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International School of Physics "Enrico Fermi" - Course CLXXVI
"Complex materials in physics and biology"
Varenna 29 June - 9 July 2010
Towards Complex MatterFrom Supramolecular Chemistry to
Adaptive Chemistry
Jean-Marie Lehn
13.7 billion yearsLife on Earth
Thought
PHYSICS CHEMISTRY BIOLOGY
Chemistry starts around here
thinking
living
InformationComplexity
Matter
?
EVOLUTION of the UNIVERSE
EVOLUTION towards COMPLEX MATTER
dividedcondensed
organized
Time
EVOLUTION of MATTER under the PRESSURE of INFORMATION
� How has matter become complex in the history of the universeup to the evolution of the biological world ?
� What higher forms of complex matter are here to be evolved,to be created ?
?
BASIC QUESTIONTHEHOW DOES MATTER BECOME COMPLEX from the elementary particle to the thinking organism
to be created ?
PHYSICS
CHEMISTRY
BIOLOGY
The BRIDGE towards COMPLEX MATTER
SELF-ORGANIZATION
THE PATH TOWARDS COMPLEX MATTER
DIVIDED – CONDENSED - ORGANIZED
LIVING – THINKING MATTER !
SELF-ORGANIZATION of NON-LIVING MOLECULAR MATTER
Electromagnetic forces operate selection on structural diversity
leading to the progressive complexification of matter from
the non-living to the living world under the pressure of information.
PREBIOTIC CHEMICAL EVOLUTION
the non-living to the living world under the pressure of information.
Chemical evolution through selection on structural diversity driven by
intra and intermolecular forces implementing molecular information.
GENERALIZATION of
DARWINIAN EVOLUTION
EMERGENCE of COMPLEX ENTITIES
SELF-ORGANIZATIONoperating on
RANDOM DIVERSITY RANDOM DIVERSITY
Structuration of molecular matter by the electromagnetic forces
generating and operating on random structural combinations
CHEMISTRY
The SCIENCE of the
STRUCTURE of NON-LIVINGSTRUCTURE
and
TRANSFORMATION
of NON-LIVINGand
LIVINGMATTER
MOLECULAR CHEMISTRY
Mastering the Organization of Molecular MatterBuilding highly complex molecules from atoms
linked by covalent bonds
From the ATOM to the MOLECULE
UREA
VITAMIN B12
O
MILESTONES inMOLECULAR CHEMISTRY
1828
1972(1976)
NH2H2N
Friedrich Wöhler
Robert WoodwardAlbert Eschenmoser
WHITE BLOOD CELL and PARTICLES of the HIV VIRUS
A CANCER CELL andTWO KILLER CELLS
TO
SUPRAMOLECULAR CHEMISTRY
Implementing the interactions between moleculesCHEMISTRY BEYOND THE MOLECULE
FROM
MOLECULAR CHEMISTRY
SUPRAMOLECULAR CHEMISTRY
CHEMISTRY BEYOND THE COVALENT BONDMastering the NON-COVALENT BOND
CHEMISTRY of the ENTITIES linked by INTERMOLECULAR INTERACTIONS
CHEMISTRY of SYSTEMS based on CHEMISTRY of SPECIES and INTERACTIONS
RECOGNITION, REACTIVITY and TRANSPORT(CATALYSIS)
INTERMOLECULAR INTERACTIONS
for SUPRAMOLECULAR CHEMISTRY
Electrostatic Interactions
Hydrogen Bonding
Donor-Acceptor Interactions
Van der Waals Forces
Metal Ion Coordination
+ Medium effects : solvophobic
CHEMISTRY
MOLECULAR SUPRAMOLECULARSELF-ASSEMBLY
SELF-ORGANIZATIONA
B
CD SUPERMOLECULE
S
RECEPTOR
UBSTRAT E
SYNTHESIS
covalentbonds
INTERACTION
intermolecularbonds
RECOGNITION
TRANSFORMATION
TRANSLOCATION
FUNCTIONALCOMPONENTS
SUPRAMOLECULARFUNCTIONAL
SYSTEMS
Polymolecularassemblies
MOLECULAR RECOGNITION
requires INTERACTION for BINDING
INFORMATION for SELECTING
geometricalgeometrical
interactionalDOUBLE COMPLEMENTARITY
“SCHLOSS und SCHLÜSSEL”LOCK and KEY
Emil FISCHER 1894
PREORGANIZATION
an INFORMATION SCIENCE
The SCIENCE of INFORMED MATTER
CHEMISTRY :
MOLECULAR STORAGE
SUPRAMOLECULAR PROCESSING
of INFORMATION
MOLECULAR RECOGNITION
The LOCK and the KEY
Li+
LithiumK+
PotassiumRb+
RubidiumCs+
CéNa+
Sodium
SPHERICAL SUBSTRATES The ALKALI METAL CATIONS
Selective Binding and Transport of Spherical Cations
Lithium Potassium Rubidium CéCesium
Sodium
A series of spherical species of single charge and increasing size
SPHERICAL MOLECULAR RECOGNITION
[2.2.2] CRYPTAND [2.2.2] CRYPTATE
MACROBICYCLIC CRYPTANDS and CRYPTATES
1968
Design of 3D Receptors for Spherical Cations Cations
Structures in the Crystal
1968
CRYPTANDS and CRYPTATES 1968
SPHERICAL RECOGNITION
Complementarity in Size and Shape between Cavity and Cation
SPHERICAL RECOGNITION
NH4+
TETRAHEDRAL SUBSTRATEThe AMMONIUM CATION
RECEPTOR with TETRAHEDRAL RECOGNITION SITE
TETRAHEDRAL MOLECULAR RECOGNITION
COMPLEMENTARITY in SHAPE, SIZE and INTERACTIONS
MACROPOLYCYCLIC STRUCTURES of MOLECULAR RECEPTORS
Macrocyclic Macrobicyclic
Cylindrical Macrotricyclic Spherical
ANION RECEPTORS
ANION COORDINATION CHEMISTRY
C7 C10
SUPRAMOLECULAR CATALYSIS
HYDROGEN TRANSFER
CO-CATALYSISPHOSPHORYL TRANSFER
THIOLYSIS of ACTIVATED ESTERS
3) Regeneration1) Recognition 2) Reaction
1) Substrate binding2) Structural selectivity for dipeptide esters3) Large rate accelerations (about 104)4) Saturation kinetics and competitive inhibition5) High chiral recognition (factor of about 80)
Enzyme Models
MOLECULAR and SUPRAMOLECULAR DEVICES
SUPRAMOLECULAR OPTICSSUPRAMOLECULAR OPTICS
SUPRAMOLECULAR ELECTRONICS
SUPRAMOLECULAR IONICS
PHOTONIC SUPRAMOLECULAR DEVICE
DoubleFonction
Light Collection Light Conversion
Processus : Absorption – Energy Transfer – EmissionA TE E
TE
A –ET – E Σ A
Europium Cryptate
A
Components : Collector
STRONG REDLUMINESCENCE
(ΣA) and emittor E
A
A
A
E
SUPRAMOLECULAR ELECTRONIC DEVICES
Electron Transfer Charge Separation
Molecular Wire Polarized Molecular Wire
D-PS-A Photodiode
Photoswitch
D A
Caropolyene D-A34 Å 34 Å
Caroviologene A-A
SELF-ORGANIZATION
Spontaneous but information-controlledgeneration of supramolecular architectures
via molecular recognition patterns
MOLECULAR RECOGNITION DIRECTED
Beyond Pre-organization
From Molecular Recognition
SUPRAMOLECULAR CHEMISTRY
SELF-ASSEMBLY of the TOBACCO MOSAIC VIRUS
From 2130 protein subunits + 1 molecule of viral RNA
PROGRAMMED CHEMICAL SYSTEMS
MOLECULAR PROGRAMME
SUPRAMOLECULAR OPERATION
PROCESSING viaINFORMATIONstored in the
COMPONENTS
STAGES of INFORMATION INPUT for SPECIES OUTPUT
RECOGNITION GROWTH TERMINATION
PROCESSING viaRECOGNITION ALGORITHM
defined by the INTERACTION PATTERN
INTERMOLECULAR INTERACTIONSfor
SUPRAMOLECULAR SELF-ORGANIZATION
Electrostatic Interactions
Hydrogen BondingHydrogen Bonding
Donor-Acceptor Interactions
Van der Waals Forces
Metal Ion Coordination
+ Medium effects : solvophobic
SELF-ORGANIZATION of METALLOSUPRAMOLECULAR ARCHITECTURES
BRICKS/COMPONENTS : MOLECULESBRICKS/COMPONENTS : MOLECULES
CONNECTIONS / CEMENT : METAL CATIONS
The metal cations process the molecular information in the ligand molecules through the coordination algorithm
SELF-ASSEMBLY of a TRINUCLEAR DOUBLE HELICAL METAL COMPLEX
N
N
O
N
N
O
Cu+
OO
N
NN
NCu+
TRINUCLEAR HELICATES
N
N
N
N
O
N
N
N
N
O
Cu+
Cu+N
N
O
N
N
O
N
NN
NCu+
Cu+
N
N
SELF-ASSEMBLY of a TRINUCLEAR TRIPLE HELICAL METAL COMPLEX
N
N
N
N
Ni2+
N
N
N
N
N
N
N
Ni2+
Ni2+
N
N
N
N
N
N
N
N
N
N
N
N
Ni2+
Ni2+
Ni 2+
N
N
N
N
N
N
N
N
N
N
N
Ni
Ni2+
RN
NN N
NN
SELF-ORGANIZATION of METALLOSUPRAMOLECULAR GRIDS
From Nitrogen Ligands with TRIDENTATE Subunits and Metal Cations of OCTAHEDRAL Coordination Geometry
[2x2] Grids
NN
N NN
N NR R
NN
NN
N NN
N NR R
NN N
R
NN
MULTI-LIGANDMULTI-NUCLEARMULTI-METALLIC
MULTIFUNCTIONALITY ARRAYS of ADDRESSABLE « ION DOTS »
Metal Cations
[2x2] GRID ARCHITECTURES
MULTI-FUNCTIONAL SUPRAMOLECULAR DEVICES
for
Supramolecular Electronics
MULTI-LIGANDMULTI-NUCLEARMULTI-METALLIC
Supramolecular Spintronics Spin CrossoverTriggered Processes
[2x2] [FeII4L4] Grid
Supramolecular Electronics Multiple Redox States[2x2] [CoII
4L4] Grid
Generation of EMERGING PROPERTIES through MULTIPLICITY
+ 4 MX2
metal salt
4N
N
N N
R
N
N
N
NN
N
NN
N
N
N
N
N
N
N
N
N
N
N
N
R
R
R
[2x2] Grids with Octahedrally Coordinated Metal Ions
4 4+
M = CoII, ZnII, NiII, CdII, CuII, PbII
[2x2] grid
RN
N
N
N NR
R = H, Me, Ph
Ditopic bis-terdentate ligand
Multilevel Supramolecular Electronic Species
Reduction of [Zn4L4](BF4)8
N
NN
N
N
N
N
N
N
N
N
Ligand :
DMF ,TBAPF6(0.1M),glassy carbon electrodeversus ferrocene, room temperature
« Clustering » of reduction wavesCOULOMB BLOCKADE
NN
N NN
N
Ph
N
NN
N
N
N
N
N
N
= Zn II
Multilevel Supramolecular Electronic Species
Reduction of[Co4L4](BF4)8
1
arbi
trar
y un
its
N
NN
N
N
N
N
N
N
Electrochemical
Ligand :-3 -2 -1 0
-1
arbi
trar
y un
its
E / V vs. ferrocene
DMF , TBAPF6 (0,1M), glassy carbone electrodeversus ferrocene, room temperature
NN
N NN
N
Ph
CO2Me CO2Me
N
NN
NN
N
N
N
N
N
N
N
= Co II
INTERNAL COMMUNICATION betweenthe LIGANDS within the GRID mediatedby the COBALT CENTERS
[2x2] [Fe4L4](ClO4)8 Grid :a multiple state
magnetic spin transition switch
Three triggersThree levels
N
NN
N
N
NN
N
N
N
N
N
N
N
N
N
N
N
N
N
R
R
R
R
Proton NMR spectroscopy
308 K
Angew.Chem.Int.Ed .2000,39,2504-2507
308 K
288 K
268 K
248 K
228 K
208 K
020406080 -20 ppmLSHS
Addressing the Metal Centers in a Supramolecular Electronic Species
TopographyCITS : Current Induced Tunneling Spectrsocopy
[CoII4L4](BF4)8The [2x2] Grid
X RayStructure
Conductance Transmission Probability
Lines of 1D ordered[CoII
4L4]8+ gridsLocal Resolution
of the CoII ions
on HOPG
Addressing the Metal Centers of a [2x2] Cobalt(II) GRID
HOMO of Co4 [2x2]
DFT Theory
Theory and Experiment
DFT CalculationsJ. Kortus
(MPI Stuttgart)
Electron extraction from the Co-centered HOMO
Upper row): 3D representation of DFT-calculated electron density maps within an energy window between EF and -0.55 eV and between EF and -1 eV .
(Lower row): Central section of the measured CITS maps .
Experiment
TOPOSELECTIVE and CHIROSELECTIVE SELF-ASSEMBLY of HETERO-METALLIC [2x2] GRIDS
Achiral if
+
R R+
CHIRAL SELECTION in SELF-ASSEMBLY « Coupe de Roi »
RuII
FeII
Cl-
Achiral if
Chiral if
CHIRAL « CORNER » COMPONENTS
R R
S S
+
+or
[Ru2Fe2] GRID
SELF-ORGANIZATION of a [4x4] PbII16 GRID Array
from 24 components : 8 Ligand Molecules and 16 Lead(II) Cations
Single operationMultiple « hidden » steps
N
N
N
S
N
N
SN
N N NN N N
N N NN N
N N NN N N
N N NN N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
II
The Pb(II) CENTERS « ION DOTS »
N
N
N
N
N
N
N
N
S
S
SN
N N N
NN N N
N N NN N N
N N
NN N N
N N NN N N
N N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
(P b II)
83 MHz 207Pb NMR Spectra of the [4x4] PbII16 GRID
NANO-CYLINDERS : CYLINDRICAL NANOSTRUCTURES
3-Dimensional
NanosizePolymetallic
Nanosize
CylindricalArrays
by
MULTICOMPONENT SELF-ORGANIZATION
from two different types of ligands
N NN
RR
R
N
N
N
N
4 3+12 Cu++
N
N
N
N
Me
N
N
N
Me
N
N
N
N
Me
NN
NNN
N
NN
NNN
N
12+
4 3+ 12 Cu+
12+
Multilevel/Multicell Metallosupramolecular NANOCYLINDER
NN
N
RR
R
N
N
R =
N
N
4 3+12 Cu+
N
N
N
N
Me
N
N
N
N
N
Me
N
N
N
N
N
Me
NN
NNN
N
NN
NNN
N
4 3
R =
C6H5 substituents omitted
NANOCYLINDER
SELF-ORGANIZEDfrom3 LINEAR LIGAND
MOLECULES4 PLANAR LIGAND4 PLANAR LIGAND
MOLECULES12 METAL CATIONS
Cu(I)
N
N
NN
NN
N NN
N
N
NMe
Me
Me
9+
N
N
NN
NN
N NN
N
Me
Me
Me 6 +
N
N
N
N
Me
N
N
N
Me
N
N
N
Me
N
NN
N
NN
N
NN
N
NN
12+
11 15 19COMPOMENTS of THREE TYPES
SELF-ORGANIZATION of MULTICOMPARTMENTAL NANOCYLINDERS from
N
N
N
NN
NN
N NN
N
N
N
N
N
NN
NN
N NN
N
N
N
MeMe
Me
NN N
N
N
N
NN
NN
N NN
N
N
N
N
MeMe
Me
N
N
N
N
N
Me
N
N
N
N
N
N
Me
N
N
N
N
N
Me
NN
N
NN
NNN
N
N
NN
N
NN
4 +8 + 48
NNNN
NNN NNN
OONN N N
O O
MULTIPLE EXPRESSION of MOLECULAR INFORMATION
Double SubroutineProcess
Metal Cation CoordinationAlgorithms
SINGLE CODE SEVERAL OUTPUTSProcessing of the Same Molecular Information through Different Interaction Algorithms
MULTI-SUBROUTINE SELF-ORGANIZATION
linear combination cross-over
= pentacoordinate ion : Cu(II)= hexacoordinated ion : Fe(II), Co(II), Ni(II), Cu(II)
= tetracoordinated ion : Cu(I) = tetracoordinate ion : Cu(I)
Algorithms
N NO
NN
NNN
N
NN
N
N
O
N N
N
N
NN
O
N
N
O
N
N
O
N
N
O
O
N
N
N
N
N
O
NN
NNO
N N
O
N
N
ON
NNN
N
N
N
N
N
O
O
N
N
O
N
N
O
O
N
N
N
N
N
N
O
O
NO
N
N
N
N
O
N
N
O
N
N N
N
N
O
N N
N
N
Solid State Molecular Structure
= pentacoordinated ion Cu(II) = tetracoordinated ion Cu(I)
= hexacoordinated ion : Fe(II), Co(II), Ni(II), Cu(II)
N N O
O N N NN N N
NNO
N
N
N
N N O
O N N NN N N
NN
O
O
O
N
N
N
N
O
N
N
O N
N
N
N
N
N
N N
N
NN
1
NN
N NN
N
R
NN
N NN
N N
R R
NN
NN
N NN
N N
R R
NN N
R
NN
Are these representations the correct shapes of the free ligands ?
NO !R R R
N N N
N
STRONG CONFORMATIONAL PREFERENCE of 2,2’-BIPYRIDINE for the TRANSOID FORM
25 kJ/Molcisoid transoid
INDUCES HELICAL FOLDING of the Molecular Strands
N
N
N N
N
N N
N
N N
N
N N
N
N N
N
R R R R R R
N
6 subunits ligand strand
HELICAL FOLDING of a HETEROCYCLIC MOLECULAR STRAND
R
N NN
N
N
NNNN
NN
NN
N
NN
NN
R
RR
R
R
R = SnPrSolid State Molecular Structure
FOLDING CODONS
FOLDING CONTROLthrough
MOLECULAR SELF-ORGANIZATION through
through
STRUCTURE ENFORCING SUBUNITS Sequences of Aromatic Heterocylic Groups
Induction of Superstructures by Intramolecular Self-Organisation
of Oligoheterocyclic Strand
Conversion of the β-turn/helicity inducing form of the free pym-py / hyz-pymligand fragments into an extended linear shape upon binding of a metal ion
N
N
N
NN
N
N NN N
+
-
FOLDING / UNFOLDING INTERCONVERSION
transoid-transoid conformationcisoid-cisoid conformation
UNFOLDING by ION BINDING
Conversion of a linear ligand fragment py-py / hyz-pyinto a β-turn/helicity inducing form upon binding of a metal cation
N
N
N
NN
N +
-transoid-transoid conformation
FOLDING by ION BINDING
cisoid-cisoid conformation
transoid-transoid conformationcisoid-cisoid conformation
5 subunits ligand strand
MOTIONAL DYNAMIC DEVICES
IONIC MODULATION of EXTENSION/CONTRACTION MOTION
HELICAL STRAND UNFOLDING by ION BINDING
9 subunits ligand strand
5 subunits ligand strand
REVERSIBLE IONIC MODULATION ofHELICAL STRAND / LINEAR COMPLEX INTERCONVERSION
by COUPLING with a COMPETING CRYPTANT LIGAND
HELICAL STRAND UNFOLDING by ION BINDING
Generation ofEXTENSION / CONTRACTION MOLECULAR MOTION
Fueled by ACID / BASE NEUTRALIZATION ENERGY
MODULATION of COILING / UNCOILINGION-COUPLED / pH-INDUCED STRUCTURAL SWITCHING
Sequence of Triggering Agents
NANOMECHANICAL DEVICES
MOLECULAR
SUPRAMOLECULAR
MOTIONAL DYNAMIC DEVICES
Molecular/Supramolecular Entities undergoingMolecular/Supramolecular Entities undergoing
Triggered Molecular/Supramolecular MOTIONS
Reversible/Oriented Structural Changes
Triggered by External Effectors
CONTROLLED NANOMECHANICAL MOTIONSbetween ORGANIZED STRUCTURES
Generation of
PROGRAMMED SELF-ORGANIZATION
Spontaneous but controlled generation of
supramolecular architectures
NANOSCIENCE and NANOTECHNOLOGY
well-definedlargecomplex supramolecular architectures
A powerful alternative or complement to
NANOFABRICATION and NANOMANIPULATION
complexorganizedfunctional
From FABRICATION to SELF-FABRICATIONThe Ultimate Fabrication !
There’s even more room at the top !
COMPLEXITYthe goal is
There’s plenty of room at the bottom !
Richard Feynman
BEYONDNANOSCIENCE
andNANOTECHNOLOGY
SELF-ORGANIZATION
by DESIGN
INFORMATION
by DESIGN
INFORMATION DIVERSITY
with SELECTION
INFORMATIONPROGRAMMATION
INFORMATIONPROGRAMMATION
DIVERSITYDYNAMICS
ADAPTATION
N
N
N
N
N
N
N
N
O
N
N
N
N
O
Cu+
Cu+
N
N
N
N
Ni2+
N
N
N
N
Ni2+
N
N
N
N
+
SELF-RECOGNITION in HELICATE SELF-ASSEMBLY
N
N
N
O
N
N
N
N
N
O
Cu+
N
N
Ni2+
N
N
N
Ni2+
N
N
N
O
N
N
N
O
Cu+N
N
N
N
Ni2+
N
N
Krämer, R., Lehn, J.-M., Marquis-Rigault, A.,(1993) Proc. Natl. Acad. Sci. USA, 90, 5394
N
N
N
O
Cu+
N
N
N
N
N
N
N
O
Ni2+
N
N
N
N
Dynamic Combinatorial Library of Helical Metal Complexes
Dynamic Library of Circular Helicates
SO42-
N
n n+ + + + n-mer
Cl-
N
N
N
N
N
N N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N NN NNN
F e2+
NNNN N N
F e2+
F e2+
F e2+
F e2+
F e2+
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N N
N NNN
F e2+
F e2+
F e2+ F e2+
F e2+
N
N
N
N
NN
Cl-N
N
N
N
N
N
Hasenknopf, B. Lehn, J.-M., Kneisel, B.O., Baum, G. Fenske,D.Angew.Chem. Int. Ed. 1996, 35, 1838
+ FeX2
SUPRAMOLECULAR CHEMISTRY is a
DYNAMIC CHEMISTRY
due to the LABILITY / REVERSIBILITY ofdue to the LABILITY / REVERSIBILITY ofNON-COVALENT INTERACTIONS
enabling CONSTITUTIONAL VARIATIONthrough exchange, incorporation and decorporation
of the molecular components of a supramolecular entity
IMPORT DYNAMICS into
MOLECULAR CHEMISTRY
through REVERSIBLE COVALENT BONDS
DYNAMIC COVALENT CHEMISTRY
CONSTITUTIONAL DYNAMIC CHEMISTRYBOTH MOLECULAR / COVALENT and
SUPRAMOLECULAR / NON-COVALENT
DYNAMIC COVALENT CHEMISTRY
Dynamic Modification of the Constitution of Chemical Entities
CONSTITUTIONAL DYNAMIC CHEMISTRY
CDC
MOLECULAR SUPRAMOLECULAR
From
SUPRAMOLECULAR CHEMISTRY
To
DYNAMIC CHEMISTRY
� MOTIONAL Molecular MotionsNanomechanical Shape Changes, Motors
� REACTIONAL Dynamics of Chemical Reactions
CONSTITUTIONAL
Nanomechanical Shape Changes, Motors
Dynamic Modification of the Constitutionof Chemical Entities
CONSTITUTIONAL DYNAMIC CHEMISTRY
SUPRAMOLECULARand MOLECULARgenerates DYNAMIC DIVERSITY
enables the operation of SELECTION
CONSTITUTIONAL DYNAMIC CHEMISTRY
search for BIOLOGICALLY ACTIVE SUBTANCES
self-organization of DYNAMIC NANOSTRUCTURES
development of molecular and supramolecularCONSTITUTIONAL DYNAMIC ASSEMBLIES and MATERIALS
THE KEY for THE LOCK
DESIGNED CHEMISTRY
COMBINATORIAL CHEMISTRY
ONLY ONE KEY : THE RIGHT ONE
MANY DIFFERENT KEYS,
FIND
Search for BIOLOGICALLY ACTIVE SUBTANCES
COMBINATORIAL CHEMISTRY
DYNAMIC COMBINATORIAL/ COVALENT CHEMISTRY
DCC
MANY DIFFERENT KEYS,ALL MUST BE TRIED ;ONE OF THEM CAN BE THERIGHT ONE
FRAGMENTS OF KEYS INCONTINUOUS REARRANGEMENT,ONE OF THE COMBINATIONS, THE BEST ONE, IS SELECTED BY THE LOCK
Components
ConstituentsVIRTUAL / DYNAMICCOMBINATORIAL
LIBRARY
CONSTITUENTEXPRESSION
Librarygeneration
Library of interchanging
Dynamic Search for BIOLOGICALLY ACTIVE SUBSTANCESMOLECULAR RECOGNITION driven COMPONENT SELECTION
The Lock assembles
the KeyComponents
Lock/Key
Library of interchangingspecies
Initial buildingblocks
the Key
Selection of the best binder
Components
ConstituentsCONSTITUENTEXPRESSION
Librarygeneration
Library of interchanging
Dynamic Search for BIOLOGICALLY ACTIVE SUBSTANCESMOLECULAR RECOGNITION driven COMPONENT SELECTION
Selection of the best binder
VIRTUAL / DYNAMICCOMBINATORIAL
LIBRARY
Components
Lock/Key
Selection by the receptor/lock of the thermodynamically preferred constituent among all thepossible combinations/constituents forming the dynamic combinatorial library
Library of interchangingspecies
Initial buildingblocks
The Lock assembles
Its Key
REVERSIBLE REACTIONS
AMINE – CARBONYL CONDENSATIONS
implementing
DYNAMIC COVALENT CHEMISTRY DCC
Imine
� organic and biological groups
� compatible with aqueous phase
� kinetics controllable by pH
Acylhydrazone
CARBONIC ANHYDRASE Active Site & Inhibitor
CO2 +H2O H2CO3
K = 1.1 nMKd = 1.1 nM
A DYNAMIC LIBRARY of IMINES
equilibrateequilibrate
I. Huc & J.-M. Lehn, Proc.Natl.Acad.Sci.USA 1997, 94, 2106
Kd = 1.1 nM
In absence of Carbonic Anhydrase :
EFFECT of CARBONIC ANHYDRASE on LIBRARY COMPOSITION
« DYNAMIC SCREENING »
CA active site
Time (min)
Time (min)
1 eqof CA
No CA
In presence of Carbonic Anhydrase :EXPRESSION / AMPLIFICATIONof the LIBRARY CONSTITUENT CLOSEST to the BEST INHIBITOR
In absence of Carbonic Anhydrase :ratio about 1/1 of these two constituentsof the dynamic library
Tetrameric CONCANAVALIN A (Con A) complexed with Trimannoside
J. H. Naismith, R. A. Field J. Biol. Chem. (1996) 271, 972
Concanavalin A Trimannoside Binding Site
Components of a Dynamic Combinatorial LibraryDirected towards Concanavalin A
1
2
3
B
C
G
4
5
6
A D
E
F
H
I
Potential generation of 690 constituents
1.0
Dynamic Deconvolutionof the Concanavalin A Combinatorial Library
Blk CL 1 2 3 4 5 6 A B C D E F G H I
0.0
0.5
MULTI-COMPONENT SELF-ASSEMBLY of [2x2] GRID ARCHITECTURES from LIGAND SUBUNITS
N O-O3S
O
SO3-O
DYNAMIC NANOSTRUCTURES
SO3-
-O3S
N NN
N OO3S
O Ph
N NN
N O
O Ph
N
N
N
N
O
Ph
N
N
N
N
O
Ph
so3-
2
OH
NH3+
OO
Co(II) or Zn(II)
H2O
SO3-
SO3-
-O3S
SO3-
O
N
O
N N
Ph
OO
CO2-
HO
CO2- M2+
NaHCO3
H O
N NN
N
-O2C
O-O2C
O Ph
-O2C
N
N
CO2-O
Ph
N
N
N
CO2-O
Ph
M2+
NaHCO3
DYNAMIC SELECTION of LIGAND COMPONENTSDRIVEN by FORMATION of a [2x2] GRID COMPLEX
Dynamic Library of Imines
NH3+
SO3-
NH3+
OMe NH3+
SO3-
OH
NH3+
NH3+
SO3-
H2O
M2+ = Mn, Fe, Co, Ni, Cu, Zn
N NN
N O-O2C
O Ph
N
N
CO2-O
Ph N
N
CO2-O
H2O
M = Mn, Fe, Co,Ni, Cu, Zn
COMPONENTSELECTION
DIVERSITYGENERATION
CONSTITUTIONAL DYNAMIC MATERIALSMOLECULAR SUPRAMOLECULAR
DYNAMERS : Dynamic Polymers
POLYMERIC MATERIALS exhibiting REVERSIBLE
COMPONENT EXCHANGE
SUPRAMOLECULAR / NON-COVALENTMOLECULAR / COVALENT
BIODYNAMERSDynamic Analogs of Biopolymers
DYNAMERS : Dynamic Polymers
SUPRAMOLECULAR POLYMER CHEMISTRY
SUPRAMOLECULAR / NON-COVALENT DYNAMERS
The chemistry of SUPRAMOLECULAR POLYMERS
entities generated by
POLYASSOCIATION of
COMPLEMENTARY MOLECULAR MONOMERS
through NON-COVALENT INTERACTIONS
DYNAMIC POLYMERS
controlled by MOLECULAR RECOGNITION PROCESSES
SUPRAMOLECULAR LIQUID CRYSTALLINE POLYMERS
HN
NH
O
O
O* * O
O
OR
OR
O
NH
HN O
O
TP2 TU2
from CHIRAL COMPLEMENTARY H-BONDING MOLECULAR COMPONENTS
DA
D
AD
AN
HN
HN O
OO *
O
*RO
OR N
NH
NHO
O
OO
O
O
SUPRAMOLECULAR / NON-COVALENT DYNAMERS
Advanced Materials, 1990, 2, 254 Z= CH3 R= C12H25
Z
O Z
OO
O
HN
NH
O
O
O * * OO
OR
OR
O
NH
HN O
O N
HN
HN O
Z
OZ
OO *
O
*OR
OR N
NH
NHO
Z
O Z
OO
O
HN
NH
O
O * * OO
OR
OR
O
NH
HN O
O
O
TP2 TU2
(TP2,TU2)n
N
HN
NH O
Z
Z
OO
*O
*OR
OR N
NH
NHOO
Tartaric acid spacer T = L, D, M
L-L D-D M-M
Helical Textures formed by the LU2-LP2 , DU2-DP2 and MU2-MP2 strandsobserved by electron microscopy
MAIN-CHAIN SUPRAMOLECULAR POLYMERformed via SEXTUPLE HYDROGEN BONDING
between Molecular Monomers bearing Complementary Recognition Groups
n
O
OO
NO
H
N
N
N
O
NN
H
H
H
O
C3H7
OC3H7
NO
H
NN
NON
N
H
H
H
OH7C3
OH7C3
N
O
H NNN
O
N
N
H
H
H
OC3H7
O
C3H7
Cross-linkingMonomer
+
STM Image of a Supramolecular Polymeric Chain
at the graphite-solution interface
1eqO
NHO
NHO
N
N
NH
NH
C9H19O
C9H19O
O
HNO
HNO
N
N
HN
HN
C9H19
O
C9H19O
A
Current: 20 pABias : 300 mV
a = 2.51 nm b = 4.04 nmA = 5.94 nm2/dimerα = 35.8°
2.5 eq
HN
NH
N
O
O O
O
O
O
O
O
O
N NH
HN
O
O OB
A + B 6 µmol solution in 1,2,4 trichlorobenzene
MOLECULAR / COVALENT DYNAMERS
DYNAMIC POLYMERS generated by POLYCONDENSATION of FUNCTIONAL COMPLEMENTARY MONOMERS through
REVERSIBLE COVALENT CONNECTIONS
OHC CHO H2N NH2N N
dialdehyde dihydrazide polyacylhydrazones
OHC CHOO
HN NH2O
NHH2N O
HN NO
NHN
n
dialdehyde diamine polyimines
2 2
n
PolyimineDYNAMER FILM
Water-desintegrative film based on a Dynamer containing imine groups
( 20 cm x 60 m x 30 µ )
2 tons dynamer prepared
T. Nobori et al.,Mitsui Chemicals, 2006
Toward « GREEN » PLASTICS !
POLY ACYL HYDRAZONES
MOLECULAR / COVALENT DYNAMERS
NO
XN
NH
OY
O
NH
N
REVERSIBILITY
AMIDE
IMINE
BIOPOLYMERS MATERIALS
DYNAMICBIOPOLYMERSBIODYNAMERS
Dynamic PeptoidsREVERSIBLE POLYAMIDES
DYNAMICPOLYAMIDES
Hn
H REVERSIBILITY
HYDOGENBONDING
Silicone-derived Covalent Dynamer : DYNASIL
Very Soft Stretchy Film n
+
H2O
OSi
OSi
OSi
O
HNH2N
O
NNH2
HSi OHC
OSi
OSiSi O CHOO
OSi
OSi
OSi
O
HNN
O
NN
HO O
SiO
SiSi O CH
Si
Very Soft Stretchy Film n
Developed by Takashi Ono, Shunsuke FUJII, Mitsui Chemicals Inc.
Very Soft Stretchy Film Hard Monomers
CC
DDn
BBAA
OHC
MeO
OO
O
OMe
CHO
OONN
H2N NH2
OO
H H
OSi
OSi
OSi
O
HNN
O
NN
HO O
SiO
SiSi O CH
Si
Soft-to-Hard Transformation of the Mechanical Properties of a Polyacylhydrazone Covalent Dynamer by Incorporation of Monomers
MECHANO DYNAMIC POLYMERS
25mol% 50mol%Soft Stretchy Film 75mol%
AA AADDCCBB AA DDBBCC
DDAA AABB AABBAA AA
BB BB60°, 24h, in CHCl3
Conversion of a Soft Stretchy Film into a Hard Tough Film by Dynamic Modification
Exchange reaction through the interface of two different dynamic polymers
smart optical materials responsive to external stimuli
color fluorescence
Color and fluorescence changes of dynamic polymersinduced by bond recombination and component exchange
OPTO DYNAMIC POLYMERS
two dynamic polymer filmsare superimposed
heated in oven
color fluorescence
color and fluorescence changedonly where superimposed
A-B
A’-B’
A-B
A’-B’
A-B
A’-B’
A-B’A’-B
A-B’A’-B
Concept :introducing a difference in degree of conjugation by bond recombination
extended local conjugationno conjugation
POLYMERS
no conjugation
exchangereaction
NN
CH
CH
NN N
NCH
S CH
NN
C
NN
CH
CH
NN
CO O
weak local conjugation
C
NN
CH
S CH
NN
CO O
AB
A’B’
A’B
AB’
The two polymer films are cutwith scissors and superimposed
heated at 170C under 365nm
Color Fluorescence
Can we draw a picture using dynamic polymers ? Oui ! bien sur !
for 5min
Both polymer films are formed using a mixed solvent (CHCl3/DMF).Both films are soft and relatively stretchy containing 9-10wt% of DMF.
under 365nm
yellow coloronly where superimposed
yellow-green fluorescenceonly where superimposed
smart optical materials responsive to external stimuli
Reversible Diels-Alder Reactions
between FULVENES and CYANOOLEFINS
CO2R''NC
R''O2C CN
CNCO2R''
CN
R'
R
25oC
CDCl3
R'
+
R25°C
at ROOM TEMPERATURE
Dicyanofumarates
Alkyl Tricyanoethylenecarboxylates
Self-Contained Dynamic Processes
R''O2C CNCO2R''
CN
CO2R''NC
NC CN
CNCO2R''
CNCN
R'
R
25oCCDCl3
R'
+
R 25°C
NC
CN
NC
O
O O
O
NC
CN
CNO
O
O
On
m+1 + m
Formation of a Diels-Alder Dynamer
O
O
O
On
CNCN
NCNC
CNNC
O
OO
O
NCNC
CNCN
NC CN
O
OO
Om
Self-Healing of Diels-Alder Dynamer Films
99
Opening of the adducts and chain motion Formation of new adducts across the interface
Possible Self-Healing Mechanism
ADAPTATIONthrough
DYNAMIC CONSTITUTIONAL VARIATIONby COMPONENT SELECTION
in response to
environment / mediumenvironment / mediumphase changephysical effectorchemical effectormorphological change / switching
in a CONSTITUTIONAL DYNAMIC NETWORKSet of CONNECTED INTERCONVERTING CONSTITUENTS
Structures of the Monomers
HG = (CH2CH2O)6OMeFlexible hydrophilic side-chain
Rigid hydrophobic core
Formation of polymeric rod-like nanostructures in aqueous solution
AMPHIPHILIC DYNAMERS
Poly(CA-CH)
unfoldedPoly(CA-CH)
folded helical nanotube
The reversible polycondensation of amphiphilic di(acylhydrazine) and di(aldehyde) monomers gives a dynamic acylhydrazone copolymer, which adopts a helical folded structure to minimize the exposure of hydrophobic surface area (HG groups omitted for clarity).
Rigid Rod (SANS)Mw about 300 kD
hydrophobiccore
Competitive Polymerization Uncovers Monomer Component Selectivity
CONSTITUTIONAL ADAPTATION to the ENVIRONMENT Hydrophobically-Driven Monomer Selection in Dynamers
R = (CH CH O) OMe
CA
CH
O
O
NH
HN
N
N
NR
NR
O O
O ONH
H2NNH
NH2
BHOR
NH
NH2
O
NH
H2NO
BHOR
NH
NH2
O
NH
H2NO
Rigid hydrophobic core
H2O
Selective polymerization of CH over BH
in 5 mM aqueous phosphate, 55 °C[CA]0 = [CH]0 = [BH]0 = 4.6 mM
R = (CH2CH2O)6OMe CHPoly(CA-CH)
NR
H
n
NRFlexible hydrophilic side-chain
in H2O / CH3CNSelectivity decreases on addition
of organic solvent, acetonitrile,to near random at 80% acetonitrile
ADAPTIVE SELF-ASSEMBLY
Constitutional Dynamic ProcessCH3-NO2
ADAPTATION to the ENVIRONMENT
Solvent Modulated Reversible Interconversion between Two Self-Assembled Nano-Architectures
CH3-CN
CONSTITUTIONAL DYNAMIC NETWORKSNetworks of DYNAMICALLY INTERCONVERTING CONSTITUENTSconnected either structurally (molecular and supramolecular arrays)
or reactionally (sets of connected reactions or interactions)
Towards COMPLEX SYSTEMS
PHYSICALLY or CHEMICALLY MODULATED
AGONISTICConnectivity
ANTAGONISTICConnectivity
System of Four Constituents AC, AD, BC, BD
from Recombination of four Components A,B,C,D
two by two A and B with C and D
AC AD
BC BD
NN
N
O
N
N
OHO
HO
OHN
NH2
H
HH
N
N
N
O
N NO
OH OH
O
HN
NH2
H
H
H
NN
N
O
N
N
H
H
H
NN
O
O
H
pH 4- 7
Na+, K+, NH4+O
OHOH
NH
N
O
N
N NH2O
NH
H2N
SELF-ORGANIZATION DRIVEN COMPONENT SELECTIONin a SUPRAMOLECULAR G-QUARTET based HYDROGEL
formed by Guanosine 5’-Hydrazide
Model of the G-quartets [G4-K+] aggregates
TEM picture Gel in sodium acetate buffer at 15 mM at pH 6
15 mM22 0 C
N N
OOH
OH
O
NH
H2N
N NNO
OHOH
O
NH
H2NH
H
Dynamic Decoration of the G-quartet
NN
N
O
N
N
OHO
HO
OHN
NH2
H H
N
N
N
O
N NO
OH OH
O
HN
NH2
H
H
H
N
HH
NN
N
O
N
N
OHO
HO
OHN
N
H H
N
N
N
O
N NO
OH OH
O
HN
NH
H
H
N
HH
R
R
M++ +
-
R-CHO
O
NH
N
O
N
N NH2O
H2N
DOUBLE DYNAMIC SOL / GEL SYSTEM
Supramolecular / non-covalent dynamics Molecular / covalent dynamics
Formation of a SOL or a GEL depending on the residueattached at 15 mM concentration
HH
NN
N
O
N
N
OOH
OH
ONH
H2N
HH
N
N
N
O
NNO
OHOH
O
NH
H2NH
H
H
HN
N
N
O
N
N
OOH
OH
ONH
N
HH
N
N
N
O
NNO
OHOH
O
NH
NH
H
H
R
R
M+- - R-CHO
N
HO O P O
OH
OH
SO3NaSO3Na
O
NaO3S
NaO3SR =
Sol Sol Gel Gel
O
OHOH
NH
H2N
Dynamic Covalent / Combinatorial Library
N
O
O P O
OH
OH
O
SO3NaAcHN
OH
O
NH
NH2
AcHN
O
NH
N
pD 6
1:1:1:1
ACAD
AcHN
O
NH
NH2
SO3Na
AcHN
O
NHN
HO
NAcHN
O
NHN
O
PHO OH
O
HO
NAcHN
O
NHN
HO
A
B
C
D
Statistical distribution
NO SELECTIONas there is no gel formationwith these constituents
OHSO3NaOH
BC15 mM each in 0.5 M sodium acetate buffer BD
OH
O
PHO OH
O
AD AC BD BC
15
17
19
21
23
25
B D
Self-Organization-driven Dynamic Component Selection through Gel Formation
N
O
HOO P O
O H
O H
O
SO3NaAcHN
OH
O
NH
NH2
SO3Na
AcHN
OH
O
NHN
pD 6
1:1:1:1
BD
HN
N N
N
O
OHOH
O
H2NO
NH
N
SO3Na
AD
O
OHOH
NH
N
O
N
N NH2O
NH
H2N
NN
N
O
N
N
OHO
HO
OHN
N
H
H
H
N
N
N
O
N NO
OH OH
O
HN
NH
H
H
NN
N
O
N
N
OOH
OH
ONH
H
HH
N
N
N
O
NNO
OHOH
O
NH
NH
H
H
R
R
R
15 mM each in 0.5 sodium acetate buffer
A
B
C
D
Amplification of constituent B leading to formation of a stronger gel
8% 39% 42% 11%
N. Sreenivasachary and J.-M. Lehn. Proc. Natl. Acad. Sci. USA. 2005, 102, 5938-5943.
SELECTION under SELF-ORGANIZATION PRESSURE
HO
NAcHN
OH
O
NHN
BD
BC
B15 mM each in 0.5 M sodium acetate buffer
O
N
HOP
OH
OH
OR =
NH
N
RGel
O
P OHHO
O
B,C = agonistsB antagonist to A and D
GELAC
AD AC BD BC
0
10
20
30
40
8% 39% 42% 11%
Signifigance for PREBIOTIC EVOLUTION of MATTER
CONSTITUTIONAL DYNAMIC NETWORKSNetworks of DYNAMICALLY INTERCONVERTING CONSTITUENTSconnected either structurally (molecular and supramolecular arrays)
or reactionally (sets of connected reactions or interactions)
Towards COMPLEX SYSTEMS
PHYSICALLY or CHEMICALLY MODULATED
AGONISTICConnectivity
ANTAGONISTICConnectivity
System of Four Constituents AC, AD, BC, BD
from Recombination of four Components A,B,C,D
two by two A and B with C and D
AC AD
BC BD
AD AC BD BC
15
17
19
21
23
25
AD AC BD
0
10
20
30
40
CONSTITUTIONAL DYNAMIC NETWORKSPHYSICALLY or CHEMICALLY MODULATED
Statistical Distribution Enforced Distribution
Organized PhaseGel formation
Inorganized Sate Organized State
EffectorOrganization
AD AC BD BCAC, BD = agonistsAC, BD antagonists to AD and BC
AD AC BD BC
AC
BD
AD
BC
AC
BD
AD
BCAGONISTICConnectivity
ANTAGONISTICConnectivity
ADAPTATIONSELF-ORGANIZATION
SELECTIONdriven by
AMPLIFICATION of AC / BD
CONSTITUTIONAL DYNAMIC CHEMISTRY
CONSTITUTIONAL DYNAMIC MATERIALSDYNAMATS
MOLECULAR SUPRAMOLECULAR
DYNAMATS
ADAPTIVE TECHNOLOGIES
ADAPTIVE MATERIALS
CONSTITUTIONAL DYNAMIC CHEMISTRY
MOLECULAR
SUPRAMOLECULAR
DYNAMIC CONSTITUTIONAL DIVERSITY
� chemical systems undergoing continuous
recomposition/recombination/reorganization deconstruction/reconstruction
Novel Paradigm: SELECTION through
Dynamic Constitutional Diversity responding to the pressure of internal/external factors
externalfactors / stimuli
� through constitutional variation
ADAPTATION
� responding under the pressure of internal
MOLECULARCHEMISTRY
CONSTITUTIONALDYNAMIC ADAPTIVE
CHEMISTRY
SELF-ORGANISATION
DESIGN SELECTIONDIVERSITY
GENERATION
DYNAMICS
SUPRAMOLECULARCHEMISTRY
DYNAMICCHEMISTRY CHEMISTRY
DYNAMICS
ADAPTIVEEVOLUTIVE CHEMISTRY
DARWINIAN !
Towards
Steps towards COMPLEX MATTER
DESCRIBETHE PROCESSES THAT
LED TO
SELF-ORGANIZATION
UNDERSTANDLED TO
OCCUR IN
CREATE NOVEL
FORMS/EXPRESSIONS OF COMPLEXMATTER
ORGANIZED – LIVING – THINKING MATTER !
