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The complex interplay between systems and their environment plays an important role in processes ranging from self-assembly to evolution. Polymorphism, where, from the same ingredients different products can be formed, is likely to be an important enabler for evolutionary adaptation. Environmental pressures may induce polymorphic behaviour, where different pressures result in different structural organisation. Here we show that by combining covalent and non-covalent bond formation three distinct polymorphs can emerge from the same small dynamic molecular network: vesicular aggregates, self-replicating fibres and nanoribbons, depending on the nature of the solvent environment. Additionally, a particular set of conditions allows the transient co-existence of both vesicles and fibres.

Building on our ability to design and synthesise molecules and our understanding of the noncovalent interactions between these molecules, the chemical sciences are currently entering the new territory of Systems Chemistry. This young field aims to develop complex molecular systems showing emergent properties; i.e. properties that go beyond the sum of the characteristics of the individual consituents of the system. This review gives an impression of the state of the art of the field by showing a diverse number of recent highlights, including out-of-equilibrium self-assembly, chemically fuelled molecular motion, compartmentalised chemical networks and designed oscillators. Subsequently a number of current challenges related to the design of complex chemical systems are discussed, including those of creating concurrent formation-destruction systems, continuously maintaining chemical systems away from equilibrium, incorporating feedback loops and pushing replication chemistry away from equilibrium. Finally, the prospects for Systems Chemistry are discussed including the tantalizing vision of the de novo synthesis of life and the idea of self-synthesising and self-repairing chemical factories.

The study of complex mixtures of interacting synthetic molecules has historically not received much attention from chemists, even though research into complexity is well established in the neighbouring fields. However, with the huge recent interest in systems biology and the availability of modern analytical techniques this situation is likely to change. In this tutorial review we discuss some of the incentives for developing systems chemistry and we highlight the pioneering work in which molecular networks are making a splash. A distinction is made between networks under thermodynamic and kinetic control. The former include dynamic combinatorial libraries while the latter involve pseudo-dynamic combinatorial libraries, oscillating reactions and networks of autocatalytic and replicating compounds. These studies provide fundamental insights into the organisational principles of molecular networks and how these give rise to emergent properties such as amplification and feedback loops, and may eventually shed light on the origin of life. The knowledge obtained from the study of molecular networks should ultimately enable us to engineer new systems with properties and functions unlike any conventional materials.

Three building blocks of general structure (MeO)2CH–aromatic linker–Pro–amino acid–NHNH2 have been prepared and tested in acid-catalysed dynamic combinatorial libraries. Exposure of these libraries to LiI and NaI led to the amplification of three macrocyclic pseudopeptide receptors. The receptors were isolated and their interactions with LiI and NaI were analysed using NMR, IR and ITC. Binding of the metal ions to the receptors is invariably entropy-driven. Nevertheless, all receptors were found to be flexible with substantial conformational rearrangements accompanying guest binding. This type of receptor is extremely difficult to access through rational design and the fact that dynamic combinatorial chemistry allows facile access to these challenging molecules underlines the power of the dynamic approach.

Few methods currently exist for controlling vesicle-vesicle adhesion. We now report a new system, based upon a multivalent guest and an amphiphilic receptor with a photo-isomerisable anchor that can be incorporated into lipid vesicles of different sizes. Large unilamellar vesicles containing our receptor were found to aggregate upon addition of the multivalent guest, independently of photoswitching between the two conformations of the anchor. However, for giant vesicles immobilised on a platinum wire, guest-mediated adhesion only occurred upon photo-isomerisation of the anchor. This behaviour was attributed to the dynamics introduced into the system through the conformational changes caused by irradiation.

A transition-state analogue (TSA) for an acetal hydrolysis reaction was found to select and amplify a macrocycle from a dynamic combinatorial library (DCL) of disulfides in water. This host was able to accelerate the reaction by a factor of two; a similar value was progressively reached when the macrocycle was gradually produced in the course of the reaction.