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									HIGHLIGHT                                                                          www.rsc.org/csr | Chemical Society Reviews



From supramolecular chemistry towards
constitutional dynamic chemistry and
adaptive chemistry
Jean-Marie Lehn{
DOI: 10.1039/b616752g

Supramolecular chemistry has developed over the last forty years as chemistry
beyond the molecule. Starting with the investigation of the basis of molecular
recognition, it has explored the implementation of molecular information in the
programming of chemical systems towards self-organisation processes, that may
occur either on the basis of design or with selection of their components.
Supramolecular entities are by nature constitutionally dynamic by virtue of the
lability of non-covalent interactions. Importing such features into molecular
chemistry, through the introduction of reversible bonds into molecules, leads to
the emergence of a constitutional dynamic chemistry, covering both the
molecular and supramolecular levels. It considers chemical objects and systems
capable of responding to external solicitations by modification of their
constitution through component exchange or reorganisation. It thus opens the
way towards an adaptive and evolutive chemistry, a further step towards the
chemistry of complex matter.

Tracing the birth of a scientific area has     the identification of the roots are usually   forty years is presented in a perceptive
quite some arbitrary character. The            subject to scrutiny only once the tree        editorial.2
moment when the seed was planted and           has grown. This holds also for supra-            The concepts and the perspectives of
                                               molecular chemistry and for the present       supramolecular chemistry have been
                                               ‘‘Anniversary’’. In fact, the horizon has     delineated.3 The area has experienced
                             ´
Institut de Science et d’Ingenierie
Supramoleculaires, Universite Louis Pasteur-
          ´                    ´               broadened progressively as the landscape      an extraordinary development at the
                           ´
CNRS UMR 7006, 8 Allee Gaspard Monge,          has been revealed, from selectivity, to       triple meeting point of chemistry with
F-67000 Strasbourg, France.                    molecular recognition to supramolecular       biology and physics. It has given rise to
E-mail: lehn@isis.u-strasbg.fr;                chemistry. The path followed by the
Fax: (+33)390245140                                                                          numerous review articles, special issues
{ Dedicated to the memory of Professor Guy     present author has been briefly outlined      of journals and books.4–6 Recognising
Ourisson, mentor, researcher, teacher.         earlier.1 A reflection on these first         that it is impossible and illusory to
                                                                                             render justice to this intense activity,
                                                                                             this special Anniversary Issue assembles
                                  Jean-Marie Lehn was born in Rosheim, France in             expert presentations of some of the active
                                  1939. In 1970 he became Professor of Chemistry at the      areas of research in supramolecular
                                           ´
                                  Universite Louis Pasteur in Strasbourg and since 1979      chemistry.
                                                                         `
                                  he has been Professor at the College de France in             The intention here is just to briefly
                                  Paris. He shared the Nobel Prize in Chemistry in 1987
                                                                                             provide what could be considered as a
                                  for his studies on the chemical basis of ‘‘molecular
                                                                                             sort of blue print, emphasising however
                                  recognition’’ (i.e. the way in which a receptor molecule
                                  recognizes and selectively binds a substrate), which       the more recent developments, as pursued
                                  also plays a fundamental role in biological processes.     especially in our laboratory, together
                                  Over the years his work led to the definition of a new     with an outlook, along and beyond the
                                  field of chemistry, which he has proposed calling          lines of earlier horizons (Fig. 1).3,7–9
                                  ‘‘supramolecular chemistry’’ as it deals with the
                                  complex entities formed by the association of two or
                                  more chemical species held together by non-covalent
                                                                                             From molecular recognition
                                  intermolecular forces, whereas molecular chemistry         and information to
       Jean-Marie Lehn
                                  concerns the entities constructed from atoms linked        self-organisation
by covalent bonds. Subsequently, the area developed into the chemistry of
"self-organization" processes and more recently into "constitutional dynamic chemistry".     Molecular chemistry has, over about
Author of more than 700 scientific publications, Lehn is a member of many academies          two centuries, developed a wide range
and institutions. He has received numerous international honours and awards.                 of very powerful procedures for creating

This journal is ß The Royal Society of Chemistry 2007                                        Chem. Soc. Rev., 2007, 36, 151–160 | 151
                                                                                            From self-organisation by
                                                                                            design to self-organisation
                                                                                            with selection
                                                                                            Self-organisation is the fundamental
                                                                                            process that has led to the generation of
                                                                                            complex matter, from particles to the
                                                                                            thinking organism, in the course of the
                                                                                            evolution of the universe. Unravelling
                                                                                            the mechanisms of the self-organisation
Fig. 1 From Molecular, to Supramolecular and to Constitutional Dynamic Chemistry under      of matter offers a most challenging task
Preorganisation and Self-organisation by design and with selection.                         to chemistry.7 Along the way, as progress
                                                                                            is being made, implementation in non-
ever more sophisticated molecules and         tracing the path from merely condensed        natural, abiotic chemical systems may be
materials from atoms linked by covalent       matter to more and more highly orga-          performed.
bonds.                                        nised matter, towards systems of increas-        The spontaneous but controlled
   Beyond molecular chemistry, supra-         ing complexity.                               generation of complex supramolecular
molecular chemistry aims at constructing         Supramolecular chemistry has thus          entities by means of suitable components
highly complex, functional chemical           paved the way towards apprehending            and interactions amounts to performing
systems from components held together         chemistry also as an information science.     self-organisation by design.
by intermolecular forces.                     It started and developed as the chemistry        Self-organisation processes may be
   Numerous molecular receptors cap-          of the entities generated via intermole-      directed via the molecular information
able of selectively binding specific sub-     cular non-covalent interactions. By the       stored in the covalent framework of
strates via non-covalent interactions         appropriate manipulation of these inter-      the components and read out at the
have been developed. They perform             actions, it became progressively the          supramolecular level through specific
molecular recognition which rests on          chemistry of molecular information,           interaction/recognition patterns, that
the molecular information stored in the       involving the storage of information at       define processing algorithms. They thus
interacting species. Suitably function-       the molecular level, in the structural        represent the operation of programmed
alised receptors may effect supra-            features, and its retrieval, transfer, pro-   chemical systems,3,19,20 and are of major
molecular     catalysis   and     selective   cessing at the supramolecular level,          interest for supramolecular science and
transport processes.                          through molecular recognition processes       engineering.
   The control provided by recognition        operating via specific spatial relation-         They give access to advanced func-
processes allows the development of           ships and interaction patterns (hydrogen      tional supramolecular materials, such as
functional molecular and supramolecular       bonding arrays, sequences of donor and        supramolecular polymers,27–30 liquid
devices, defined as structurally organised    acceptor groups, metal ion coordination       crystals and lipid vesicles31–33 as well as
and functionally integrated systems           units, etc.).                                 solid-state assemblies.34,35
built from suitably designed molecular           Furthermore, in addition to this infor-       The design of molecular information
components performing a given action          mation sensing on direct intermolecular       controlled, ‘‘programmed’’ self-organis-
(e.g. photoactive, electroactive, ionoac-     contact, the investigation of selective       ing systems provides an original
tive, etc.) and endowed with the struc-       substrate (ions, molecules) transport         approach to nanoscience and nano-
tural features required for assembly          through membranes has allowed the             technology. In particular, the generation
into an organised supramolecular archi-       exploration of signalisation at a distance,   of well-defined, functional supra-
tecture. Thus emerged the areas of            through the generation of ionic or            molecular architectures of nanometric
supramolecular photonics, electronics,        molecular fluxes.                             size through self-organisation represents
ionics …3,5,10–18                                Achieving optimal molecular recogni-       a means of performing programmed
   A most basic and far-reaching con-         tion rests on the derivation of               engineering and processing of nano-
tribution of supramolecular chemistry to      receptor–substrate pairs presenting com-      materials. Technologies resorting to self-
chemical sciences has been the imple-         plementarity in geometry and interac-         organisation processes are in principle
mentation of the concept of molecular         tions, through correct construction of        able to provide a powerful complement
information and its corollaries, instruc-     one (or both) of the interacting species.     and/or alternative to nanofabrication
tions and programmed chemical systems,        Beyond mastering such preorganisation         and nanomanipulation procedures by
with the aim of gaining progressive           and taking advantage of it, supra-            making use of the spontaneous but
control over the organisation of              molecular chemistry has been actively         controlled generation of the desired
matter, over its spatial (structural) and     exploring the design of systems under-        superstructures and devices from suit-
temporal (dynamical) features. It led         going self-organisation, i.e. systems         ably instructed and functional building
to the ever clearer perception, deeper        capable of spontaneously generating           blocks. The long-range goal is to shift
analysis and more deliberate application      well-defined, organised supramolecular        from entities that need to be made to
of information features in the elabora-       architectures by self-assembly from their     entities that make themselves, i.e. from
tion and transformation of matter,            components.3,7,19–26                          fabrication to self-fabrication.

152 | Chem. Soc. Rev., 2007, 36, 151–160                                      This journal is ß The Royal Society of Chemistry 2007
                                                  that was always implicit and operating in   soft matter (polymer chains, colloids,
                                                  all processes investigated, but has been    etc.),43 morphological dynamics invol-
                                                  explicitly taken advantage of and imple-    ving changes in molecular shape; they
                                                  mented only in more recent years.           also cover the intriguing systems present-
                                                  Indeed, supramolecular chemistry is         ing ‘‘molecular machine’’ and oriented
                                                  intrinsically a dynamic chemistry in view   motion properties.44–48
                                                  of the lability of the non-covalent            Both aspects apply to supramolecular
                                                  interactions connecting the molecular       entities as well as to molecules. A third
                                                  components of a supramolecular entity.      novel type of dynamic processes is
                                                  The resulting ability of supramolecular     now to be considered, that opens wide
                                                  species to reversibly dissociate and        perspectives. It consists in:
Fig. 2 Schematic representation of the self-      associate, deconstruct and reconstruct         – constitutional dynamics, whereby a
assembly of metallosupramolecular [2 6 2],        allows them to incorporate, decorporate     chemical entity, be it as well molecular
[3 6 3] and [4 6 4] grid-type architectures       and rearrange their molecular compo-        as supramolecular, undergoes continuous
from ligand strands possessing respectively       nents. This dynamic character is            change in its constitution through
2, 3 and 4 complexation subunits. Subunits        essential as the supramolecular entities    dissociation into various components
containing either 2 or 3 binding sites (e.g. N
                                                  are synthesised or, better, synthesize      and reconstitution into the same entity
sites) correspond respectively to metal ions of
                                                  themselves by self-assembly from their      or into different ones.
tetrahedral and octahedral coordination.
                                                  molecular components through more or           The emergence of this third type of
                                                  less rapid exploration of the structure/    dynamic chemistry may be related to
   A great variety of (functional) supra-         energy hypersurface. It is thus at the      the explicit recognition of the dynamic
molecular architectures have been                 basis of the generation of the highly       features characteristic of supramolecular
generated by complex self-assembly pro-           complex architectures held together         entities and their introduction into
cedures, of purely ‘‘organic’’ as well as         by hydrogen bonding, donor–acceptor         molecules. Importing such dynamic fea-
of ‘‘inorganic’’ nature.3,5,21–26,36–39 The       interactions or metal ion coordination,     tures into molecular chemistry requires
latter have led to a range of metallo-            reported by numerous laboratories. It       shifting from static to ‘‘dynamic’’ cova-
supramolecular entities presenting origi-         also allows for self-organisation with      lent bonds, so as to endow molecular
nal physical and chemical properties, as          selection and gives to supramolecular       species with the ability to undergo
is the case for the grid-type arrays of           systems the ability to adapt their archi-   similar dynamic exchange and reorgani-
ligands and metal ions extensively inves-         tecture as well as their constitution       sation processes by virtue of the
tigated in the author’s laboratory                in response to factors such as the          reversible formation and breaking of
(Fig. 2).40                                       interaction with external entities, for     covalent connections. It implies looking
   As the self-organisation of supramole-         instance, in the generation of circular     at molecules as labile entities, in
cular entities takes place through pro-           helicates of different size depending on    contrast to the usual longing for
gressive build up of the final entities, it       the anion present in the environment        stability, and opens novel perspectives
has to explore the hypersurface of all            (Fig. 3).42                                 to covalent chemistry. It requires
available structure/energy combinations.             The next step consists in the recogni-   searching for reversible reactions and
Consequently, self-organisation pro-              tion that molecular chemistry is also       catalysts that allow the making and
cesses are in principle able to select the        endowed with similar dynamic features,      breaking of covalent bonds, preferably
correct molecular components for the              provided the molecular entity contains      under mild conditions. Whereas the
generation of a given supramolecular              covalent bonds that may form and break      supramolecular entities are dynamic by
entity from a collection of building              reversibly, so as to allow a continuous     nature, the molecular entities are
blocks. Self-organisation may thus take           change in constitution by reorganisation    dynamic by intent.
place with selection, by virtue of a              and exchange of building blocks. Thus,         This radical change in outlook
basic feature inherent in supramolecular          as an outgrowth of supramolecular           amounts to taking a standpoint opposite
chemistry, its dynamic character.                 chemistry, it leads to a Constitutional     to the traditional one and to consider
                                                  Dynamic Chemistry7,8,30 (CDC) on both       that the dynamic character, resulting
From supramolecular                               the molecular and supramolecular levels.    from reversible connections, rather than
chemistry to constitutional                          Dynamic chemistry may be generally       being a drawback gives access both to the
                                                  understood as encompassing two broad        richness of constitutional diversity and to
dynamic chemistry
                                                  areas:                                      the benefits of adaptability. It stresses the
Supramolecular chemistry has, from the               – reactional dynamics, concerning the    virtues of instructed mixtures,3 such as
start, been defined in its structural and         kinetics and mechanisms of chemical         was revealed in the self-selection pro-
bonding features as ‘‘chemistry beyond            reactions;                                  cesses in the side-by-side self-assembly of
the molecule’’, its entities being con-              – motional dynamics, concerning exter-   helicates in mixtures of ligands and metal
stituted of molecular components held             nal reorientations (such as overall         ions.49 It is this work that led us in the
together by non-covalent interac-                 molecular motions in liquids), internal     early 1990s to envisage a dynamic
tions.1,3,41 The third feature defining its       motions (such as rotations around           chemistry bringing into play the consti-
essence, resides in its dynamic nature,           bonds or site inversions), dynamics in      tution of chemical species.

This journal is ß The Royal Society of Chemistry 2007                                         Chem. Soc. Rev., 2007, 36, 151–160 | 153
Fig. 3 Dynamic (virtual) library of circular helicates generated from a tritopic ligand strand and octahedrally-coordinating metal ions, expressing
different constituents depending on the counter ion (chloride or sulfate) present.42


   In the context of the evolution of             interactional groups (supramolecular,             physically dynamic, based on physical
chemistry from molecular to supramole-            non-covalent, physical, interactional             non-covalent interactions.
cular, it represents a sort of ‘‘back to the      recognition). They may thus be con-                 As at both levels the processes may
future’’ step, going back to molecular            sidered either as chemically dynamic,             involve component recombination, they
chemistry to endow (provide) it with              involving chemical reactions or as                define a dynamic combinatorial chemistry
novel perspectives by introducing into it
and fertilising it with supramolecular-
type dynamic features.
   An intriguing line of development of
chemistry is thus being fuelled by a basic
paradigm shift from a constitutionally
static chemistry to a constitutionally
dynamic chemistry (CDC),7,8,30 encom-
passing both covalent molecular and non-
covalent supramolecular entities,9,50–55
defining respectively a dynamic covalent
chemistry (DCC) and a dynamic non-
covalent chemistry (Fig. 4). The forma-
tion and dynamic character of these
entities result respectively from reversible
condensation of components through
complementary functional groups (mole-
cular, covalent, chemical, functional
recognition) and from recognition-                Fig. 4 Constitutional dynamic chemistry (CDC) covers both dynamic molecular chemistry
directed reversible association of                and supramolecular chemistry that involve respectively dynamic covalent (dynamic covalent
components through complementary                  chemistry, DCC) and non-covalent connections.


154 | Chem. Soc. Rev., 2007, 36, 151–160                                            This journal is ß The Royal Society of Chemistry 2007
of supramolecular as well as of molecular     Implementation of CDC                         preferential formation of specific ligand
nature.50,53 This denomination stresses                                                     molecules and/or induces reversible
their combinatorial character, whereas        The basic feature of CDC is its dynamic       changes in them. Such processes may be
CDC highlights the fact that they             character that allows for the generation      traced back to early work on coordina-
concern the basic feature of chemical         of constitutional molecular and supra-        tion reactions of imine-based ligands,
entities, their constitution.                 molecular diversity on which to operate       that may now be revisited in the light of
   Constitutional dynamics imply changes      selection in response to the pressure         constitutional dynamics, but were not
in constitution concerning the nature,        of chemical or physical internal or           perceived as such at that time.61
number and arrangement of the com-            external factors, thus enabling adaptive         Self-organisation with selection occurs
ponents of molecular or supramolecular        chemistry.                                    in the metal cation driven build-up of the
entities, thus generating molecular and          Implementation of CDC may be con-          ligand that allows the generation of a
supramolecular diversity through con-         sidered from three points of view:            [2 6 2] grid-type metallosupramolecular
tinuous recomposition, recombination,            – the exploration of synthetic systems     architecture by selection of the proper
reorganisation, construction and decon-       directed at revealing the basic features      components from a virtual DCL
struction by either external (incor-          of CDC;                                       (Fig. 6).62 The addition of ZnII cations
poration, decorporation, exchange of             – the application to the search for        to a CDL of helical ligands drives the
components) or internal (rearrangement,       bioactive substances;                         system towards the expression of a
reshuffling of components) processes,            – the development of dynamic               [2 6 2] grid-type complex (Fig. 7).63 An
under the pressure of internal factors        materials.                                    intriguing case of self-sensing is found in
or external environmental stimuli. The           1) Numerous studies have been per-         the ZnII cation-induced rearrangement of
system may respond to such effects by         formed on either the substrate-assisted       a polyimine towards the polymer that,
expressing the constituent(s) presenting      moulding of molecular receptors for           once formed, generates a strong fluores-
best adaptation to a given situation,         substrates or the receptor-assisted casting   cence signalling the presence of the very
through selection of the most suitable        of substrates for receptors from dynamic      species, the ZnII cations, that have led to
components among those available.             combinatorial libraries (DCLs).50–53          its formation (Fig. 8).64 In these three
   A set of interconverting supramole-        Work in our group has been directed           cases the evolution of the system is driven
cular or molecular entities represents a      in particular towards the influence of        by cation coordination pressure.
real or virtual30,56 constitutional dynamic   physical and chemical effectors on the           CDC allows for ‘‘double dynamic’’
library (CDL). It may modify its com-         behaviour of DCLs, as for instance in         processes, that combine and take advant-
position, i.e. the relative amounts of its    the case of the constitutional dynamic        age of both non-covalent and covalent
constituents, and be characterised by         reorganisation exerted by temperature         dynamics, as in the assembling of
three main features:57                        and protonation on imine libraries57 or       metallo-architectures bearing functional
   1) conversion, the total amount of         the induction of liquid crystal properties    groups,62,65 or for performing constitu-
constituents generated with respect to        by an electric field acting on a dynamic      tional dynamic synthesis (CDS). In the
the free components;                          library.58                                    latter case, supramolecular dynamics
   2) composition, the distribution or           On the other hand, in the formation of     enable the assembly of functional com-
relative amounts of the different con-        guanine quartet-based hydrogels, it was       ponents with suitable selection and struc-
stituents, that also represents the selec-    shown that the system selected the com-       tural control, whereas molecular covalent
tivity of the system;                         ponents that generated the most stable        dynamics operate in post-assembly
   3) expression of a given constituent,      gel (Fig. 5).59 Such a self-optimisation      connection between the assembled com-
that may be defined as the product of         behaviour may be of broader significance,     ponents, resulting in molecular architec-
conversion and selectivity.                   namely for prebiotic chemical evolution,      tures of high complexity, as described in
   The simultaneous modulation of these       whereby selection is driven by phase          the formation of interlocked structures
three parameters of a CDL results in          cohesion, the entity selected being that      from metal-coordination66 or donor–
the expression of different constituents,     giving the most stable organised supra-       acceptor interaction67 directed assembly
through component selection driven by         molecular assembly in a sort of prebiotic     combined with imine formation.
chemical and/or physical stimuli. Such is,    Darwinism driven by self-organisation.           2) The search for bioactive substances
for instance, the case for sets of imine      The supramolecular organisation drives        amounts to searching for a molecular key
constituents, under changes in protona-       the selection of the components giving the    for a biological lock.50–53 Apart from the
tion and/or temperature.57                    ‘‘fittest’’ constituent.60                    random screening of natural or synthetic
   Changes in expression of the different        Chemical evolution occurs through          compounds, two ‘‘classical’’ approaches
constituents as a factor of external para-    selection operating on structural diver-      may be distinguished: 1) rational design,
meters represent an adaptation of the         sity, directed by intra and intermolecular    which resides in looking for a single
system to environmental conditions, such      electromagnetic forces implementing           key, the correct one; 2) combinatorial
as medium (solvent), presence of inter-       molecular information and leading to the      chemistry, which relies on the generation
acting species (protons, metal ions,          progressive complexification of matter.       of vast collections of keys that may all
substrate molecules, etc.) or physical           CDC also encompasses dynamic coor-         be assayed by high throughput screening
factors (temperature, pressure, electric      dination chemistry,50,53,54 whereby the       with fast robotics. A third approach
or magnetic fields, etc.).                    coordination of metal ions induces the        results from the implementation of

This journal is ß The Royal Society of Chemistry 2007                                       Chem. Soc. Rev., 2007, 36, 151–160 | 155
Fig. 5 Constitutional dynamic selection driven by self-organisation in the formation of a G- quartet based gel: selection of the components that
generate the constituent B forming a strong gel.59 A, C and D do not form a gel.

CDC: 3) dynamic combinatorial/covalent           the goal that this virtual set of potential      with the target/lock, or kinetic selection,
chemistry (DCC), that relies on the              keys may contain one (or more) that              giving the key that forms fastest within
dynamic generation of interconverting            fits the lock, under either thermodynamic        the lock.52b In both cases, the supra-
keys resulting from all the possible             selection, expressing the constituent/key        molecular lock/key recognition interac-
combinations of fragments of keys, with          that presents the strongest interaction          tions direct the process (Fig. 9).




Fig. 6 Self-organisation with selection: dynamic selection of the components that generate the ligand forming a [2 6 2] grid-type complex driven
by metal ion coordination.62


156 | Chem. Soc. Rev., 2007, 36, 151–160                                           This journal is ß The Royal Society of Chemistry 2007
Fig. 7 Driven evolution of a constitutional dynamic library of helical strands under the pressure of metal ion coordination towards the generation
of the ligand strand (bottom right) that forms a [2 6 2] grid-type complex.63


   Whereas the usual ‘‘static’’ combina-          libraries,30 whose constituents comprise          The constituent(s) actually expressed/
torial chemistry is based on extensive            all possible combinations that may                selected among all those accessible is(are)
libraries of prefabricated molecules,             potentially be generated (but do not              expected, under thermodynamic control,
DCC implements the reversible con-                need to be present initially). It repre-          to be that(those) presenting the strongest
nection of sets of basic components               sents a powerful means for generating             interaction with the target, that is, the
to give access to virtual combinatorial           dynamic, effector-responsive diversity.           highest receptor/substrate molecular
                                                                                                    recognition. The overall process is thus
                                                                                                    instructed (target-driven), combinatorial,
                                                                                                    and dynamic. It bypasses the need to
                                                                                                    actually synthesize the constituents of
                                                                                                    a combinatorial library by letting the
                                                                                                    target perform the assembly of the
                                                                                                    optimal partner from a virtual set30,56
                                                                                                    of components.68
                                                                                                       3) One may define molecular and
                                                                                                    supramolecular dynamic materials, as
                                                                                                    materials whose components are linked
                                                                                                    through reversible covalent or non-
                                                                                                    covalent connections and undergo
                                                                                                    spontaneous and continuous change in
                                                                                                    constitution by assembly/deassembly
                                                                                                    processes in a given set of conditions.
                                                                                                    Via recognition-directed association and
                                                                                                    self-organisation processes, supramole-
                                                                                                    cular chemistry has opened new perspec-
                                                                                                    tives in materials science towards the
Fig. 8 Constitutional dynamic self-sensing: constitutional transformation of an aromatic–
                                                                                                    design and engineering of supramolecular
aliphatic dynamic polyimine (FlCy) into an aromatic–aromatic (FlFl) copolymer induced               materials. These, again, are dynamic by
by zinc(II) cations, with generation of a strong fluorescence signal in the presence of excess      nature, whereas molecular materials
zinc ions. The metal ions drive the formation of the entity that reveals their very presence in a   must be rendered dynamic by introduc-
self-sensing process.64                                                                             tion of reversible covalent connections

This journal is ß The Royal Society of Chemistry 2007                                               Chem. Soc. Rev., 2007, 36, 151–160 | 157
                                                                                                     for time-delayed, dynamic formulation
                                                                                                     and controlled release strategies for
                                                                                                     instance of antimicrobial agents72 or of
                                                                                                     fragrances.73 Fully inorganic materials
                                                                                                     of spherical shape have been generated
                                                                                                     from dynamic libraries.74
                                                                                                        CDC introduces into the chemistry of
                                                                                                     materials a basic shift with respect to
                                                                                                     constitutionally static materials and
                                                                                                     opens new perspectives in materials
                                                                                                     science. A rich variety of novel architec-
                                                                                                     tures, processes and properties may be
                                                                                                     expected to result from the blending of
                                                                                                     supramolecular and molecular dynamic
                                                                                                     chemistry with materials chemistry.

                                                                                                     Conclusion. Outlook:
Fig. 9 Schematic representation of the principle of dynamic combinatorial/covalentchemistry          Chemistry in five dimensions
(DCC) as applied in particular to the discovery of leads for bioactive compounds. A dynamic
library of constituent keys is generated from reversibly connecting fragments of the keys. The       Supramolecular chemistry has thus pro-
receptor/lock amplifies/favours the expression of the constituent/key that binds best to it          gressed over the years along three over-
(thermodynamic selection) or that forms fastest within it (kinetic selection). Bottom: the library   lapping phases. The first is that of
constituents/keys do not need to be formed before the addition of the receptor/lock, illustrating    molecular recognition and its corollaries,
the notion of virtual dynamic library.50,51                                                          supramolecular reactivity, catalysis, and
                                                                                                     transport; it relies on design and pre-
between building blocks. Because of their            Covalent dynamers may also present a            organisation and implements informa-
intrinsic ability to exchange their compo-        range of unusual properties such as cross-         tion storage and processing.
nents, they may in principle select them in       over component recombination between                  The second concerns self-assembly and
response to external stimuli or environ-          neat films in dynamic polymer blends               self-organisation, i.e., self-processes in
mental factors and therefore behave as            (Fig. 10)69 and soft-to-hard transforma-           general; it relies on design and imple-
adaptive materials of either molecular or         tion of polymer mechanical properties              ments programming and programmed
supramolecular nature.7,9,30                      through component incorporation.70                 systems, which involve messages in mole-
   Applying such considerations to poly-             Dynamic biomaterials may be of                  cules controlling the generation of spe-
mer chemistry leads to the definition             interest for biodegradability71 as well as         cific entities in complex mixtures.75
of constitutionally dynamic polymers,
dynamers, of both molecular and
supramolecular types,27–30 that have a
constitutional/combinatorial       diversity
determined by the number of different
monomers. The components effectively
incorporated into the polymers depend
on the nature of the connections (recog-
nition or functional groups) and core
groups, as well as on the interactions
with the environment, so that dynamers
possess the possibility of adaptation
by association/growth/dissociation sequ-
ences. The dynamic and combinatorial
features of dynamic polymers give access
to higher levels of behaviour such as
self-healing, adaptability, response to
external stimulants (heat, light, chemical
additives, etc.).
   In particular, a supramolecular polymer
chemistry has developed, concerning
polymers of supramolecular nature
generated by the self-assembly of mono-           Fig. 10 Dynamic polymer blends: schematic representation of crossover component recombi-
mers interconnected through complemen-            nation between neat films of dynamic covalent polyacylhydrazone copolymers. The coloured
tary interaction/recognition groups.27–30         units represent different monomers.69


158 | Chem. Soc. Rev., 2007, 36, 151–160                                             This journal is ß The Royal Society of Chemistry 2007
   The third concerns constitutional             Highly     interconnected     networks         14 G. W. Gokel and A. Mukhopadhyav,
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dynamics of both molecular and supra-         (reactionally, but also constitutionally)         15 D. T. Bong, T. D. Clark, J. R. Granja and
molecular entities, defining constitu-        relate to a systems chemistry.79 Further              M. R. Ghadiri, Angew. Chem., Int. Ed.,
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concept; it allows for adaptation and         hierarchical self-organisation on increas-        16 M. Irie, Chem. Rev., 2000, 100, 1683.
                                                                                                17 A. P. de Silva and N. D. McClenaghan,
evolution; it relies on self-organisation     ing scale,80 with emergence81 of novel                J. Am. Chem. Soc., 2000, 122, 3965.
with selection in addition to design,         features/properties at each level, self-          18 A. W. Czarnik and J. P. Desvergne,
and implements chemical diversity and         organisation in space as well as in                   Chemosensors for Ion and Molecule
‘‘informed’’ dynamics.75                      time,82 and passage beyond reversibility,             Recognition, Kluwer, Dordrecht, 1997.
                                                                                                19 J.-M. Lehn, Angew. Chem., Int. Ed. Engl.,
   CDC represents a paradigm shift with       towards self-organisation and con-                    1990, 29, 1304.
respect to constitutionally static chemis-    stitutional dynamics in non-equilibrium           20 J.-M. Lehn, Chem.–Eur. J., 2000, 6, 2097.
try. The latter relies on design for the      systems.                                          21 G. M. Whitesides, J. P. Mathias and
                                                                                                    C. T. Seto, Science, 1991, 254, 1312.
generation of a target entity, whereas           One may consider that CDC confers
                                                                                                22 D. S. Lawrence, T. Jiang and M. Levett,
CDC takes advantage of dynamic diver-         to chemistry a fifth dimension, that of               Chem. Rev., 1995, 95, 2229.
sity to allow variation and selection. The    constitution, in addition to the three            23 D. Philp and J. F. Stoddart, Angew.
implementation of selection in chemistry      dimensions of space (structure) and of                Chem., Int. Ed. Engl., 1996, 35, 1154.
                                                                                                24 (a) S. Leinninger, B. Olenyuk and
introduces a fundamental change in            time (kinetics). Thus, self-organisation
                                                                                                    P. J. Stang, Chem. Rev., 2000, 100, 853;
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the output molecular or supramolecular           In the context of the ‘‘big’’ problems         25 G. F. Swiegers and T. J. Malefetse, Chem.
                                                                                                    Rev., 2000, 100, 3483.
entity by explicit programming, self-         challenging science, where physics                26 L. F. Lindoy and I. M. Atkinson, Self-
organisation with selection operates          addresses the origin and laws of the                  Assembly in Supramolecular Systems,
on dynamic constitutional diversity76 in      universe, and biology those of life,                  Royal Society of Chemistry, Cambridge,
response to either internal or external       chemistry may claim to provide the                    2000.
                                                                                                27 (a) Supramolecular Polymers, ed. A. Ciferri,
factors to achieve adaptation in a            means for unravelling the progressive                 Dekker, New York, 2nd edn, 2005; (b)
Darwinistic fashion.                          evolution towards complex matter by                   J.-M. Lehn in Supramolecular Polymers,
   In the process of reaching higher levels   uncovering the processes that underlie                ed. A. Ciferri, Dekker, New York, 2nd edn,
                                                                                                    2005, ch. 1.
of self-organisation, CDC gives access to     self-organisation,7 and for implementing
                                                                                                28 J.-M. Lehn, Polym. Int., 2002, 51, 825.
the generation of networks of dynami-         the knowledge thus acquired to create             29 L. Brunsveld, B. J. B. Folmer, E. W. Meijer
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