Emerging Complexity in Supramolecular Systems

Strasbourg Complex Systems Roadmap

Participants

• Nicolas Giuseppone
• Emilie Moulin
• Mihail Stadler,
• Antoine Bonnefont,
• Franck Hoonakker
• Mario Ruben
• Jean-Marc Planeix,
• Mourad Elhabiri,
• Stéphane Mery

Keywords

Hierarchical structures, Dynamic systems, Adaptive behaviour, Molecular evolution, Smart functional systems, Information-gaining systems

Introduction

One might consider complex supramolecular systems as large collections of molecules structured through hierarchical levels of reversible interactions. The complexity of these systems results from the combination of three key parameters which necessitate well-defined chemical characteristics:

• Multiplicity

Each individual molecular species in these systems already contain intrinsic multiplicity regarding the number of their binding sites, of their energy levels, of their conformational minima, etc. In addition, the combinatorial nature of complex systems in terms of number of interacting constituents leads to multiplicity of the potentially formed species.

• Interaction

Interactions between constituents and components in these systems are ruled by the complementarity of their shapes, of their charges, and of their energy levels. This combination represents an algorithm encoded at the molecular level which can be read at the supramolecular one to produce more advanced architectures. The dynamic of these interactions is extremely important and is governed by the reversibility and the lability of covalent or non-covalent bonds. Interactions also occur between these systems and their environments, especially because supramolecular interactions are relatively weak and can sense modest variations of the surrounding energy. This allows the systems to switch altenatively between different thermodynamic minima, or to be pushed far from equilibrium when crossed by flux of energy.

• Integration

Integration results from the collective structuring of molecular species in space (from subnano-, to meso-, and possibly to macroscopic scales), but also in time (with the modulation between structures along precise kinetic parameters). In addition, when several reactions are linked through coupled equilibria in networks, feedback loops and spatial coupling processes can take place, integrating properties which allow the emergence of new multiscale functions related to the topology of these networks and to their kinetic parameters.

To design and manipulate such systems up to the production of emerging functions, a number of challenges should be identified and addressed.

Grand Challenges

1. Designing supramolecular systems able to generate complexity
2. Reaching emergent properties in complex supramolecular systems
3. Using complex supramolecular systems for applications with high societal implications
4. Creating plateforms

1. Designing supramolecular systems able to generate complexity

The conception of complex supramolecular systems requires first to understand and engineer specific tools before bringing them all together.

Specificity of interactions and integrations

Synthetic chemistry - often supported by modelling - remains the prerequisite to design any molecular and supramolecular systems. Because the specificity of supramolecular objects leads to hierarchical structures, the information contained in the basic building blocks should be precisely tailored. This stands for small host-guest complexes with a high degree of organization, but also for objects with longer range organizations.

Spatio-temporal dynamics at the Multiplicity, Interaction, and Integration levels

Thermodynamics governs (supra)molecular systems at a number of levels. For instance, conformational dynamic rests on the transient conformations of individual molecules and can affect their interactions with the other constituents of the system. In addition, constitutional dynamic refers to objects reversibly connected to one another in larger aggregates under thermodynamic control, although these systems can be pushed far from equilibrium when crossed by various flux of energies including photochemical and electrochemical triggers, electric and magnetic fields, shearing forces, and gradients of chemical species. Dynamic is finally a key parameter characterizing networks of chemical reactions because the relative ratii of concentrations and kinetic rates, depending on the network topologies, provide new properties such as stability, robustness, spatial and temporal organization forming patterns, oscillations, and waves. Together, the dynamics occuring at the molecular, supramolecular, and network levels are intricated to allow adaptation processes.

Chemical reversibility as a requirement for evolvability

The reversibility of chemical reactions and supramolecular interactions is mandatory for two main aspects. The first one concerns the necessity to explore the whole combinatorial space of the potential structures. These species should not be necessary expressed by the system at all time, but they should be able to emerge when necessary (virtuality). The second aspect, which is a consequence of the first one, is that reversible systems are able to transiently express an object which can then be destructed to express another one for different environmental conditions.

Cooperativity in the integration processes and as part of modulations

The idea of cooperativity is illustrated by many biological systems such as allosteric effects in enzymes, or collective behaviors of ordered mesophases in cellular membranes. The neural connections in brain represent also a source of inspiration for cooperativity at the network level, as they integrate feedback loops and spatial couplings with enhanced information processing. Finally, because of the multiplicity of components in complex supramolecular systems, entropy represents an important drawback for the amplification of the adapted species. Thus, fast kinetic amplification processes are necessary to overcome entropy and disorder. Auto-catalysis and cross-catalysis are for instance important phenomena which can create differential rates of reactions resulting in gradients and thresholds effects.

2. Reaching emergent properties in complex supramolecular systems

A major challenge concerning complex supramolecular systems rests on the combination of all the previously described aspects to benefit of their interplay and to permit the emergence of new properties (including systems' structures and systems' functions).

Diversity

The diversity results from the multiplicity related to the number of components, to the number and nature of interactions they can generate one another, and to the reversiblity of these interactions which allow a full exploration of the combinatorial space.

Selection

The selection results from the specificity of the interactions, from the topology of the reaction networks (random, scale free, hierarchical, with modules, with auto-catalytic pathways, etc.), from the kinetics of diffusion, from the overall reversibility of the system, and from the interactions with the environment which can possibly push open systems far from equilibrium.

Evolution

Supramolecular systems will be ultimately able to evolve if they can generate the components necessary to sustain their own structures, if they can perform mutations in relation to their environment (adaptation), and if they can self-replicate to grow their population.

New functions

Complex supramolecular systems are by essence multi-functional systems which are able to produce several functions from a common set of basic constituents. The expression of these functions can vary in space and time, depending on internal parameters of the systems, and on external pressure of the environment. In addition, emergence of new functions can appear from these systems, although they were not contained within their individual components. This is allowed by numerous synergistic effects in multi-component systems and networks, including allostery, short and long range spatial couplings, compartmentalization, and feedback loops.

Open questions

It is obviously of interest to figure out how far we can push the rules of supramolecular complexity. Because these systems can produce complex hirearchical architectures and are by essence information-gaining far from equilibrium, one might question if the same rules hold up to thinking matter. If it is so, the question of a non-linear rather continuous evolution of these systems will be raised.

3. Using complex supramolecular systems for applications with high societal implications

Supramolecular structures and self-assemblies have already proved their importance in the implementation of new applications for various domains. Their systems counterpart will certainly be of even greater interest for the next generation of smart architectures and devices with multifunctional properties.

Medicine

Supramolecular systems can help in the synthesis of new drugs and imaging agents with better efficiency, for instance by using dynamic combinatorial chemistry to optimize the inhibitor for a given biological target. Other recent complex approaches including enzyme directed evolution and DNA templated approaches will also certainly represent important tools for drug design and diagnostics. One might ultimately imagine the synthesis of pro-drugs which will become active only when necessary in vivo. In addition, drug delivery and transfections, which are often supported by large self-assemblies, are typical problems which will benefit from a system approach.

Cellular and molecular biology

Because of their intrinsic bottom-up constructions, supramolecular systems are crucial to understand how new properties emerge from the percolation of networks. In that sense, systems chemistry is complementary to systems biology which tackles complex problems by a deconvolution approach. Another long standing problem in life science is related to the prediction of protein folding, also based on multiple dynamics of supramolecular interactions. A better fundamental understanding of these phenomena will contribute to solve this problem and to design new biomimetic systems.

Chemistry and materials

Complex structuring and dynamic features of supramolecular systems will be of increasing interest for many new chemical approaches, in particular at the frontier with materials science, a domain with major societal implications. The new generation of smart materials will be necessary responsive, adaptive, multifonctionnal, and possibly self-healing. Systems-based materials can be of importance in the following fields: materials for catalysis, for CO2 capture and water purification, for organic electronics and solar cells, and for information (possibly parallel) processing.

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