European Review, Vol. 17, No.

2, 263–280 r 2009 Academia Europæa

doi:10.1017/S1062798709000805 Printed in the United Kingdom

Towards Complex Matter:

Supramolecular Chemistry and
Self-organization*

JEAN-MARIE LEHN
Institut de Science et d’Ingenierie Supramoléculaires, Université Louis
Pasteur, 67000 Strasbourg, France and Collège de France, 75005 Paris,
France. E-mail: [email protected]

Chemistry has developed from molecular chemistry, mastering the combination

and recombination of atoms into increasingly complex molecules, to supramo-
lecular chemistry, harnessing intermolecular forces for the generation of informed
supramolecular systems and processes through the implementation of molecular
information carried by electromagnetic interactions. Supramolecular chemistry is
actively exploring systems undergoing self-organization, i.e. systems capable of
spontaneously generating well-defined functional supramolecular architectures by
self-assembly from their components, on the basis of the molecular information
stored in the covalent framework of the components and read out at the supra-
molecular level through specific molecular recognition interactional algorithms,
thus behaving as programmed chemical systems. Supramolecular entities as well
as molecules containing reversible bonds are able to undergo a continuous change
in constitution by reorganization and exchange of building blocks. This capability
defines a Constitutional Dynamic Chemistry (CDC) on both the molecular and
supramolecular levels. CDC introduces a paradigm shift with respect to con-
stitutionally static chemistry. It takes advantage of dynamic constitutional
diversity to allow variation and selection and thus adaptation. The merging of the
features of supramolecular systems – information and programmability; dynamics
and reversibility; constitution and structural diversity – points towards the
emergence of adaptive chemistry. A further development will concern the
inclusion of the arrow of time, i.e. of non-equilibrium, irreversible processes and
the exploration of the frontiers of chemical evolution towards the establishment of

*From Proceedings of the National Academy of Sciences of the United States of America (2002), 99, 4763–4768. This
is an edited version of the article ‘Towards complex matter: Supramolecular chemistry and self-organization’ by Jean-
Marie Lehn.
264 Jean-Marie Lehn

evolutive chemistry, where the features acquired by adaptation are conserved and
transmitted. In combination with the corresponding fields of physics and biology,
chemistry thus plays a major role in the progressive elaboration of a science of
informed, organized, evolutive matter, a science of complex matter.

As the wind of time blows into the sails of space, the unfolding of the universe
nurtures the evolution of matter under the pressure of information. From divided
to condensed and on to organized, living, and thinking matter, the path is toward
an increase in complexity through self-organization.
Thus emerges the prime question set to science, in particular to chemistry, the
science of the structure and transformation of matter: how does matter become
complex? What are the steps and the processes that lead from the elementary
particle to the thinking organism, the (present) entity of highest complexity?
And there are two linked questions: an ontogenetic one, how has this happened,
how has matter become complex in the history of the universe leading up to the
evolution of the biological world; and an epigenetic one, what other and what
higher forms of complex matter can there be to evolve, are there to be created?
Chemistry provides means to interrogate the past, explore the present, and build
bridges to the future. Molecular chemistry has created a wide range of ever more
sophisticated molecules and materials and has developed a very powerful arsenal of
procedures for constructing them from atoms linked by covalent bonds.
Beyond the molecule, supramolecular chemistry aims at developing highly
complex chemical systems from components interacting by non-covalent inter-
molecular forces.1,2 This has, over the last quarter of a century, grown into a major
field and has fuelled numerous developments at the interfaces with biology and
physics, thus giving rise to the emergence and establishment of supramolecular
science and technology as a broad multidisciplinary and interdisciplinary domain
providing a highly fertile ground for the creativity of scientists from all origins.
Rather than adding another facet to this already breathtaking panorama, it
appeared appropriate here to emphasize perspectives and provide a vision. This
essay therefore will not be extensively documented (numerous reviews and
books are available) but rather it will outline some conjectures for the future,
mainly based on, illustrated by, and extrapolated from work performed in the
author’s laboratories. Looking toward the horizon of supramolecular chemistry,
and more generally of supramolecular science,1,3 special attention will be given
to exposing the forest(s) rather than to describing the trees.

Supramolecular chemistry and the information paradigm

One of the major lines of development of chemical science resides in the ever
clearer perception, deeper analysis, and more deliberate application of the
 Towards Complex Matter 265

information paradigm in the elaboration and transformation of matter, thus tra-

cing the path from merely condensed matter to more and more highly organized
matter toward systems of increasing complexity. In chemistry, as in other areas,
the language of information is extending that of constitution, structure, and
transformation as the field develops toward increasingly complex architectures
and behaviours. It will profoundly influence our perception of chemistry, how we
think about it, how we perform it.
Supramolecular chemistry has paved the way toward apprehending chemistry
as an information science through the implementation of the concept of mole-
cular information with the aim of gaining progressive control over the spatial
(structural) and temporal (dynamic) features of matter and over its complex-
ification through self-organization, the drive to life.4–6
Supramolecular chemistry has developed as the chemistry of the entities
generated by intermolecular non-covalent interactions.1,2 Through the appro-
priate manipulation of these interactions, it became progressively the chemistry
of molecular information, involving the storage of information at the molecular
level, in the structural features, and its retrieval, transfer, and processing at the
supramolecular level, by interactional algorithms operating through molecular
recognition events based on well-defined interaction patterns (hydrogen bonding
arrays, sequences of donor and acceptor groups, ion coordination sites, etc). This
venture involved the design and investigation of more or less strictly preorganized
molecular receptors of numerous types, capable of binding specific substrates with
high efficiency and selectivity.
Three overlapping phases may be considered in the development of supra-
molecular chemistry, each exploring a main theme.
The first theme is that of molecular recognition and its corollaries, supra-
molecular reactivity, catalysis, and transport; it relies on design and preorganization
and implements information storage and processing.
The second concerns self-assembly and self-organization, i.e. self-processes in
general; it relies on design and implements programming and programmed
systems.
The third, emerging phase, introduces adaptation and evolution; it relies on
self-organization through selection in addition to design, and implements che-
mical diversity and ‘informed’ dynamics.

From preorganization toward self-organization and programmed

systems: design
Supramolecular chemistry has first relied on preorganization for the design of
molecular receptors effecting molecular recognition, catalysis, and transport
processes.1,2
266 Jean-Marie Lehn

Supramolecular preorganization has also provided new ways and means for
chemical synthesis.1,7–9 Supramolecular, non-covalent synthesis, i.e. the con-
struction of the supramolecular entities themselves, rests on the making and
breaking of non-covalent bonds following an Aufbau strategy incorporated into
the design of the molecular components. On the other hand, supramolecular
assistance to synthesis provides a powerful tool involving first the non-covalent
synthesis of a supramolecular architecture, which positions the components,
followed by post-assembly modification through covalent bond formation. Both
areas will continue to provide in the future a range of highly sophisticated non-
covalent as well as covalent entities. A particularly impressive illustration of the
latter is the synthesis of interlocked compounds (see below).
Beyond preorganization lies the design of systems undergoing self-organiza-
tion, i.e. systems capable of spontaneously generating well-defined, organized,
and functional supramolecular architectures by self-assembly from their com-
ponents, thus behaving as programmed systems.1,10 Chemical programming
requires the incorporation into molecular components of suitable instructions for
generation of a well-defined supramolecular entity. The program is molecular, the
information being contained in the covalent structural framework; its operation is
supramolecular, making use of recognition algorithms based on specific inter-
action patterns. Understanding, inducing, and directing self-processes is key to
unravelling the progressive emergence of complex matter. Self-organization is
the driving force that led up to the evolution of the biological world from
inanimate matter.4–6
Whereas self-assembly may be taken as simple collection and aggregation of
components into a confined entity, we shall here consider self-organization as the
spontaneous but information-directed generation of organized functional struc-
tures in equilibrium conditions. A relevant biological example is, for instance, the
formation of a virus particle from its components, genomic nucleic acid and coat
proteins. The inclusion of dissipative, non-equilibrium processes, as present in
the living world, constitutes a major goal and challenge for the future.4–6
A self-organization process may be considered to involve three main stages:
(i) molecular recognition for the selective binding of the basic components;
(ii) growth through sequential and eventually hierarchical binding of multiple
components in the correct relative disposition; it may present cooperative and
nonlinear behaviour; and (iii) termination of the process, requiring a built-in
feature, a stop signal, that specifies the end point and signifies that the process
has reached completion.
Suitable encoding by manipulation of structural subunits and processing
through interactional algorithms should give access to a variety of systems. More
or less strict programming of the output species may be achieved depending on
the robustness of a given directing code (for instance, of hydrogen bonding or
 Towards Complex Matter 267

metal coordination nature), i.e. on the extent to which it is sensitive to perturbations.

In a robust system, the instructions are strong enough to ensure the stability of the
process, i.e. the self-organization is resistant, stable toward interfering interactions
(such as secondary metal coordination, van der Waals stacking, etc) or toward
modifications of parameters (such as concentrations and stoichiometries of the
components, presence of foreign species, etc). When the assembly occurs only in a
narrow range of conditions, the system is unstable and presents a singularity; it may
also display a bifurcation or a switching point between different assemblies. On the
other hand, sensitivity to perturbations, while limiting the operation range, introduces
diversity and adaptability (3) in the self-organization process.
Self-selection with self-recognition occurs when the structural instructions are
sufficiently strong, as is the case in the ‘correct’ pairing of strands of different lengths
in the assembly of helicates, inorganic double helices.11 The process bears relation to
the implementation of combinatorial chemistry in its ‘dynamic’ version (see below).
It reveals a broader perspective with a paradigm shift, from ‘pure compounds’ to
‘instructed mixtures’, from ‘unicity’ to ‘multiplicity 1 information’.11 Rather than
pursuing mere chemical purity of a compound or a material, one seeks to design
instructed components, which, as mixtures, allow the controlled assembly of mul-
tiple well-defined supramolecular species, following specific programs and interac-
tional algorithms. The implementation of this instructed mixture paradigm is crucial
for the development of complex chemical systems, as witnessed by the build-up of
organized species and the execution of highly integrated functions that take place
side-by-side in the assembly and in the operation of the machinery of the living cell.
Intense activity has been devoted to the explicit application of molecular
recognition to control the formation, from their components, of organized supra-
molecular entities presenting specific physical and chemical properties. Three main
types of investigations have been pursued, based on the use of hydrogen bonding,
donor acceptor, and metal coordination interactions for controlling the processes
and holding the entities together.12–18 The latter have been instrumental in the initial
introduction of the notions of self-assembly into supramolecular chemistry.1,10 The
clever exploitation of templating and self-organization has given access to a range
of molecular and supramolecular entities of truly impressive structural complexity,
which otherwise would have been considered impossible to construct, such as
interlocked entities, whose components are mechanically held together15,19 and
multicomponent organic or inorganic architectures.1,12–18
Because it is a time-dependent process, self-organization also involves tem-
poral information and may display kinetic control, generating kinetic products
before reaching the thermodynamic one(s). This is the case in the initial assembly
of a triple helical complex that evolves toward a circular helicate.20 Such a
process may either be sequential, if the kinetic product is an intermediate located
on the pathway toward the final product, or it may be bifurcated, if this is not so.
268 Jean-Marie Lehn

A sequential process may be either commutative, if given steps may be

interchanged along the overall pathway leading to the final superstructure, or it
may be non-commutative if its progressive build-up occurs through a defined
sequence of molecular instructions and algorithms, where the generation of a
given intermediate depends on the previous one and sets the stage for the next
one. For example, discotic liquid crystals formed by the assembly of ‘sector’-
shaped components into disks, which thereafter organize into columns,21 and
template binding by molecular strands induces wrapping into helical disk-like
objects, which then aggregate into large supramolecular assemblies.22
The generation of supramolecular architectures and materials through a non-
commutative sequence of steps amounts to multilevel hierarchical self-organiza-
tion, along primary, secondary, tertiary, etc, structures. Such conditional processes
enable the progressive build-up of increasingly complex systems in a directed,
temporally ordered fashion; they also offer the intriguing possibility to intervene at
each step so as either to suppress the following ones or to reorient the subsequent
evolution of the system into another direction, toward another output entity.

Multiple self-organization through multiple processing/expression

of molecular information
The generation of a given superstructure through self-organization results, in its
simplest form, from the operation of a single-code assembly program. A step
beyond consists of devising systems of higher complexity that operate in mul-
timode fashion through the implementation of several codes within the same
overall program, resulting in multiple self-organization processes.3,23
Such behaviour may take place in the generation of different metallo-architectures
from the same ligand when using different sets of metal ions/coordination algorithms
for reading the binding information, as in the generation of two different helicates
from the same strand3,24 and in the assembly of ligands containing two different
subunits coding, respectively, for the formation of a helicate and a (2 3 2) grid-type
complex.25 Similarly, the differential expression of hydrogen bonding information
contained in a molecular strand may yield different supramolecular structures
depending on the processing mode (angular or linear) defined by the recognition
algorithm of the bound effector.22 These considerations lead to conjectures that
may have far-reaching implications and open novel perspectives within the
general framework of self-organizing, programmed chemical systems.23
The processing of the same ligand information by different interaction algo-
rithms (e.g. through the use of different sets of metal ions or of different
H-bonding effectors) allows the controlled self-organization of different output
architectures, resulting in multiple expressions of molecular information, through
post-informational (post-genomic) operations. Such a one-code/several-outputs
 Towards Complex Matter 269

scheme, in addition to the one-code/one-output (product) mode, also has, in

principle, significant implications in biology.
Multi-subroutine self-assembly may display three types of behaviour: (i) it may
behave as a linear combination of the subprograms, each running independently to
generate its own encoded output; self-recognition11 is a related process; (ii) it may
present crossover, when the subprograms operate in a combined fashion; or (iii) it
may also be of dominant/recessive type, one of the subprograms imposing its own
output over the other one(s).26
Multiple processing capacity represents a further step in the design of pro-
grammed chemical systems of increasing complexity capable of producing a
variety of more and more complex architectures as outputs.
Parallel processing, extending eventually to massively parallel systems, would
involve the simultaneous operation of multiple self-organization processes
toward the generation of a single functional entity or several different ones. The
side-by-side formation of different helicates11 or helicates and inorganic grids72
in a mixture of the corresponding ligands and suitable metal ions may be seen as
prototypes on a simple level.
Multiple processing of a single set of instructions allows the generation of
diversity, because multiple outputs may either coexist, or be potentially acces-
sible (virtual diversity).27 It thus meets dynamic combinatorial chemistry (DCC)
(see below).
Conversely, such chemical systems also open perspectives for information
science, inasmuch as they raise the question of going beyond the usual one-
to-one correspondence, established by a given program, between the input
information and a single output, toward multiple outputs generated by different
modes of processing the same information.
The combination of different recognition/instruction features in a molecular
program opens a door to the design of self-organizing systems capable of per-
forming molecular computation. Computing by self-assembly may yield a
powerful alternative to conventional models.28,29 Recent studies described the
use of biomolecules and DNA-based protocols to solve computational pro-
blems.30–32 An approach making use of specifically designed non-natural com-
ponents could provide higher diversity, better resistance to fatigue, and more
compact/smaller size. Such potential is latent in the coordination-controlled
assembly of double helicates3,24 and metallosupramolecular architectures,25 as
well as in the differential folding processes induced by effector H-bonding.22
Numerous types of interactions and recognition units, be they of inorganic or
organic nature, are available for exploring these avenues.
The combination of multiple expressions with reversible diversity genera-
tion suggests the notion of dynamic computing through dynamic information
generation and processing, defining adaptive/evolutive programmed systems.
270 Jean-Marie Lehn

Evolutionary computation may be envisaged with biomolecules,28,32,33 but

entirely synthetic molecular systems or mixed abio/bio ones should in the future
be amenable to similar feats, with probable advantages in design, control, and
diversity.

Dynamic chemistry and constitutional diversity: selection

Supramolecular chemistry is, by nature, a dynamic chemistry in view of the lability

of the interactions connecting the molecular components of a supramolecular entity.
The reversibility of the associations allows a continuous change in constitution,
which may be either internal, by rearrangement of the components with modification
of the connectivity between them, or external, by exchange, incorporation, or
extrusion of components, therefore conferring constitutional plasticity to the system.
Thus, supramolecular chemistry is a constitutional dynamic chemistry (CDC).
Dynamic chemistry also can be just morphological, involving reversible
changes in shape through molecular or supramolecular conformational or con-
figurational modifications, without change in (internal or external) constitution
and resulting in motional processes.
CDC may be molecular as well as supramolecular when the components of the
molecular entity are linked by covalent bonds that may form and break rever-
sibly. This ability to undergo continuous and reversible change by reorganization,
deconstruction, and reconstruction (alike or different) generates constitutional
dynamic diversity. It allows us to perform selection of a given constituent, made
up of a well-defined set of components in the pool of compounds having all
possible constitutions, under the pressure of either internal (intrinsic stability of
the species, as in helicate self-recognition11) or external (interaction with species
in the environment, as in anion binding by circular helicates34,35) factors.
CDC thus constitutes a general area of which one specific expression, when
under combinatorial conditions, is DCC that has actively developed in recent
years.27,36,37 It relies on the dynamic generation of molecular and supramolecular
diversity through the reversible combination of covalently or non-covalently
linked building blocks (components). Whereas combinatorial chemistry itself is
based on extensive libraries of prefabricated molecules, DCC implements the
reversible connection of pools of basic components to give access to virtual
combinatorial libraries (VCLs) whose constituents comprise the full set of all
possible combinations that may potentially be generated in dynamic equilibrium.
The constituents actually expressed among all those accessibles are expected to
be those presenting the strongest interaction with a given target, i.e. the fittest.
DCC bypasses the need to actually synthesize the library constituents and lets the
target select the optimal partner by inducing its preferential assembly from its
 Towards Complex Matter 271

components, eventually with a facilitation of the connecting reaction. It is thus a

target/function-driven self-organization, i.e. a self-design process (see below).
The basic features of the DCC/VCL approach have been presented together with
its implementation in different fields and the perspectives it offers in a variety of
areas of science and technology, such as the discovery of biologically active
substances, new materials, and catalysts, etc.27
CDC introduces a profound change in paradigm and opens a range of novel
perspectives with respect to constitutionally static chemistry (see also Refs 38 and
39). Whereas the latter relies on design for the generation of a target molecule or
supermolecule, CDC takes advantage of dynamic diversity to allow variation and
implements selection to achieve adaptation in a Darwinistic fashion.

Self-organization by design and selection: self-design

Whereas preorganization relies entirely on design, supramolecular self-organization
introduces in addition the possibility to let the system build up by selection.
Self-organization by design has been pursued with the goal to achieve full
control over the output supramolecular entity by means of correctly instructed
components, specific interaction algorithms, and (as much as possible) strict pro-
gramming. Design is knowledge-based and has an explicit information content.
Self-organization by selection requires dynamic diversity (constitutional and/or
morphological) on which to operate. This is made possible by the implementation
of CDC responding to the pressure of either internal or external factors. Selection
has an implicit information content. It is also truly a supramolecular process,
because it occurs in relation to interactions with surroundings (which may be either
the medium or a more or less distant part of a folded macromolecule).
The introduction of the selection paradigm into (supramolecular) chemistry
brings about a fundamental change in ways, means, and outlook. Of course, the
question is not to replace the deliberately planned linear process of design by a
multipronged trial-and-error process of selection. Design and selection are not
mutually exclusive but are complementary for reaching systems of higher
complexity through self-organization. The ultimate goal is to merge design and
selection in self-organization to perform self-design, where function-driven
selection among suitably instructed dynamic species generates the optimal
organized and functional entity. In fact, self-recognition in helicate self-assembly
from mixtures of ligand strands,11 the selection of monomers in the synthesis of
molecular helices under the pressure of folding40 as well as the formation of
dynamic helical polymers73 may be perceived as such internally driven systems.
Altogether, harnessing the power of selection for adaptation and evolution on
the molecular scene is ushering in a Darwinistic era into chemistry, where the
fittest species survive.
272 Jean-Marie Lehn

Self-organization of functional supramolecular systems

The self-organization of functional supramolecular entities concerns either dis-

crete species or, on the other hand, extended assemblies in one (e.g. poly-
molecular chains, fibres), two (e.g. layers, membranes), and three (e.g. solids)
dimensions.
Functional supramolecular devices are based on the structural organization and
functional integration of active components operating with photons, electrons,
and ions or presenting chemical reactivity.
Photoactive and electroactive devices performing energy or electron exchange/
transfer processes form the core of molecular and supramolecular photonics and
electronics.41–45 They have, for instance, led to labelling and detection proce-
dures of interest for biological studies and medical diagnostics based on energy
transfer. Redox processes have been used for developing prototypes of molecular
electronic components, such as molecular wires, batteries, and rectifiers. The
combined operation of photo- and electro-effects gives rise to photoinduced
electron transfer and charge separation, so that a major thrust has been toward the
mimicking of the first steps of photosynthesis.45 The search for artificial ion
carriers and ion channels provides the basis for (supra)molecular ionics.41,42,46,47
Controlling the transfer of photons, electrons, and ions sets the stage for semi-
ochemistry,10 the chemistry of signal generation and processing, of interest for
instance in devising sensing and logic functions.48,49 Developments toward
supramolecular technology have been actively pursued, concerning in particular
sensors and other optical or electronic devices, possibly of interest for ‘molecular
computing’.42,50
Mechano-devices, effecting triggered molecular motions, belong to a general
area of dynamic devices. Molecular motions and changes in molecular shape
may be produced through external stimuli in various systems, e.g. cis-trans
isomerization in azobenzene derivatives and optical changes in photochromes
are accompanied by large geometric variations. Interlocked and intertwined
structures have been used for the photochemical or electrochemical induction of
relative motion between the mechanically linked components. They have given
access to a range of intriguing processes (e.g. shift registers, circular displace-
ments) related in particular to the design of ‘molecular machines’ and the
induction of directional motion.51–53
While the above devices present physical functionality, chemically reactive
self-organized entities are formed when the assembling brings together compo-
nents bearing reactive functional groups. Through the appropriate disposition of
specific subunits in an organized pattern, they may be amenable to perform
efficient and selective reactions and catalysis. Such supramolecular processes
involve first a substrate recognition step followed by a chemical transformation
 Towards Complex Matter 273

on the bound entity,1 resulting in an activity of artificial enzyme type. When the
reactions occur within the self-assembled entity, they amount to self-transfor-
mation and may in particular result in replication and self-replication pro-
cesses.39,54,55 They may present autocatalysis, a behaviour that together with the
establishment of networks of reactions and coupled catalytic cycles amounts to
self-organization on the chemical reactivity level, presenting features such as
self-regulation, feedback, and amplification. The controlled self-organization of
functional systems displaying reactivity and catalysis is crucial for the develop-
ment of chemical systems of both structural and reactional complexity. It has
played a key role in biological evolution4 and presents a major challenge to
chemistry.

Functional supramolecular materials

The properties of a material depend both on the nature of its constituents and the
interactions between them. Supramolecular chemistry may thus be expected to
have a strong impact on materials science by means of the explicit manipulation
of the non-covalent forces that hold the constituents together. These interactions
and the recognition processes that they underlie allow the design of materials and
the control of their build-up from suitable units by self-organization. Thus,
supramolecular chemistry opens new perspectives in materials science toward an
area of supramolecular materials, ‘smart’ materials whose features depend on
molecular information. For instance, liquid-crystalline polymers of supramolecular
nature have been obtained by the self-assembly of complementary subunits.56–58
Supramolecular materials are by nature dynamic materials, materials whose
constituents are linked through reversible connections and which may undergo
assembly/deassembly processes in specific conditions. Because of this intrinsic
ability to exchange their constituents, they are constitutionally dynamic materials
and may in principle select their constituents in response to external stimuli or
environmental factors. Supramolecular materials thus are instructed, dynamic,
and combinatorial and behave as adaptive materials.3
A rich domain emerges from the combination of polymer chemistry with
supramolecular chemistry defining a supramolecular polymer chemistry.56–58 It
involves the designed manipulation of molecular interactions (hydrogen bonding,
donor-acceptor effects, etc) and recognition processes to generate main-chain (or
side-chain) supramolecular polymers by the self-assembly of complementary
monomeric components (or by binding to lateral groups). In view of their lability,
these associations present features of reversible, ‘living’ polymers capable of
growing or shortening, of rearranging or exchanging components. Supramole-
cular polymers are thus constitutionally dynamic materials, based on dynamic
polymer libraries whose members possess constitutional diversity determined by
274 Jean-Marie Lehn

the nature and variety of the different monomers. The components effectively
incorporated into the polyassociations depend in particular on the nature of the
recognition and core groups, internal structural compatibility, as well as the
interactions with the environment. These features give access to higher levels of
behaviour such as healing, adaptability, response to external stimulants (heat,
light, additives, etc) by association/growth/dissociation sequences.
The selective, recognition-controlled incorporation of components presenting
specific functional properties (energy transfer, electron transfer, ion binding, etc)
allows us to envisage applications for such diverse purposes as drug delivery,
gene transfer, mechanical action (e.g. triggered changes in shape or size), visc-
osity adjustment, hydrophilicity/hydrophobicity modulation, optical and elec-
tronic effects, etc.
Supramolecular versions of the various species and procedures of molecular
polymer chemistry may be imagined and implemented, providing a wide field of
future investigation that may offer a wealth of novel entities and functionalities.
Similar considerations apply to the generation of supramolecular liquid crystals.56–58
Molecular recognition may be used to induce and control self-organization in
two and three dimensions for performing supramolecular engineering of poly-
molecular assemblies and materials, layers, films, membranes, micelles, gels,
mesophases, and solids as well as on surfaces or at interfaces.
Surfaces modified with recognition units may display selective surface binding
on the microscopic level and recognition-controlled adhesion on the macroscopic
scale. Intermolecular interactions may be brought to induce the controlled
assembly of macroscopic objects as is the case with capillary forces.59
Self-organization of polymolecular assemblies reaches a second level in the self-
organization of objects that are themselves self-organized. Vesicles are of special
interest in this respect, because compartmentalization must have played a major role
in the self-organization of complex matter and thus in the evolution of living
cells and organisms. One may envisage the controlled build-up of architecturally
organized and functionally integrated polyvesicular systems toward the design of
artificial cells and polymolecular systems of tissue-like character, implementing
specific intravesicular and intervesicular processes.60,61 The manipulation of the
features of vesicles and their behaviour is a step in this direction; thus, liposomes
decorated with recognition groups, recosomes, present features such as selective
interaction with molecular films, aggregation, and fusion.62,63
Molecular recognition interactions also provide a powerful entry into solid-
state chemistry and crystal engineering. The increasing ability to control the way
in which molecules associate gives means for the designed generation of
supramolecular architectures in the solid state.64
The generation of self-organized nano-structures, organized and functional
species of nanometric dimensions, defines a supramolecular nanochemistry.
 Towards Complex Matter 275

Supramolecular nanochemistry and nanomaterials

Nanoscience and nanotechnology are receiving great attention in view of both
their basic interest and their potential applications.65,66 Here again, supramole-
cular chemistry and self-organization contribute a fundamentally novel outlook
of deep impact. Three approaches to these areas may be considered.

(i) The miniaturization, top-down ‘size-shrinking’ approach, mainly

pursued up to now, has led to the tremendous achievements of the
microelectronics technology and is pushing down the limits of size
and compactness of components and devices.
(ii) The nanofabrication and nano-manipulation bottom-up approach to
molecular nanotechnology, takes advantage of novel nanolevel
materials and methods (e.g. near-field scanning microscopies) to
generate nanoentities presenting intriguing potential, such as electrical
devices built on carbon nanotubes (for two recent examples, see Refs
67 and 68) or optical devices such as optical sieves.69
(iii) The supramolecular self-organization approach, where the goal is
not smaller size or individual addressing but complexity through
self-processing, strives for self-fabrication by the controlled
assembly of ordered, fully integrated, and connected operational
systems by hierarchical growth.

The first two approaches rely on design and implement physical procedures.
Self-organization may take advantage of both design and selection, through its
informed, dynamic and adaptive features, and finds inspiration in the integrated
processes of biological systems.
Indeed, the spontaneous but controlled generation of well-defined, functional
supramolecular nanostructures through self-organization offers a very powerful
alternative to nanofabrication and nano-manipulation, bypassing the implementation
of tedious procedures and providing a chemical approach to nanoscience and tech-
nology. Rather than having to top-down prefabricate or to stepwise construct
nanostructures, more and more powerful methodologies resorting to self-organization
from instructed components will give access to highly complex functional archi-
tectures.1 Their dynamic features, allowing constitutional modification through
exchange of components, confer on them the potential to undergo healing and
adaptation, processes of great value for the development of ‘smart’ nanomaterials.
Of course, various combinations of self-organization and fabrication procedures
may be envisaged and implemented at different stages.
Fabricating, manipulating, and implementing nano-size chemical entities offer
a wide range of potential applications of great value for science and technology.70
Reducing size to the nano-object and addressing it are admirable feats that
276 Jean-Marie Lehn

provide entirely new insight into the properties and functioning of chemical as
well as biological systems. However, in the long run, the goal is complex
organization and collective operation rather than smaller size and individual
addressing. And here the path is traced by self-organization, covering a full range
of self-processes that determine the internal build-up and the operation of the
entity (self-selection, self-wiring), as well as its interaction with the environment
(self-connection for addressing and sensing). It follows also a bottom-up scale
change by growth from the nanolevel to the meso level and to the macrolevel
with internal structural organization, functional integration, and external con-
nection. Indeed, the most complex object around, the brain, builds up by self-
organization and is self-wired and self-integrated as well as self-connected
through our senses.

Toward adaptive and evolutive chemistry

The combination of the features of supramolecular systems – information and pro-
grammability, dynamics and reversibility, constitution and diversity – leads toward
the emergence of adaptive/evolutive chemistry.3 It is, by essence, of supramolecular
nature because it is determined by interaction with an external entity. It may be
constitutional and/or morphological (as occurs in ‘induced fit’ for instance).
Adaptive chemistry implies selection and growth under time reversibility.
Implementing both design and selection, self-organization offers adjustability
(through self-correction, self-healing under internal dynamics); adjustability
leads to adaptation (through reorganization under interaction with environmental
effectors); adaptation becomes evolution, when acquired features are conserved
and passed on.
Adaptation is illustrated by functionally driven optimization through selection
from pools of dynamically interconverting supramolecular species. Evolutive
chemical systems suppose multiple dynamic processes with sequential selection/
acquisition/fixation steps and undergo progressive change of internal structure
under the pressure of environmental factors. But the world of selection is a brutal
world, where only the fittest survives. It is ultimately for thought and design to
open up a post-Darwinian era by recruiting the forces of information to override
the dictate of selection.
Beyond programmed systems and in line with an evolutive chemistry, the next
step in complexity consists of the design of chemical ‘learning’ systems, systems
that are not just instructed but can be trained (see for instance Ref. 71).
The incorporation of the arrow of time, time irreversibility, leads to self-organi-
zation in non-equilibrium, dissipative systems through irreversible processes.4,5 It
implies the passage from closed systems to open and coupled systems that are
connected spatially and temporally to their surroundings.
 Towards Complex Matter 277

Supramolecular science, the science of informed, complex matter

In the long-range perspective, the development of chemical science is towards
complex systems, spanning the broadest outlook from divided to condensed
matter then to organized and adaptive matter, on to living matter and think-
ing matter, up the ladder of complexity. Complexity implies and results from
multiplicity of components, interaction between them and integration, i.e. cor-
relation, coupling, and feedback.1 The species and properties defining a given
level of complexity result from, and may be explained on the basis of, the species
belonging to the level below and of their multibody interaction, e.g. supramo-
lecular entities in terms of molecules, cells in terms of supramolecular entities,
tissues in terms of cells, organisms in terms of tissues and so on, up to the
behaviour of societies and ecosystems along a hierarchy of levels defining the
architecture of complexity. At each level of increasing complexity, novel features
emerge that do not exist at lower levels, which are deducible from but not
reducible to those of lower levels.
Supramolecular chemistry provides ways and means for progressively unravel-
ling the complexification of matter through self-organization.
Together with the corresponding areas in physics and biology, supramolecular
chemistry builds up a supramolecular science whose already remarkable
achievements point to the even greater challenges that lie ahead. They lead to a
science of complex matter, of informed, self-organized, evolutive matter. The
goal is to progressively discover, understand, and implement the rules that
govern its evolution from inanimate to animate and beyond, to ultimately acquire
the ability to create new forms of complex matter. The perspectives opened up
become wider and wider as progress is being made and will constitute horizons
of the future for quite some time.

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About the Author

Jean-Marie Lehn was born in Rosheim, France in 1939. In 1970 he became
Professor of Chemistry at the Université Louis Pasteur in Strasbourg and since
1979 he has been Professor at the Collège de France in Paris. He shared the
Nobel Prize in Chemistry in 1987 for his studies on the chemical basis of
‘molecular recognition’ (i.e. the way in which a receptor molecule recognizes
and selectively binds a substrate), which also plays a fundamental role in bio-
logical processes. Over the years his work led to the definition of a new field of
chemistry, which he has proposed calling ‘supramolecular chemistry’ as it deals
with the complex entities formed by the association of two or more chemical
species held together by non-covalent intermolecular forces, whereas molecular
chemistry concerns the entities constructed from atoms linked by covalent bonds.
Subsequently, the area developed into the chemistry of ‘self-organization’ pro-
cesses and more recently into ‘constitutional dynamic chemistry’. Author of
more than 800 scientific publications, Lehn is a member of many academies and
institutions. He has received numerous international honours and awards.
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