, S. A. Thibeault, LaRC NASA, 2000.

J. W. Wilson, F. A. Cucinotta, M. H. Y. Kim, S. W., in 1st International

Workshop on Space Radiation Research and 11th Annual NASA Space Radiation

Health Investigators' Workshop, 2001.

J. W. Wilson, M. S. Clowdsley, F. A. Cucinotta, T. R.K., J. E. Nealy, G. DeAngelis, 2002.

B. W. Robertson, S. Adenwalla, A. Harken, P. Welsch, J. I. Brand, P. A. Dowben,

J. P. Claassen, Applied Physics Letters 2002, 80, 3644.

71

CHAPTER 4

SYNTHESIS OF POLYFLUORENES WITH PENDANT SILYLCARBORANES

4.1 Introduction

For a little over 30 years, conjugated polymers have stimulated the imagination of

chemists, physicists and material scientists alike, and the desire to tailor properties

through careful design has continued unabated. [1,2] Aside from the mere scientific

curiosity, this desire has been fueled by the multitude of applications for which these

compounds are used: antistatic coatings, electrochromic pannels, polymer light-emitting

diodes (PLEDs), photovoltaic devices, e/c.[3] However, one of the highly sought-after

features of these materials, i.e. extended conjugation through aromatic moieties, is also

one of their pitfalls. The rod-like nature of these systems contributes to the tendency of

conjugated systems to bundle and jc-stack. These phenomena are detrimental to the

processability of such systems and pose subsequent problems in terms of their utilization

in optoelectronic devices. [4,5] To circumvent these issues, chemists have devised

synthetic strategies to confer solubility and stability to conjugated polymers while

preserving their remarkable properties.

Notably, 9,9-disubstituted polyfluorenes (PFs) have emerged as a unique class of

blue-emitting materials for PLEDs. [3,4] The planarization of the structure by the carbon

bridge and the possibility for facile property tuning and solubility via functionalization at

the 9 position as well as their remarkable quantum efficiency have made PFs a

noticeable candidate in the field of optoelectronics. [6] Despite the presence of these

solubilizing groups, commonly alkyl groups, it has been observed that upon applying a

72

current or upon annealing, the chains have the tendency to aggregate and various groups

have explored methodologies to efficiently thwart this phenomenon. [5,7] Notably, Miller

et al. have successfully illustrated the possibility to use fourth generation dendrons via

end-capping as a means to efficiently contravene stacking. Additionally, Mullen et al.

have demonstrated the utilization of polyaromatic dendrons as a successful strategy to

address this unwanted behavior. [5]

The utilization of boron in conjugated systems often stems from its Lewis acidic

character, which makes the resulting compounds particularly attractive for sensor

applications, and recently, copolymers of dibenzoborole and fluorene have been utilized

as a route to detect anionic contaminants. [8] Another strategy to introduce boron in

conjugated systems revolves around the utilization of carboranes. Several groups have

utilized these inorganic clusters, both in the main chain or as side groups, to provide these

systems with electrochemical stability and novel electronic properties, whether in small

molecules or in polymers. [9- 12] Particularly, seminal work by Vicente et al. on pyrroles

and thiophene has underlined the advantage of introducing carboranes as a way to

reinforce the thermo oxidative resistance of electronic materials. [13,14]

In the present document, we report the synthesis of a novel fluorene monomer 17

disubstituted with bulky silylcarborane clusters. The homopolymerization of 17 using

microwave-assisted Yamamoto coupling, as well as its copolymerization with 2,7-

dibromo-9,9-dihexylfluorene 18 are described hereafter. Finally, the spectral properties of

the homo- and copolymers are investigated and practical applications are discussed.

73

TBDMS3 ÔH

17

Figure 4.1 Synthesis strategies to attain monomer 17. i. CH2CI2, TsCl,

pyridine(dropwise); ii. CH2CI2, 0 °C, CBr4, PPhj; iii. THF, tBuOK, 2,7-

dibromofluorene; iv. PhH/Et20 (2:1 V:V), tBuOK, 2,7-dibromofluorene.

4.2 Experimental Section

4.2.1 Materials.

All organic reactants and reagents were purchased from Aldrich Chemical Co and

used as received unless specified otherwise. Anhydrous benzene and diethyl ether were

dried over sodium with benzophenone as an indicator. Dichloromethane (DCM) was

obtained through Fisher, distilled over calcium hydride and degassed with freeze-pump-

thaw cycles. 0-carborane was supplied by KatChem.

74


Gel permeation chromatography (GPC) measurements for the polymers were

performed in tetrahydrofuran (THF) at 1.0 mL/min using a Knauer K-501 Pump with a

K-2301 refractive index detector and a K-2600 UV detector, and a column bank





'H NMR, "B NMR and '^C NMR were recorded at 300 MHz, 128 MHz and 100

MHz respectively on a Bruker NMR spectrometer at room temperature in deuterated

chloroform. The individual NMR spectral assignments do not list the carborane B-H

resonances. Due to the quadrupolar nature of boron, the resonances for the 10 B-H are

observed as broad multiplets (6 = 3.20-1.01 ppm). The integration of these multiplets

accounts for 10 H. Mehing points were measured with a mehing point apparatus

Electrochemical Mel-Temp in a capillary tube. For polymers 18, the number in

parenthesis represents the percentage of monomer 17 in the feed ratio.

4.2.3 Synthesis and Spectral Data

Preparation of 3-[2-(tert-butyl-dimethylsilanyl)-l,2-dicarha-closo-

dodecaboran(12)-l-yl]-propan-l-p-toluenesulphonate 15. [2-(/err-butyl-

dimethylsilanyl)-l,2-dicarba-c/o5o-dodecaboran(12)-l-yl]-propan-l-ol 1 (0.500 g, 1.5

mmol, 1 equiv.) was placed into a 50 mL two neck round bottom flask and flushed with

nitrogen. DCM (1.5 mL, freshly distilled from CaHi) was added and the solution was

75

cooled to 0°C. /7-Toluenesulfonylchloride (0.451 g, 2.3 mmol, 1.5 equiv.) was added

during a slight nitrogen overpressure, pyridine (0.25 mL, 0.248 g, 3.6 mmol, 2 equiv.)

was subsequently added. The reaction mixture was stirred at 0 °C for 4 h and the course

of reaction was followed by TLC (hexane/ethyl acetate, 3:1). After completion of the

reaction, ether (40 mL) were added, and the organic layer was washed with 40 mL of

each water, IM HCl and a 5% NaHCOs solution. The ether phase was then dried over

MgS04 and concentrated in vacuo to give 0.504 g of a white powder (71 % yield).

Recrystallization from acetonitrile afforded 0.41 1 g of pure product 15. (68% yield) High

Resolution MS (FAB-): m/z calcd 47L3296, found 471.3257; NMR (CDCI3): 6 (ppm)

= 7.76 (d, J= 8.35, 2H), 7.36 (d, J= 7.36, 2H), 3.99 (t, J,= 5.63, 2H, CH2OTS), 2.29 (m,

2H, CH2CH2OTS), 1.85 (m, 2H, CHs-Cage), 1.03 (s, 9H, CCH3), 0.31 (s, 6H, SiCHa); '^C

NMR (CDCI3): 5 (ppm) = 145.25, 132.63, 130.06, 127.85, 80.07, 77.47, 76.54, 68.80,

34.14, 29.37, 27.51, 2L67, 20.32, -2.52; m.p: 101 °C.

Preparation of l-bromo-3-[2-(tertbutyl-dimethylsilanyl)-L2-dicarba-closo-

dodecaboran(l 2)-1-yl]propane 16. [2-(êr/-butyl-dimethylsilanyl)-l,2-dicarba-c/o5o-

dodecaboran(12)-l-yl]-propan-l-ol 1 (500 mg, 1.58 mmol, 1 equiv.) and

carbontetrabromide CBr4 ( 785 mg, 2.37 mmol, 1.5 equiv.) were placed into a 50 mL

two-neck round-bottom flask and flushed with nitrogen. DCM (6 mL) was added and

after cooling the mixture to 0°C, triphenylphosphine (621 mg, 2.37 mmol, 1.1 equiv.)

was added to the solution with an slight nitrogen overpressure. After 3 hours of stirring,

the reaction solution was concentrated in vacuo and EtOH was added in order to

crystallize. After filtration, 474 mg of a white powder were obtained. (Yield 80%) High

Resolution MS (FAB-): m/z calcd 379.2374, found 379.2380; 'H NMR (CDCI3): 5 (ppm)

76

= 3.38 (t, 2H, CHzBr, J = 6 Hz), 2.39 (m, 2H, CH2CH2CH2), 2.08 (m, 2H, CHz-Cage),

1.10 (s, 9H, CH3C), 0.36 (s, 6H, CHsSi), '^C NMR (CDCI3): 5 (ppm) = 80.31, 76.36,

36.90, 32.54, 32.43, 27.78, 20.55, -2.23; m.p.: 91 °C.

Preparation of 2,7-dibromo-9,9-di[15]fluorene 17a. In a 50 mL round-bottom

flask flushed with nitrogen, 2,7-dibromofluorene (0.137 g, 0.425 mmol, 1 equiv.) and [2-

(?er/-buty1-dimethyIsilany1)- 1 ,2-dicarba-c/o50-dodecaboran( 1 2)- 1 -yl]-propan- 1 -p -

toluenesulphonate (0.5 g, 1.062 mmol, 2.5 equiv.) were dissolved in freshly distilled THF

and cooled to 0 °C. t-BuOK (1.3 mL of IM solution in THF, 3 eq ) was introduced

dropwise with a syringe over a period of 30 min. The solution was then heated to 40 °C

and the solution turned purple. After 1 day, the reaction was stopped by adding water (20

mL) and the product was extracted with 3 x 20 mL of DCM. The organic phases were

gathered and dried in vacuo to afford a sticky yellow solid which was recrystallized in

methanol (Yield 30%). For Characterization see 17b.

Preparation of 2, 7-dibromo-9,9-di{3-[2-(tertbutyl-dimethylsilanyl)-l,2-dicarba-

closo-dodecaboran(12)-l-yl]propane}fluorene from compound 17b. In a 25 mL 2-neck

round-bottom flask, 2,7-dibormofluorene (0.5g, 1.54 mmol, 1 equiv.) and tBuOK (415

mg, 3.70 mmol, 2.4 equiv.) were dissolved in 15 mL of a 4:1 mixture (V:V) of benzene

and diethylether. Upon addition of the solvent mixture, the solution turned deep purple.

To the solution, 3 (1.46 g, 3.86mmol, 2.5 equiv.) was added. The mixture was allowed to

react overnight and turned dark orange. To terminate the reaction, ethyl acetate (10 mL)

and water (20 mL) were added to the reaction. A slurry formed and was filtered. The

filtrate was washed with additional water (10 mL) and the solid was set aside. The

organic phase was dried over magnesium sulfate and concentrated in vacuo to afford a

77

yellow solid. The solid was rinsed with methanol to remove any remaining bromide. The

solid resulting from the filtration of the slurry was dissolved in dichloromethane (5 mL)

and methanol (20 mL) and the solution was concentrated in vacuo to give a yellow solid.

Both solids were combined and identified as monomer 17b (Yield = 65%). High

Resolufion MS (FAB-): m/z calcd 921.5210, found 920.5282; NMR (CDCI3): 5 (ppm)

= 7.6 (d, 2H, Jortho = 8.1 Hz), 7.53 (dd, 2H, Jonho = 8.1 Hz, Jêta = 1-5 Hz), 7.33 (d, 2H,

Jmeta = 1-5 Hz), 1.91 (t, 4H, J = 8.4 Hz), 1.82 (t, 4H, 7.8 Hz), 1.00 (s, 18H, CCH3), 0.80

(bm, 4H, CH2CH2CH2), 0.17 (s, 12H, SiCHj), '^C NMR (CDCI3): 5 (ppm) = 150.28,

139.09, 131.41, 125.93, 122.13, 122.04, 81.18, 76.12, 54.86, 39.30, 37.69, 37.60, 24.42,

20.44, -2.65;; m.p. = 235 °C.

Microwave-assisted of homo and copolymerization 18. In a microwave tube

equipped with a stir bar, the monomer (1 equiv.) was introduced as well as bipyridine

(2.2 eq). The tube was then pumped into a glove box and Ni(COD)2 (2.3 equiv.) was

added. The tube was sealed and taken out of the glove box. Additional COD (2.7 equiv.)

was added and the reagents were dissolved in 4 mL of a toluene:DMF (4:1) mixture. The

tube was quickly degassed and filled with nitrogen twice. The tube was then introduced

in a microwave apparatus and the solution was allowed to react for 20 min at 130 °C. The

solution was then filtered using a syringe mounted with filter paper as well as a 0.2 nm

anodisc filter and precipitated in 20 mL of a solution of acidified methanol (0.5M HCl).

A yellowish solid was recovered and identified as the desired polymer by 'H NMR

(Figures 4.2 and 4.3).

78

Results and Discussion

79

In order to synthesize monomer 17, a monofunctional silylcarborane moiety had

to be obtained. In chapter 2, a reliable method to obtain [2-(êrr-butyl-dimethyl-silanyl)-

l,2-dicarba-c/o5'o-dodecaboran(12)-l-yl]-propan-l-ol 3 is reported. [ 1 6] The conventional

approach to obtain 9,9-disubstituted fluorenes involves deprotonating the benzylic bridge

using two equivalents of a base, and subsequently adding in excess of an electrophile,

usually an alkylbromide.[17] To emulate this strategy, the connectivity of 3 had to be

reversed so as to obtain an electrophilic moiety and this has been done using two routes

(Figure 4.1). First, using p-toluenesulfonyl chloride, the alcohol was tosylated affording

compound 15. [18] Alternatively, the connectivity reversal was undertaken by means of

an Appel reaction in the presence of triphenyl phosphine and carbon tetrabromide to

obtain compound 16. [19]

The next step was the coupling of 2,7-dibromofluorene with 2 or 3 to synthesize

the desired monomer 4 (Figure 4.1). After several optimization steps, the solvent was

chosen to be a 2:1 (V:V) mixture of benzene and diethylether. Remarkably, in spite of the

steric hindrance of the silylcarborane, no monosubstituted fluorene was observed or

recovered. Once the monomer was fully characterized, its polymerization was

undertaken. In order to homo- and copolymerize 4, microwave-assisted Yamamoto

coupling was performed (Figure 4.4). This nickel-mediated coupling usually proceeds

under mild conditions in excellent yields. [20] However, several groups have highlighted

the interest of utilizing microwave-assisted aryl-aryl couplings to accelerate the screening

process for novel polymeric semiconductors. [21] Additionally, through a significant

reduction of the formation of side products, the yields of the reaction are often increased

80

making microwave heating an ideal candidate for the laboratory synthesis of libraries of

optoelectronic materials. [22]

18(50)

Figure 4.4 Microwave assisted polymerization of 17: (a) homo and (b)

copolymerizations witii 2,7dibromo-dihexylfluorene.

For the Yamamoto protocol, the reaction sequence is reported to proceed through

an oxidative addition followed by disproportionation, and finally reductive elimination to

obtain the diaryl moiety. The last step is essential so as to understand some of the

limitations that one can face while using sterically hindered molecules. Under the current

conditions, the presence of bipyridine which binds to two adjacent coordination sites

facilitates the elimination of the aryl to form the covalent C-C bond. While this step is

crucial for the polymerization of 17, one can easily understand that, as the polymer starts

to grow, it becomes harder and harder for the aryl chains to approach each other, as the

81

silylcarborane groups contribute to steric crowding of the chains. This phenomenon

makes the hkelihood of two aryl moieties being in two adjacent coordination sites less

likely, as molecular weight increases, leading to an eventual plateau of molecular weight.

This trend has been observed for the synthesis of 18(100). The reaction temperature was

varied from 100 °C to 150 °C without any observable increase of molecular weight. The

number average molecular weight was found to plateau at approximately 7,000 g/mol

which, if the end of the polymers were to be brominated, corresponds to a degree of

polymerization, DPn = 8-9. This number is obviously a crude approximation since the Mn

are measured vs polystyrene standards and do not take into account the rigid nature of

18(100), but they allow us to get a sense how efficient the reaction was.

6 5

Mn = 1 3.000 gimol Mn = 7^0C>

POI = 2.15 POP =1.73

Elution Time (mrn}

Figure 4.5 Gel permeation chromatograms for polymers 18(100) and 18(50).

In the case of copolymerization, polymer 18(50) was found to attain higher

molecular weights, which can be explained by the diminution of steric hindrance with the

introduction of linear «-hexyl side groups. This increase in molecular weight is

corroborated by the red shift in the emission spectrum of 18(50) with respect to 18(100)

82

(Figure 4.6B). This displacement towards the high wavenumbers is consistent with the

molecular weight of 18(100) being below the threshold (~ 10 units) after which

conjugation length is no longer affected by the DPn.[4] Additionally, the fluorescence

emission and UV absorption sharpen with higher MW, consistent with studies of other

oligomeric polyfluorenes.[15]

260 280 300 320 340 360 380 400 420 440 460 480 500-v.^^ : 1

.,

• 1 .1

. 1 .

Wavelength (nm) 300 350 400 450 500 550

Wavelength (nm)

Figure 4.6 UV absorption (left) and emission spectra (right) for polymers 18.

Similarly to the work by Shim, Wei and Tang where polyhedral oligomeric

silsesquioxane cages were added as a way to enhance thin film stability of PFs,[7,23,24]

the present work is thought to provide an elegant alternative to provide enhanced

resitance to thermal treatment. The behavior of the thin films is currently being

investigated so as to determine to what extent silylcarboranes contribute to stabilizing

PFs structures upon annealing. More importantly, polymers 18 are thought to be

interesting materials for neutron detection. [25] The high boron content coupled with the

83

high neutron capture area of '^B could potentially lead to a pathway for the detection of

fissile materials.

Several routes could contribute to the detection of neutrons. First, the ionizing

particles emitted upon capture of a thermal neutron can cause ionization of the

conjugated backbone leading to changes in its emission. Alternatively, one could utilize

the secondary gamma radiation to detect the presence of a neutron. Pei et al. have

demonstrated the use of PFs blends with dyes and gamma sensitizers for the detection of

gamma rays. [26] Inspired by this methodology, the utilization of carborane-containing

PFs could offer an interesting alternative to costly gas chamber detectors. Finally, studies

to introduce the carborane in the backbone are underway. This last approach is thought to

be even more promising for neutron detection, in that the conjugation of the polymer

would be directly modified by the loss of a-aromaticity upon neutron capture. Moreover,

the electronics of the subsequent polymers might lead to electrochemically stable PFs

with unique emission spectra.

4.4 Conclusions

We have successfully developed a new monomer, 17, that allowed for the

synthesis of polyfluorenes with bulky silylcarborane side chains. It was observed that the

molecular weights of the homopolymers was constrained by steric limitations and that its

fluorescence maximum was blue-shifted with respect to conventional fluorenes. To

remediate this phenomenon, copolymerization with 2,7-dibromo-9,9-dihexylfluorene was

undertaken leading to a significant increase in molecular weight. Both homo- and

copolymerizations studies were performed using microwave-assisted Yamamoto

84

couplings. Finally, we have alluded to some of the potential applications of such

materials, including stabilization upon annealing as well as utilization in neutron

detection, and alternative strategies incorporating carboranes in the main chain have been

depicted and are currently being investigated.

4.5 References

[1 ] A. J. Heeger, Reviews ofModern Physics 2001, 73, 68 1

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[2] A. Moliton, R. C. Hioms, Polymer International 2004, 53, 1397.

[3] M. Leclerc, Journal of Polymer Science, Part A: Polymer Chemistry 2001, 39,

2867.

[4] D. Neher, Macromolecular Rapid Communications 2001, 22, 1366.

[5] S. Setayesh, A. C. Grimsdale. T. Weil. V. Enkelmann, K. Mullen, F. Meghdadi,

E. J. W. List, G. Leising, Journal of the American Chemical Society 2001, 123,

946.

[6] M. Beinhoff, A. T. Appapillai, L. D. Underwood, J. E. Frommer, K. R. Carter,

Langmuir 2006, 22, 241 1.

[7] J. Lee, H. J. Cho, N. S. Cho, D. H. Hwang, J. M. Kang, E. Lim, J. I. Lee, H. K.

Shim, Journal ofPolymer Science Part a-Polymer Chemistry 2006, 44, 2943.

[8] V. D. B. Bonifacio, J. Morgado, U. Scherf, Journal of Polymer Science Part a-


[9] D. G. Allis, J. T. Spencer, Journal ofOrganometallic Chemistry 2000, 614, 309.

[10] D. G. Allis, J. T. Spencer, Inorganic Chemistry 2001, 40, 3373.

[11] H. M. Colquhoun, P. L. Herbertson, K. Wade, L Baxter, D. J. Williams,


[12] R. Hamasaki, M. Ito, M. Lamrani, M. Mitsuishi, T. Miyashita, Y. Yamamoto,Journal ofMaterials Chemistry 2003, 13, 21.

[13] B. Fabre, S. Chayer, M. G. H. Vicente, Electrochemistry Communications 2003,

5, 431.

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E. Hao, B. Fabre, F. R. Fronczek, M. G. H. Vicente, Chemical Communications

2007, 4387.

J. H. Jo, C. Y. Chi, S. Hoger, G. Wegner, D. Y. Yoon, Chemistry-a European

Journal 2004, 10, 2681.

Y. C. Simon, C. Ohm, M. J. Zimny, E. B. Coughhn, Macromolecules 2007, 40,

5628.

G. Saroja, P. Z. Zhang, N. P. Emsting, J. Liebscher, Journal of Organic

Chemistry 2004, 69, 987.

G. Eghnton, M. C. Whiting, Journal ofthe Chemical Society 1950, 3650.

T. W. Baughman, J. C. Sworen, K. B. Wagener, Tetrahedron 2004, 60, 10943.

T. Yamamoto, A. Morita, Y. Miyazaki, T. Maruyama, H. Wakayama, Z. Zhou, Y.

Nakamura, T. Kanbara, S. Sasaki, K. Kubota, Macromolecules 1992, 25, 1214.

K. R. Carter, Macromolecules 2002, 35, 6151

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F. Galbrecht, T. W. Bunnagel, U. Scherf, T. Farrell, Macromolecular Rapid

Communications 2007, 28, 387.

Q. Peng, M. J. Li, S. Q. Lu, X. H. Tang, Macromolecular Rapid Communications

2007, 28, 785.

C. H. Chou, S. L. Hsu, K. Dinakaran, M. Y. Chiu, K. H. Wei, Macromolecules

2005, 38, 745.

A. J. Peurrung, Nuclear Instruments & Methods in Physics Research Section a-

Accelerators Spectrometers Detectors and Associated Equipment 2000, 443, 400.

Y. S. Zhao, H. Z. Zhong, Q. B. Pei, Physical Chemistry Chemical Physics 2008,

10, 1848.

86

CHAPTER 5

DEVELOPMENT OF SILYLCARBORANE MONOMERS FOR LITHOGRAPHY

5.1 Introduction

Carboranes, and more specifically icosohedral carbaboranes, have been utilized in

various areas of research, including boron neutron capture therapy,[l-3] non-linear

optical materials and super-acid chemistry. [4,5] Recently, carborane-containing polymers

have shown promising results in a variety of nanotechnological applications, [6] and more

specifically in lithographic systems. [7-9] For instance, Ober has synthesized boron-

containing polymeric resists for EUV lithography starting with poly(styrene-Z)- 1,2-

butadiene) copolymers followed by a post-polymerization functionalization approach

employing the pendant olefins and a hydroboration/hydroxylation procedure to attach

pendant carborane cages. [7] The advantage of tethering inorganic clusters to a polymeric

matrix is that both the processability of polymers and the etch resistance of inorganics are

combined within a single material. The resistance of inorganic clusters stems from the

potential of forming non-volatile oxides upon treatment with an oxygen plasma. Boron

clusters are particularly interesting from the standpoint of generating novel of resists

because of their transparency to UV, and particularly extreme UV.[10]

With applications ranging from microelectronics to protein nanoarrays,[l 1,12]

nanoimprint lithography (NIL) is a very useful technique whose domain of utilization is

continuously expanding thanks to its ease of implementation and high-throughput

capability. [13] Nanoimprint lithography is intriguing from a cost perspective since

imprint systems do not require the sophisticated optics of conventional steppers. Rather,

87

imprint lithography uses polymers that harden while conforming to a physical template

upon exposure to ultraviolet light or upon a thermal actuation. In particular, UV

nanoimprint lithography (UV-NIL) limits pattern distortion and accelerates the

patterning process. [14] It is therefore a particularly attractive nanopatteming method. As

UV-NIL grows into a widespread patterning technique, the composition of UV-

crosslinkable resists becomes accordingly more and more diversified and sophisticated.

One can draw similarities among the formulations used in conventional photoresists.[15]

These comprise a series of monomers, for polymerization (monofunctional), crosslinking

and etch resistance, as well as a UV-sensitive free radical initiator. All of these

components are dissolved in a suitable solvent to allow for spin-casting. Additionally, the

viscosity of the ensemble is controlled to permit low-temperature embossing.

One of the most critical material components in the imprint lithographic process is

the photopolymerized resist layer; sometimes this resist layer is called the etch barrier or

imaging layer. The resist polymer chemistry needs to be designed so that it provides

higher etch resistance (selectivity) than the underlying layer which allows for pattern

transfer. While NIL resists that contain no inorganic additives have been used to make

patterned magnetic media with features as small as 35 nm, performance is limited by the

innate material properties of the resist layer. [16] Several advances have been made to

improve the properties of resists for NIL. One of the challenges associated with the

fabrication of metalized features at the nanoscale resides in the fabrication of overhang

structures that are convenient for the lift-off step. Matsui et al. have elegantly addressed

the issue of lift-off by utilizing water-soluble poly(vinyl alcohol) as the replicated

material. [17] This method is all the more interesting as it opens new perspectives in terms

88

of "green chemistry". However, such a technique requires the use of thermal NIL which

could eventually pose problems for the replication of small features in addition to the

associated costs. Willson et al. have shown more recently a method whereby the

imprinted resist could be un-crosslinked to allow for facile stripping of the copolymer

network, constituting the resist.[15] Carter has demonstrated an improved nanoimprint

lithographic process involving the pre-curing using a commercial polyurethane resist

which was used to make transistor devices after lift-off. [16]

Introduction of inorganic materials into resists has been a common route for

increasing oxygen plasma etch resistance. For example, the Willson group embraces the

use of siloxane-containing aerylate monomers in their NIL resist formulations. [14]

Carter recently reported the use of phosphazene-containing monomers in UV-NIL

formulations leading to excellent etch resistance properties. [18]

Lift-off is a particular concern when the mask features are shallow.[19] In order to

obtain a homogeneous pattern across a silicon wafer regardless of its roughness, it is

preferable to obtain features with high aspect ratio. That is why one must design and

formulate resists that will provide sufficient etch resistance to allow for pattern

amplification (Scheme 5.1). This property will facilitate pattern transfer as it eases the

lift-off step, by allowing the solvents to penetrate below the metalated features. This is

critical for the broader implementation ofNIL.

89

Scheme 5.1 Illustration of the use of an etch-resistant imprint layer for pattern

amplification in metallization processes.

Unamplified features Amplified features

Metallation

Lift-off

Partial lift-off

Unresolved pattern

In this report, the synthesis of a well-defined acrylate monomer containing both

boron and silicon and its incorporation into a UV-NIL resists is described. The resistance

to oxygen plasma etching is compared to a conventional resist formulation. We then take

advantage of the etch resistance of silyl-fiinctionalized carboranes to enable the

fabrication of high aspect ratio features. Microscopy combined with profilometry was

utilized to demonstrate pattern amplification. The patterns were subsequently metalized,

and the lift-off step was shown to be improved by the presence of boron and silicon in the

resist formulation.

5.2 Experimental Section

5.2.1 Materials.

All solvents and reagents were obtained from Aldrich and VWR and were used

without further purification unless specified otherwise. Single sided polished mechanical

grade 1.5" silicon wafers were purchased from University Wafer. Ethoxylated bisphenol

A dimethacrylate from Sartomer, methanol and chlorodimethyloctylsilane 97%, from

Fisher, 2-ethyl-2-(hydroxymethyl)- 1,3 -propanediol triacrylate, 2,2-dimethoxy-2-

90

phenylacetophenone, 2-hydroxyethyl methacrylate (HEMA) 98%, «,«'-

azoisobutyronitrile (AIBN) 98%, 1 -dodecanethiol 98%, 3-(trimethoxysilyl)propyl

methacrylate 98%, propylene glycol methyl ether acetate (PGMEA), from Sigma-

Aldrich, Gold 99.999% (Kurt J. Lesker), chromium (R. D. Mathis), were used as

received. The silylcarboranylpropanol 3 was prepared as previously described.[20,21]

Patterned silicon wafers containing test patterns and transistor structures were fabricated

by known photolithographic processes.


'H NMR and '^C NMR were recorded at 300 MHz and 100 MHz respectively on

a Bruker NMR spectrometer at room temperature in deuterated chloroform. The

individual NMR spectral assignments do not list the carborane B-H resonances. Due to

the quadrupolar nature of boron, the resonances for the 10 B-H are observed as broad

multiplets (5 (ppm) = 3.20-1.01) . The integration of these multiplets accounts for 10

hydrogens. Gel permeation chromatography (GPC) measurements for the lift-off layer

polymer were performed in tetrahydrofuran (DMF) at 1.0 mL/min using a Knauer K-501

Pump with a K-2301 refractive index detector and a K-2600 UV detector, and a column

bank consisting of two Polymer Labs PLGel Mixed D columns at 40°C. All other




Photopolymer Mold Preparation. Glass cover slips of #2 thickness from Fisher

were rinsed with acetone, isopropanol and dried under a stream of N2. The surface of the

91

glass was then activated by exposure to 100 millitorr oxygen plasma at 30 W for 7 min.

Immediately after activation the glass pieces were immersed in a dry, N2 purged toluene

solution containing 3-methacryloxypropyl trimethoxysilane (1% v/v) and heated at 80°C

for 12 hrs to assemble an adhesion monolayer. Patterned Si masters were cleaned by

exposure to O2 plasma for 3 min, coated with chlorodimethyloctylsilane, and heated to

130 °C for 20 min to create a protective alkyl release layer to ensure proper separation of

the cured photopolymer mold. Polymeric relief structures were formed on the treated

glass by placing a small drop (~ 50 |il) of a photocurable acrylate resin (Formulation A)

containing ethoxylated bisphenol A dimethacrylate 76.5 wt %, 2-ethyl-2-

(hydroxymethyl)-l,3-propanediol triacrylate 23.2 wt %, and 2,2-dimethoxy-2-

phenylacetophenone 2.5 wt % as initiator on the silicon master and carefully laying a

piece of treated glass over the drop allowing capillary forces to spread the resin between

the two surfaces. The two pieces were then exposed to 365 nm UV light to cure the resin.

Careful separation of the two surfaces yielded nano-pattemed features bonded to the glass

slide. A release layer was applied over the cured polymer features to aid separation

during the contact molding process.

Contact Molding with Etch Resist. Si substrates were cleaned by rinsing with

THF, acetone, and isopropanol, and blown dry with a stream of N2.

Poly(hydroxyethylmethacrylate) (PHEMA) (6.5 wt% in methanol) was applied to the

substrate and spun at 3000 rpm for 10 sec followed by baking at 130 °C for 30 sec

forming a 180 nm thick PHEMA film. An adhesion promoter, 3-(trimethoxysilyl)propyl

methacrylate, as was then applied and spun at 3000 rpm for 5 sec and the sample was

baked at 130 °C for 1 min. Excess adhesion promoter was washed off by spinning under

92

a pure stream of PGMEA for 15 sec at 3000 rpm followed by drying with N2.

Photopolymer by itself or loaded with 10 wt% carborane-acrylate, diluted in PGMEA to

10 wt% overall, and filtered through a 0.45 îm syringe filter, was then applied and spun

at 3000 rpm for 1 5 sec.

Immediately after spin coating, a mold was placed directly on the photopolymer

film and the setup was inserted into the NX-2000 imprinter. After pressurizing to 75 psi

the photopolymer was cured by 365 nm UV light for 30 sec. Release of the sample from

the mold yielded patterned substrates.

Etching, metal deposit, and lift-off step. Patterned films were etched in a Trion

Technologies Phantom III inductively couple plasma (ICP) reactive ion etcher (RIE)

under 250 milliTorr of O2 pressure at a flow rate of 49 seems, with ICP and RIE power of

500 W and 25 W, respectively, until the underlying silicon wafer was exposed in the

recessed regions throughout the imprint (-80 sec for photopolymer and -105 sec for

photopolymer/carborane acrylate). Etched wafers were coated with approximately 2 nm

of chromium followed by 10 nm of gold by vacuum evaporation. Lift-off was achieved

by sonication in warm methanol for 5 to 10 min followed by a methanol rinse.

5.2.3 Synthesis and Spectral Data.

Synthesis of silylcarborane acrylate 19. In a dry round-bottom flask,

silylcarboranylpropanol (1 equiv.) was dissolved in freshly distilled ether. The solution

was placed under a nitrogen flow with constant agitation, and triethylamine (1.5 equiv.)

was added dropwise with a syringe. The mixture was cooled to 0 °C and acryloyl

chloride (1.3 equiv.) was added dropwise to the solution. Upon addition, a white

93

precipitate formed indicating of the formation of the triethylammonium salt. The mixture

was then allowed to warm up to room temperature and stirred for one hour. A solution of

saturated brine was then added and the organic phase and aqueous phase were separated

in a separatory funnel flask. The aqueous phase was further extracted with 2 x 50mL of

diethyl ether. The organic phases were combined and dried over MgS04 and concentrated

in vacuo to afford a yellowish powder. The powder was then dissolved in boiling hexanes

and recrystallized at -4 °C (Yield = 73%). 'H NMR (CDCI3, 400MHz): 5 (ppm) = 6.40

(q, IH, Jtrans= 16Hz, Jgem = 1 .6Hz), 6.07 (q, IH, Jcs = 9.2Hz, Jtrans= 1 6Hz), 5.85 (q, IH,

Jgem = 1.6Hz, Jcs = 9.2Hz), 4.14 (t, 2H, CH2O), 3.20-1.01 (br, lOH, BH, CH2, CH2CB),

1.05 (s, 9H, SiCH3), 0.26 (s, 6H, CCH3); '^C NMR (CDCI3): 165.93, 131.35, 127.96,

80.51, 76.25, 63.13, 34.73, 29.38, 27.59, 20.35, -2.49.

Synthesis of poly(hydroxyethylmethacrylate) (PHEMA). Ethanol (7.5 mL) was

charged in a 25 ml round bottom flask and nitrogen was bubbled for 5 minutes. AlBN

(0.07 g, 0.43 mmol), HEMA (5.37 g, 5 mL, and 41.31 mmol) and dodecane thiol (0.43 g,

0.5 mL) were dissolved in the ethanol, the flask was sealed with a rubber stopper, and the

solution was heated under N2 at 60°C for 4 hours with stirring. The solution was cooled

and precipitated dropwise into hexanes. The polymer was filtered, washed with hexanes

and dried to obtain polyhydroxyethylmethacrylate (PHEMA) (4.5 g, 84%) as a white

solid. GPC data (in DMF): Mn=32,000 g/mol, PDI = 1.37.

94

OH

a) Dry EtjO, NEtg

b) 0"C,

5.3 Results and Discussion

We focused on developing a novel type of etch resistant monomer to facilitate the

lift-off process in the case of shallow patterns allowing for the fabrication of cleaner

metalated structures by NIL. The synthesis of silylcarborane acrylate 19 is depicted in

Figure 5.1. The optimized preparation of 3 that was based on a previous synthesis

published by Hawthorne is described in Chapter 2.[21] The incorporation of a silyl group

on the carborane serves a dual purpose. In the first case the steric demands of this group

ensures monosubstitution of ortho carborane allowing for the high yield preparation of 3.

Additionally, the presence of silicon will contribute to reinforcing the overall etch

resistance of the material by adding one more element capable of forming a stable non-

volatile oxide upon oxygen plasma treatment. The slow dropwise addition of acryloyl

chloride to a cooled solution of 3 in dry diethyl ether, in the presence of a slight excess of

a base scavenger (NEts), results in the formation of silylcarborane acrylate 19 and the

concomintant production of triethylammonium chloride. Following standard liquid-

liquid extraction procedure and recrystallization from hexanes 19 was obtained in good

yield as a colorless solid.

95

Figure 5.2 Components of the photopolymer solution (Formulation A)

To evaluate the etch resistance enhancement provided by the incorporation of the

silylcarborane acrylate monomer 19, two solutions were spun-cast from propylene glycol

methyl ethyl acetate (PGMEA) onto silicon wafers, cured under a UV lamp and etched

using oxygen plasma. The first formulation (A) was a conventional resist used for

nanoimprint lithography and served as a control (Figure 5.2). The second formulation

(B) was prepared by taking Formulation A and adding 10% by weight of 19. Figure 5.3

illustrates the difference in etch rate between the control formulation A, and the

carborane-containing counterpart formulation B. Assuming that both UV cured materials

are homogeneous along the direction perpendicular to the wafer and that the etch rates of

both materials are linear with respect to etching time, etch rates of approximately 268

nm/min for A and 163 nm/min for B were obtained. These results were obtained by

averaging the thicknesses measured by spectral reflectance of ten spots per cured sample.

96

600-

550-

500

450

400

350

300

250

200

150

100

50-1

0

Formulation AFormulation B (10% Carborane)

T ' I ' r00 02 04 06 08 1 0 1 2 1,4 1 6 1 8 20 2,2

Etch Time (min)

Figure 5.3 Determination of etch rates of the control formulation (A) and the

modified (B) resists.

Once the enhanced etch resistance was estabHshed, imprints were performed with

the two formulations. Table 5.1 combines the results obtained by profilometry in both

cases. Given that the same mask was utilized for A and B, it was expected to find similar

imprint depths and this finding suggests that the incorporation of the silylcarborane

acrylate does not dramatically affect the template filling dynamics of the resist precursor.

However, the drastic difference in feature depth after etching, here referred to as etch

depth, confirms the possibility to amplify features by means of incorporation of 19. The

amplification factor can better be appreciated by plotting the imprint depth and etch depth

in a bar chart (Figure 5.4).

97

Table 5.1 Imprint and etch profilometry results

Sample A Bimprint depth 55.41 56.91

etch depth 63.64 130.97

height change 8.23 74.06

(nm)

Amp Factor 1.15 2.30

% change 14.85% 130.14%

Depth Amplification

150.00

— 130.00

c

£ 110.00Q.<X)

T5

2i 90.00

^ 70.00

50.00

Figure 5.4 Bar chart for visual aid of depth ampliflcation from etch resists A and B.

Two patterns, small and large interdigitated electrodes, were imprinted onto the

resists to demonstrate visually the difference in depth amplification. The patterns were

imprinted and etched using an oxygen plasma reactive ion etch (RIE). Micrometric

features were chosen so as to facilitate the characterization of the imprints and all images

are taken at the point of break-through to the underlying wafer during RIE. In the case of

imprints realized with the conventional formulation A (Figure 5.5, i and iii), a brown film

can be observed indicating that the film covering the surface is relatively thin. In contrast,

a blue color can be observed when 19 is introduced (Figure 4, ii and iv). The blue color is

attributed to spectral reflectance due to constructive interference between the beams of

light reflecting from the surface of the film and the substrate. This coloration is an

98

imprint depth

cLch depth

A

additional qualitative confirmation of the efficacy of 19 to act as an etch resistant

additive.

Figure 5.5 Imprinted and etched device features. On the left are features patterned

into unmodified formulation A (i) and (iii), on the right are the same features

patterned into formulation B, (ii) and (iv).

This difference in resist thickness at break-through is critical as far as allowing

the patterns to be used successfully in a lithographic process. The patterns were coated

with gold by vacuum evaporation and a lift-off step was performed using methanol. After

metallization and lift-off, it can be clearly seen that the thickness of the features prepared

using formulation A were not tall enough to allow easy diffusion of the lift-off solvent

99

under the interdigitated features (Figure 5.6 and Scheme 5.2). However, in the case of

the ampHfied features prepared by means of incoprorating the carborane-modified resist

B, the lift-off easily resolves the interdigited lines.

Figure 5.6 Patterned gold features, (i) Unresolved interdigitated electrodes using

formulation A as an imprint layer (top) and (ii) using the B resist resolved patterns

are observed (bottom).

The difference in thickness at breakthrough actually originates from the difference

in etch resistance between the imprint layer and the lift-off layer. In the case of the

conventional formulation (A), both the imprint layer and the lift-off layer have

comparable etch resistance which translates into virtually no amplification of the patterns.

In contrast, the carborane containing formulation (B) is resistant enough to RIE to afford

an amplification of the interdigitated electrode pattern (Scheme 5.2).

100

Scheme 5.2 Comparative schematic illustrating the mechanism by which the

patterns are obtained. The brown layer represents the silicon wafer, the gray layer

is the imprint layer and the top layers are the two respective types of formulations.

Silylcarborane-containingConventional resist

resist

Unresolved

interdigitated

electrodes

Pattern

Amplification

Resolved

interdigitated

electrodes

5.4 Conclusion

A novel acrylate monomer 19 containing an inorganic boron cluster that is further

fiinctionalized with a silicon-containing group has been synthesized. Incorporation of

10% by weight of the silylcarborane acrylate 19 in formulation for UV-NIL showed a

significant improvement in the etch resistance of the imprint layer. Additionally, the etch

rates measured using an oxygen plasma were considerably decreased relative to a control

sample lacking both boron and silicon and lead to an amplification improvement of a

101

factor of two. The latter contributed to facilitating the lift-off step after metallization of

interdigitated electrode patterns. The utilization of inorganic cluster additives in resist

technology is a novel approach to the appliflcation of features in UV-NIL and we are

currently investigating the possibility to expand this methodology to other types of

inorganic cluster additives.

5.5 References

[I] M. F. Hawthorne, Angewandte Chemie, International Edition in English 1993,

950.



[3] J. F. Valliant, K. J. Guenther, A. S. King, P. Morel, P. Schaffer, O. O. Sogbein, K.

A. Stephenson, Coordination Chemistry Reviews 2002, 232, 173.

[4] D. M. Murphy, D. M. P. Mingos, J. M. Forward, Journal ofMaterials Chemistry

1993, 5, 67.

[5] C. A. Reed, Chemical Communications 2005, 1669.


2007, 2, 43.

[7] J. Dai, C. K. Ober, Proceedings of SPIE-The International Society for Optical

Engineering 2003, 5039, 1 1 64.

[8] J. Dai, C. K. Ober, Proceedings of SPIE-The International Society for Optical

Engineering 2004, 5376, 508.

[9] J. Dai, C. K. Ober, L. Wang, F. Cerrina, P. Nealey, Proceedings of SPIE-The

International Societyfor Optical Engineering 2002, 4690, 1 193.

[10] D. Bratton, D. Yang, J. Y. Dai, C. K. Ober, Polymers for Advanced Technologies

2006, 17, 94.

[II] B. D. Gates, Q. B. Xu, M. Stewart, D. Ryan, C. G. Willson, G. M. Whitesides,

Chemical Reviews 2005, 705, 1 1 71

.

[12] L. J. Guo, Journal ofPhysics D-Applied Physics 2004, i7, R123.

102

[13] P. R. Krauss, S. Y. Chou, Applied Physics Letters 1997, 77, 3 1 74.

[14] M. D. Stewart, C. G. Willson, Mrs Bulletin 2005, 30, 947.

[15] F. Palmieri, J. Adams, B. Long, W. Heath, P. Tsiartas, C. G. Willson, ACS Nano2007, /, 307.

[16] I. W. Moran, A. L. Briseno, L. S., K. R. Carter, Chemistry of Materials 2008, 20.

[17] K. Nakamatsu, K. Tone, S. Matsui, Japanese Journal ofApplied Physics Part l-

Regular Papers BriefCommunications & Review Papers 2005, 44, 8186.

[18] E. C. Hagberg, M. W. Hart, L. H. Cong, C. W. Allen, K. R. Carter, Journal ofInorganic and Organometallic Polymers and Materials 2007, 17, 377.

[19] L. J. Guo, Advanced Materials 2007, 19, 495.


[21] Y. C. Simon, C. Ohm, M. J. Zimny, E. B. Coughlin, Macromolecules 2007, 40,

5628.

103

CHAPTER 6

CONCLUSIONS AND RECOMMENDATIONS

This final Chapter comprises two parts. The first section provides an overview of

the work described in Chapters 2 through 5. In the second part, each Chapter is revisited

individually, providing an outline of future directions for the projects and suggesting

some possible project extensions based on preliminary data.

6.1 Dissertation Summary

The main goal of this work was to understand and overcome the challenges

associated with the incorporation of carboranes in polymeric architectures. In order to

realize the versatility of carborane-based inorganic-organic hybrid materials, novel

synthetic strategies have been developed allowing for the creation of unique functional

materials. This dissertation illustrates how the utilization of well-defined inorganic

clusters tethered to a polymerizable handle leads to novel hybrid materials that are easily

characterized and whose range of application is immense. Rather than focusing on one

particular application, the approach taken here was meant to open up new areas of studies

in the field of hybrid materials in general, and in the realm of carborane-containing

polymers in particular. This strategy has proven to be fruitful as it allowed for the

development of four distinct projects described in Chapters 2-5.

The present work complements previous studies on the incorporation of silicon

oxide frameworks in polymeric architectures.[l] The key to all chapters was the synthesis

of monofunctional carborane alcohol and its subsequent modifications to yield a

polymerizable moiety. This synthesis was achieved using silicon protecting groups by

104

improving the reliability of previously published protocols. [2] Although this was not the

emphasis of the present work, the presence of /erZ-butyldimethylsilyl protecting group

imparted some very important characteristics to the polymers. As will be discussed in

section 6.2.2, the presence of the silyl group seems to have an unforeseen role in the

ROMP of monomer 4 present in both Chapters 2 and 3. The presence of the bulky silyl

group was a very important part in the addition of sterically hindered side-chains

disrupting molecular packing (Chapter 4). In Chapter 5, the presence of a silyl group

contributed to the incorporation of etch resistant silicon in the resist formulation.

In Chapter 2, the first examples of amphiphilic diblock copolymers have been

described. In order to achieve this goal, a new oxanorbornene monomer was developed

and ROMP was chosen as a versatile method of polymerization. It is important to observe

that the reported work is only the second type of controlled blocky architectures

containing carboranes.. Two different approaches were utilized. The first route is based

on polycationic species obtained after acidic cleavage of a ?erf-butoxycarbonyl group.

The resulting ammonium provided the necessary water solubility to the second block and

offered a latent reactive site for the coupling of a rhodamine-B isothiocyanate dye and

attachment of PEG-groups by means of a Michael addition. Confocal microscopy

revealed the internalization of the labeled polymer inside the cells. Additionally, the

solution behavior of these polymer was monitored by dynamic light scattering and atomic

force microscopy and it was found that these polymers aggregate as spherical micelles in

aqueous solution.

The second approach (Chapter 2) is a somewhat more direct approach to the

introduction of PEG side chains into the polymer using a PEG norbomene ester. The

105

sequential addition of three monomers afforded a block copolymer that was further

labeled using nitrobenzoxadiazole. Both routes allowed for the synthesis of blocky

architectures with excellent control over the polydispersity of the resulting copolymers.

Chapter 3 is a direct extension of the polymerization studies done in Chapter 2.

The carborane-based oxanorbomene was copolymerized with cyclooctene to yield

polyethylene-like materials. Remarkable structural changes were observed as the polarity

of the reaction solvent was modified. Despite the crystallinity of monomer 4 and contrary

to what has been found in the case of silicon oxide nanoclusters, no crystallization was

observed, even when introducing flexibility into the chain by means of hydrogenation or

by increasing the loading of cyclooctene. As observed for other hybrid materials, the

thermal properties were improved by increasing the carborane loading.

While studying the crystallization behavior of SONIC-COE copolymers, the

potential to incorporate bulky silylcarborane pendant groups to give particular properties

to polyaromatic structures became apparent. In Chapter 4, the development of

silylcarborane-containing fluorene was achieved based on the reversal of connectivity of

alcohol 3 in two ways: a tosylation and a bromination using an Appel reaction. The latter

proved to be more efficient as the yields were significantly improved to obtain a

dibromofluorene with two bulky silylcarborane side chains. Using microwave-assisted

Yamamoto-coupling, it was observed that the molecular weights of homopolymers was

limited due to steric hindrance. Copolymers of dihexylfluorene and carborane-containing

monomer 17 were performed to circumvent this limitation. As anticipated, the

introduction of a monomer with less steric hindrance led to higher molecular weight

106

polymers. This finding was corroborated by the red-shift observed in solution indicating a

longer conjugation length.

Finally, in Chapter 5, a new silylcarborane acrylate has been synthesized and

incorporated in formulations for imprint lithography. With as little as 10% incorporation,

the modified resists showed significant improvement in etch resistance upon plasma

treatment, with amplification factors above two for the imprinted layers. The modified

formulation allowed for facile lift-off after metallization of interdigitated electrode

patterns.

As of 2003, only one published record of boron clusters in controlled polymeric

architectures existed. Since then, a strong push for carborane-containing polymers has

been witnessed, highlighting the relevance of the work described in this manuscript. [3 -8]

This dissertation opens up unique avenues for research in the field of carborane-based

polymeric architectures. The following section highlights some of the possible

continuations of the present work, some of which are already well underway. Due to the

different nature of each subject developed in Chapter 2-5, the recommendations made

here will follow the arrangement of the dissertation.

6.2 Future work

6.2.1 Materials for BNCT

In Chapter 2, novel carborane-based amphiphilic architectures have been

developed. One obvious extension of this work is evaluating the potential of these

materials as BNCT agents. Initial in vitro studies have shown the internalization of the

charged amphiphilic structures into human epithelial carcinoma cells. In order to identify

107

whether these types of architectures are viable alternatives to the current delivery

methods used in BNCT,[9] more thorough in vitro testing is needed. In particular, it will

be critical to find a way to assess the quantity of boron internalized by the diseased cells,

to investigate the chances of success for this approach. Another critical point that needs

to be addressed is the efficacy of these materials in intravenous deliveries. PEG chains

along the backbone of the polymers were specifically incorporated so as to improve the

pharmacokinetics of the polymeric drug. [10] The success of this strategy can only be

monitored by the use of animal models to evaluate the stealth nature of these systems.

The advantage of utilizing polymers in drug delivery stems from the possibility of

introducing a whole array of functionalities, such as markers or site-specific tags. In

particular, seminal work by Kiessling et al. has demonstrated the possibility to

polymerize gadolinium chelating norbomene moieties to serve as magnetic resonance

imaging contrast agents. [11] The copolymerization by ROMP of these markers with the

monomer designed in Chapter 2 will facilitate the implementation of in vivo testing of the

presented architectures. Additionally, one can also think of adding cancer-specific tags

such as cholesterol or folic acid, to specifically target the malignant tissues. [12, 13]

Finally, aUhough the utility of ROMP to synthesize controlled architectures for

drug delivery has been demonstrated, some questions still remain unanswered in terms of

the biocompatibility of these macromolecules. Another very interesting approach consists

in utilizing polyesters and click chemistry. The fact that polyesters can be easily

hydrolyzed in the body by enzymatic reactions makes them attractive biodegradable

delivery vehicles. Emrick et al. have demonstrated the usefulness of such strategies for

attachment of cationic polypeptides for gene delivery by click chemistry. [14] Based on

108

that work. Figure 6.1 illustrates a possible synthetic strategy to obtain water soluble

carborane-based polyesters.

b) NaNg

V

Figure 6.1 Synthetic strategy towards biodegradable BNCT agents

6.2.2 Influence of the silyl-protecting group and utilization in radiation shielding

applications

As discussed in Appendix B, the copolymers of cyclooctene and monomer 4 offer

numerous advantages in terms of composition which could make them excellent

candidates for radiation shielding applications. Therefore, initial simulation work needs

to be done to evaluate the shielding potential of these materials. In parallel, these

polymerization reactions need to be scaled up to evaluate the thermomechanical behavior

of the obtained structures. Mechanical integrity will play a major role in the use of

109

polymers as radiation protection. Although the chemistry shown here presents some

undeniable advantages in terms of multifunctionality, it is naive to believe that they will

solve all problems and an integrative engineering approach will probably be necessary to

incorporate these materials into functional radiation protection systems, such as space

suits or rovers.

Aside from these very practical considerations, the work presented here raises a

number of more fundamental questions, which are maybe even more interesting. In

particular, the observation that in the presence of amines at elevated temperatures the

silyl group has a tendency to cleave off the carborane cage might be an alternative

strategy for the synthesis of heterodifunctional carboranes. It is important to notice that in

both cases there is an available source of hydrogen in the reaction media: residual acid

from the ammonium in Chapter 2, /?t7ra-toluenesulfonylhydrazide in Chapter 3. Further

studies will have to determine whether this proton source plays a role in the cleavage of

the silyl protecting group. This information will in turn allow for the development of

novel protection-deprotection strategies that can be important in carborane chemistry.

Conversely, the discovery of the possibility to cleave the silyl group in the

presence of amines raised some additional questions regarding the importance of the silyl

group on the morphology and thermomechanical properties of the polymer. Attempts to

deprotect the hydrogenated polymers H-12(100) with TBAF (Figure 6.2) resulted in an

apparent drastic decrease in molecular weights (from 58,000 g/mol to 19,000 g/mol) with

no increase in polydispersity (1.13 to 1.10). These findings are very puzzling and deserve

to be further investigated to determine whether this decrease is due to secondary

interactions or simply due to the loss of the bulky TBDMS groups. The disappearance of

110

the silyl peaks in the NMR and the appearance of a new signal at 5.1 ppm confirmed that

the deprotection was efficient (Figure 6.3).

-I—I—I—I—I—1—I—1—I—1—I—1—I—1—I—1—I—1—I—I—|-

15 16 17 18 19 20 21 22 23 24 25

Elution Time (min)

Figure 6.2 Deprotection of the hydrogenated polySONIC H-12(100). Scheinatic(top)

and GPC chromatograms (bottom)

111

lUnv *° ^° 2°

Figure 6.3 'H NMR spectrum of H-21. * Solvent impurity

Alternative pathways involving the preliminary deprotection of the monomer

prior to polymerization proved really promising (Figure 6.4). Despite the apparent loss of

control illustrated by the observation of multimodal chormatograms in GPC, it was

observed that the resulting polymers had some remarkable thermal properties with an

onset of decomposition temperature of 353 °C, a char yield of 46% and a Tg of 200 °C.

These polymers seem to have a bright future in uses for high temperature applications.

Also, unlike polyaromatic imides they are very soluble in most organic solvents which

makes them very attractive candidates for a variety of engineering applications.

As mentioned above, the polymers obtained by homopolymerization of 20 lead to

multimodal polymers. It would be therefore very interesting to evaluate how carboranes

interfere with the polymerization process for example with in situ NMR monitoring.

Finally, the changes in alternation upon solvent change lead us to believe that the

polymerization sequence can be controlled between polar and apolar monomers by

changing the polarity of the medium Simple experiments including the addition of

112

triphenylphosphine should give us an insight into the factors governing the order of

addition of the monomers.

21

Figure 6.4 Alternative route to obtain deprotected carborane polymers.

ppm (f1)7.0 6.0 5.0 4.0 3.0 2.0 1.0

Figure 6.5 H NMR spectrum of monomer 20.

6.2.3 Polyfluorenes with carboranes in the backbone

The possibiUty to incorporate carboranes as pendant group shows some promising

applications notably in terms of neutron detection or simply to prevent intermolecular

stacking upon annealing of the molecules. Therefore, the utilization of these materials for

113

these applications needs to be investigated. Additionally, efforts to incorporate

carboranes in conjugated polyfluorenes will be a great complement to initial studies by

Vicente et al. on polythiophenes.[12] Several possibilities can be envisioned including

the incorporation of paracarborane moieties in the backbone. Some of these strategies are

depicted below.[15]

Figure 6.6 Synthesis of monomers incorporating carboranes along the backbone.

Sonigashira conditions: (Ph3P)2PdCl2, Cul, Et2NH

114

6.2.4 Novel high-boron content resists for EUV lithography and nanoimprint

lithography

The synthesis of a carborane-containing aerylate 19 opened the opportunity to

investigate novel material for imprint lithography. Previous work by Ober et al. had

highlighted the advantages of using carborane-containing resists for EUV lithography.

The advantage of the silyl functionalization approach is the incorporation of silicon

which enhances etch resistance. It seems therefore like adding even more silicon into the

matrix will lead to better materials for lithography in general and potential unique resists

for EUV lithography. Figures 6.7, 6.8 and 6.9 illustrate some progress that has been

achieved towards that goal. By incorporating a pentamethyldisilyl (PMDS) protecting

group, the etch resistance of the material is expected to be improved. Additionally, the

absence of any oxygen in the monomer makes these polymers particularly suitable for

EUV radiations as boron, carbon, silicon and hydrogen are all transparent at these

wavelengths. The Si-Si bond of the PMDS group might limit the possibility to

polymerize 23 by radical techniques but should still be suitable for anionic

polymerization. This will however require a level of purity that has not been achieved

yet.

115

116

(0(0 0 (O (O

r T'-j"I

" ~\\ 1 [--1- !

I

1 1 1

i

11 1 1

i^

'

1 1 1

i

'

\ r—I"'" T"

-9.0 -10.0 -11.0 -12.0 -13.0 -14.0 -15.0 -16.0

ppm (f1)

Figure 6.8 *H NMR spectrum of intermediate 22

6.3 Final word

The opportunities for research presented in section 6.2 are direct continuations of

the work described in this thesis. Nevertheless, the field of functional-carborane

containing polymers is still young and is, by no means, limited to these extensions. The

possibilities to functionalize carboranes to obtain "camouflaged" structures with various

electronic compositions, the idea of attaching these compounds to non-cytotoxic gold

nanoparticles or even the possibility to create non-linear optical materials are just a few

examples that should motivate researchers in developing carborane-based functional

polymeric architectures.

117

6.4 References

[I] L. Zheng, A. J. Waddon, R. J. Farris, E. B. Coughlin, Macromolecules 2002, 35,


[3] S. E. A. Gratton, M. C. Parrott, A. Adronov, Journal of Inorganic andOrganometallic Polymers and Materials 2005, 75, 469.


2007,2,43.


Symposia 2003, 196, 201.




[8] D. T. Welna, J. D. Bender, X. Wei, L. G. Sneddon, H. R. Allcock, Advanced

Materials (Weinheim, Federal Republic ofGermany) 2005, 77, 859.


Research 2005, 11, 3987.


[II] M. J. Allen, R. T. Raines, L. L. Kiessling, Journal of the American Chemical

Society 2006, 725, 6534.

[12] E. Hao, B. Fabre, F. R. Fronczek, M. G. H. Vicente, Chemistry ofMaterials 2007,

79,6195.

[13] D. Pan, J. L. Turner, K. L. Wooley, Chemical Communications 2003, 2400.

[14] B. Parrish, R. B. Breitenkamp, T. Emrick, Journal of the American Chemical

Society 2005, 727, 7404.

[15] M. A. Fox, J. A. K. Howard, J. A. H. MacBride, A. Mackinnon, K. Wade, Journal

ofOrganometallic Chemistry 2003, 680, 155.

118

APPENDIX A

BORON NEUTRON CAPTURE THERAPY AND ENHANCED PERMEABILITY

AND RETENTION

A.l Principles of Boron Neutron Capture Therapy (BNCT)

The figures regarding cancer and cancer progression reported by the world heahh

organization are appalling.[l] By the year 2020, the cancer rate will have increased by 50

% and currently, in numerous countries, the disease is responsible for the death of a

quarter of the population. In spite of all the efforts by oncologists, an effective treatment

minimizing noxious effects has yet to be developed, particularly for the incurable

varieties of the disease. Ideally, one can dream of a method that eradicates exclusively the

diseased cells and leaves the healthy ones intact. BNCT is a process that provides a smart

solution to address this problem.

In 1936, based on Taylor's observation of the aftermaths of the capture of a

neutron by a "^B atom, Locher developed the principles of a radiation-based cure meant

to target specifically malignant cells, and thus BNCT was bom.[2,3] It consists of a two

step process. In the first step, a harmless boron containing species is accumulated in the

tumor cell. In the second step, upon neutron irradiation, the capture of a thermal neutron

by '^B engenders the formation of an unstable ["B] isotope that instantly decays. The

subsequent energetic reaction products, the lithium nucleus (''Li^^) and the a-particle

("^He^"^), will trigger ionizing events in the close vicinity, ~10 microns, of the malignant

cell. [4] The astuteness of this method lays in the fact that there is a huge difference

between the thermal neutron capture section of boron (3837 barns) and that of the

119

elements commonly found in the human body (C, H, N, O) (1.8 bams at best for N).

Furthermore, thermal neutrons present a dependable inertness with these elements. This

binary method offers thus great advantages in terms of efficiency and selectivity, leaving

virtually intact the cells in which no boron has been accumulated. The rate of linear

energy transfer (LET) of the lethal particles, produced by the "^B(«,a)^Li reaction, is

indeed so high that their energy is dissipated in minute volumes, ideally concentrating on

the affected cells.

If they are theoretically appealing, the application of these concepts is somewhat

difficult. In the following section, some of the limitations will be explained starting with

the accumulation problems, which is the very reason for this study. It has been

acknowledged that the efficiency of the treatment is highly dependent on the amount of

boron accumulated within the tumor tissues. It is important to maximize the amount of

boron with respect to the abundant quantities of nitrogen and hydrogen in particular. The

latter two can indeed react with thermal neutrons through the 'V(«,p)''*C and 'H(«,y)^H

reactions. A rough estimate for the minimum quantity of '^B that must be present for

adequate capture ranges from 10 to 30 ^g per g of tumor. This minimum is obviously

governed by the location of the boron containing entity with respect to the malignant cell.

The medical consequence of neutron capture events is measured by the relative biological

effectiveness (RBE). The latter represents the effective noxiousness of resulting particles

or y-radiation from neutron capture reactions. The RBE is defined as the quotient

between the energy dose of a reference radiation creating a certain biological effect and

the energy input necessary for the physical particle or radiation to have the same

120

biological impact. The RBE of the products of BNCT is commonly approximated around

2.5.

Figure A.l Schematic of the elimination of diseased tissues using BNCT

Another concern with BNCT lays with the development of appropriate sources of

neutron. BNCT relies on the encounter of a thermal neutron with a '^B.[5] The use of

thermal neutrons for treatment of deeply rooted glioma is unreasonable as a consequence

of scattering by hydrogen atoms that does not allow sufficient penetration. Scientists have

resorted to the use epithermal neutrons sources which, without harming the patient

through hydrogen recoil, will supply the tumor cell with a dependable source of thermal

neutrons upon declaration by inelastic collisions with H atoms.

A.2 Enhanced Permeability and Retention (EPR)

Selectivity is an ideal that oncologist pursue tenaciously. Yet, the human body

does not facilitate their task for the mechanisms governing affected and healthy cells are

very similar. Conventional molecular approach fails to deliver curing agent to only

malignant cells. The vectors of well-known chemotherapy display insufficient selectivity

and have the tendency to be distributed at random in the patient's body, undermining the

efficacy of such treatment. Nonetheless, the propensity of tumor tissues to amass

121

macromolecular assemblies, known as the EPR effect, fosters hope and augurs for the

uniting of polymer therapeutics and cancer treatment. [6]

This unique feature of malignant tissues is attributed to concomitant effect of

anatomical and physiological mutations, such as the augmentation of the vascular density

emerging from the formation of new blood vessels, the paucity of smooth muscle layer

therein and the alteration of the lymphatic system's ability to recover (lack of

drainage). [7] The escape of macromolecules into the diseased tissues is facilitated by the

production of substances facilitating the creation of blood vessels (vascular endothelial

growth or permeability factors VEGFA/^PF) and the massive release of mediators. The

buildup of bioactive macromolecules in the tumor surpasses largely their concentration in

plasma by up to a factor of ten. and possibly increasing the accumulation of drugs up to

70-fold.

Bearing these physiological considerations in mind, both intra- and extracellular

deliveries have been envisioned. [8] In the former, the polymer-drug or polymer-protein is

internalized in the tumor cell by endocytosis and the active agent is then released through

a pH response or an enzymatic treatment. On the contrary, extracellular delivery rests on

the delivery of a polymeric material in the interstitial tumor tissues. Two avenues have

been contemplated in regards to extracellular delivery. On the one hand, extracellular

systems involving membrane activity and recognition features have been designed. On

the other hand, the coupling of a macromolecular assembly containing a drug and a

polymer enzyme that would interact outside of the cell to release the drug has also been

examined. It is important to recall that no cytospecific recognition (antibody, cell

receptor/ligand binding) is needed for the EPR to happen.

122

Normal lieajB

TuTXMjr tissue

AngogQfiic lumojrvsssels ars dsorganzedand leaky

vasaNir into •, > ;Qi:|

nomal tKeu9' îj[ j . Norm* ^selB âve

a tight endotfteiiim

/.î ritravenous injection

of poV^r therapeutic

Figure A.2 Schematic of the principles of the EPR effect (image from Ref. [8]).

Numerous systems (N-(2-hydroxypropyl) mathacrylamide-doxorubicin, styrene

maleic anhydride neocarzinostatin, etc.) and architecture (polymer-protein, micellar

entrapment, hyperbranched polymers) have been developed with encouraging results. [6-

8] A few conclusions have been drawn. Aside from the classical considerations

(hemolysis, cytotoxicity, etc), the macromolecular drug must be water-soluble and its

molecular weight must exceed 40 kDa to avoid renal excretion. Although polymeric

drugs can be neutral, it is commonly accepted that slightly charged systems show

stronger interactions with tumor tissues. Both negatively and positively charged have

their own advantages and thus, which is better is still a subject of debate. The former

123

offers longer plasma half-life and the beneficial absence of interaction with plasma

proteins. The latter facilitates the stabilization with the phosphate group of DNA

molecules as well as the interaction with the negatively charged membrane of tumor cells

for internalization. Further research is needed to determine which one is the most

efficient.

On another level, the release of the active agent as a whole poses a complicated

problem that is extremely hard to solve. Crafting linkages that are going to release the

drug at the right pH or upon action of a specific enzyme remains elusive. Therefore,

gaining control over the trigger is an integral component sought by researchers. To date,

they appear to have only looked at release methods where biological mechanisms are

involved.

In sum. researchers have had a hard time harnessing an effective trigger to release

active agents accumulated in tumor tissues by EPR. Conversely, they have not been able

to synthesize a carrier to efficiently bring boron containing molecules into the tumor

tissues for BNCT. Therefore, we propose to design a method in which biocompatible

carborane polymers will combine the natural accumulation of macromolecules described

as EPR effect and the ability of BNCT to produce cytotoxic particles in a controlled

fashion.

A.3 References

[1] World.Health.Organization, Vol. 2005, 2005.

[2] H. J. Taylor, Proceedings ofthe Physical Society, London 1935, 47, 873.

[3] G. L. Locher, American Journal ofRoentgenology. Radium Therapy 1936, 36, 1

.

[4] M. F. Hawthorne, Angew. Chem. Int. Ed Engl. 1993, 950.

124


Research 2005, 77,3987.

[6] Y. Matsumura, H. Maeda, Cancer Research 1986, 46. 6387.

[7] K. Greish, J. Fang, T. Inutsuka, A. Nagamitsu, H. Maeda, Clinical

Pharmacokinetics 2003, 42, 1089.


125

APPENDIX B

RADIATION SHIELDING

B.l Introduction to the Requirements of Space-Resistant Materials

The increased necessity for more protective space-survivable materials emerged

from the newly resumed global endeavor to further space exploration.[l] The prospects

of Lunar inhabitation, the maintenance and development of the international space station

(ISS), and interplanetary travel (including manned missions to Mars), foretell many

challenges that will require breakthroughs in terms of material science to withstand the

hostile environment of space. [2,3] Such innovations will include the development of

successful shielding of crew-members, rovers and other spacecrafts from the damaging

effects of galactic cosmic rays (GCRs) and solar energetic particles (SEPs).[4] Currently,

to prevent the harmful consequences resulting from exposure to radiation, regulation is

performed through duration control and access restriction.

In the history of space travel, radiation shielding has not always been a major

concern. The duration of the voyages was short enough that the adverse effects on the

astronauts was negligible. Instead, the mechanical behavior of the chosen material was

the principal concern. However, as the space community is preparing to launch a journey

to Mars, protection from radiation and particularly GCRs has become a key factor. Given

the longer duration, the need for materials capable of encompassing new crew safety

issues (e.g. radiation protection) and maintaining the functional capabilities (e.g.

mechanical behavior) of the one formerly used is more apparent. Wilson et al. have

considered the implementation of multifunctionality in space mission and report,

126

"utilizing multifunctional materials ... will improve safety and lower mission costs". [5]

Furthermore, it has been emphasized that a multidisciplinary optimization is essential for

choosing the future components of spacecrafts. Consequently, concomitant work at the

frontier of material science, synthesis and radiation shielding will assure the successful

development of muhifunctional materials. [6]

Guidelines for materials research stipulate that polymeric materials are more

suitable for radiation shielding than metal alloys. An ideal shield "maximizes the number

of electrons per unit mass, maximizes the nuclear reaction cross section per unit mass and

minimizes the production of secondary particles". [5] High hydrogen-content materials

meet these requirements and show good efficacy. For example, polyethylene (PE) is

presently being tested as a shielding material in the ISS to ensure crew safety. However,

it offers limited versatility. Finding alternative solutions offering multifunctionality and

efficient radiation shielding has yet to be achieved.

Unlike unpredictable SEPs and local radiations trapped in belts, GCRs are a

continuous source of radiation, and thus understanding what their consequences could be

is crucial to the design of new shielding materials. When GCRs hit and penetrate matter,

nuclear reactions occur, yielding different particles (e.g. neutrons) and radiations. Fast

neutrons (E > 10 keV) are emitted through spallation processes[7] and prove to have

deleterious effects on organisms. Through collisions with living tissue, they are likely to

cause the ionization of hydrogen atoms (hydrogen recoil reaction), creating severe

damage to the living organism. Accordingly, research for an adequate shield will have to

take this fact into account.

127

B.2 Rationale for the use of carboranes in neutron shielding.

The great neutron-capture cross sectional area of has already been employed

in various laboratory neutron-shielding applications as well as for medical

processes. [8] [9] The nuclear reaction happening upon irradiation of a carborane cage is

namely '°B(«,a)^Li. The combination of PE, which slows down the neutrons, and boron-

containing materials, capturing the subsequent low-energy neutrons, thus appears to be a

savvy strategy. The neutrons will hit the numerous hydrogen atoms along the polymer

backbone and bring them to an energy range where '^B has a wide enough cross-sectional

area to harvest them via the '°B(«,a)^Li reaction. In order to safeguard the crew from

harmful exposures, incorporating boron-containing materials, such as hybrid carborane

polymers, is an innovative solution. Besides, the use of '^B enriched compounds might

increase the efficacy of our products. Looking carefully into those materials from the

standpoint of radiation shielding and tailoring an appropriate structure based on the use of

carboranes is an exciting challenge that should be undertaken.

While it is convenient from a structural point of view to describe the materials

discussed in Chapter 3 as polyethylene-like, it is important to also point out some of the

similarities and differences that could exist between them. In particular, it is important to

point out that the description of polyethylene-like materials seems only really valid in the

context of the materials containing the smallest amount of carboranes. As the fraction of

carborane oxanorbomene increases the materials lose all resemblance to polyethylene.

This phenomenon can be illustrated as one compares the neat increase in glass transition

temperature as one starts to incorporate more and more SONIC in the structure.

128

As was observed in Chapter 3, the copolymers of SONIC and COE do not

crystallize, which not only indicates that the carborane cage do not pack in a way that

leads to the formation of inorganic crystalline layers but also demonstrates that the linear

polyethylene-like segments are too short to favor nucleation. In that sense, the materials

that contain the least amount of carborane can be assimilated to low-density or very low-

density linear polyethylene. In particular, it is very interesting to assimilate the pendant

carborane to the short-chain a-olefms that are used in the process of making these

materials. More mechanical testing would most certainly enable a better comparison of

these SONIC-COE copolymers with polyethylene materials and permit to determine

whether or not they can be described as polyethylene-like from an engineering

perspective. Nevertheless, since the present manuscript was written from a more

chemistry oriented standpoint, the similarities in structure between low-density linear

polyethylene and the hydrogenated copolymers with low volume fraction of carborane

favor this association.

129

— Qocmi-IG poKeAi Ls

Figure B.l Efficiency of blends of '^B and polyethylene and other materials for

neutron shielding (image from Ref.[10])

The advantage of the copolymerization approach in comparison with a blending

approach is clearly a better control over the the density of carboranes. Another formal

advantage of borated polymers stands in the back-scattering of electrons. A conventional

PE reflects a lot of electrons which could prove to be ill-fated for extravehicular activity.

On the contrary, the capture of neutrons by boron mitigates the amount of neutrons back-

scattered. This feature will be very beneficial for long repairs on spacecrafts.

B.3 References

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W. Atwell, R. Turner, G. Badhwar, Mercury, Mars and Saturn 2004, 33, 2204.

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J. R. Letaw, R. Silberberg, C. H. Tsao, Nature 1987, 330, 709.

J. W. Wilson, F. A. Cucinotta, M. H. Y. Kim, S. W., in 1st International

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C. S. Allen, R. Burnett, J. Charles, F. A. Cucinotta, R. Fullerton, J. R. Goodman,

A. D. Griffith Sr, J. J. Kosmo, M. Perchonok, J. Railsback, S. Rajulu, D. Stilwell,

G. Thomas, T. Tri, J. Joshi, R. Wheeler, M. Rudisill, J. W. Wilson, A. Mueller, A.

Simmons, NASA, 2003, p. 102.

Jean Chemin, Personal Communication, 2004.

G. L. Locher, American Journal ofRoentgenology. Radium Therapy 1936, 36, 1.

B. W. Robertson, S. Adenwalla, A. Harken, P. Welsch, J. I. Brand, P. A. Dowben,

J. P. Claassen, Applied Physics Letters 2002, 80, 3644.

R. C. J. Singleterry, S. A. Thibeault, Langley Research Center NASA, 2000.

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