Supramolecular reactivity and catalysis

The design of highly efficient and selective reagents and catalysts is one of the major goals of research in chemistry, the science of matter and of its transformations. 

The particularly remarkable features displayed in this respect by the natural catalysts, the enzymes, has provided major stimulus and inspiration for the development of novel catalysts by either manipulating the natural versions or by trying to devise entirely artificial catalysts that would nevertheless display similar high efficiencies and selectivities. In his Nobel award lecture in 1902, Emil Fischer has shown remarkable prescience when he said / can foresee a time in which physiological chemistry will not only make greater use of natural enzymes but will actually resort to creating synthetic ones [5.1]. 

Supramolecular reactivity and catalysis thus involve two main steps binding, which selects the substrate, and transformation of the bound species into products within the supermolecule formed. Both steps take part in the molecular recognition of the productive substrate and require the correct molecular information in the reactive receptor. Compared to molecular reactivity, a binding step is involved that precedes the reaction itself. Catalysis additionally comprises a third step, the release of the substrate. 

The selection of the substrate is not the only function of the binding step. In order to promote a given reaction, the binding should strain the substrate [5.2] so as to bring it toward the transition state of the reaction thus, efficient catalysts should 

One must note that in a number of cases the processes described amount to facilitation of a given reaction in a catalytic cycle but not to full catalysis, due to slow regeneration steps, product inhibition, etc. The term catalysis will be applied to examples mentioned below with this restriction in mind. 

---

The systems described in this chapter possess properties that define supramolecular reactivity and catalysis substrate recognition, reaction within the supermolecule, rate acceleration, inhibition by competitively bound species, structural and chiral selectivity, and catalytic turnover. Many other types of processes may be imagined. In particular, the transacylation reactions mentioned above operate on activated esters as substrates, but the hydrolysis of unactivated esters and especially of amides under biological conditions, presents a challenge [5.77] that chemistry has met in enzymes but not yet in abiotic supramolecular catalysts. However, metal complexes have been found to activate markedly amide hydrolysis [5.48, 5.58a]. Of great interest is the development of supramolecular catalysts performing synthetic... 

The principles of supramolecular catalysis relate to enzyme catalysis, because weak chemical bonds involving well defined hydrogen bonds are essential. Lehnl formulated two main steps required for supramolecular reactivity and catalysis ... 

Supramolecular control of reactivity and catalysis is among the most important functions in supramolecular chemistry. Since catalysis arises from a differential binding between transition and reactant states, a supramolecular catalyst is, in essence, chemical machinery in which a fraction of the available binding energy arising from noncovalent interactions is utilized for specific stabilization of the transition state or, in other words, is transformed into catalysis. 

In this chapter we focus on supramolecular chemical reactivity. In particular this means predominantly the role supramolecular chemistry plays in accelerating or understanding chemical reactions. There are close parallels between artificial, abiotic supramolecular reactivity and biochemistry, for example in the study of enzymes, Nature s catalysts - described in Section 2.6. Synthetic catalysts can both model natural ones and allow the design of new, different kinds of reactions. Supramolecular catalysis sits somewhere between chemical catalysis (transition metal and organocatalysis) and biology. Some considerations within various kinds of catalysis are summed up in the chart shown in Figure 12.1. 

Di Stefano S, Cacciapaglia R, Mandolini L. Supramolecular control of reactivity and catalysis — effective molarities of recognition-mediated bimolecular reactions. Eur J Org Chem. 2014 7304-7315. 

J. Am. Chem. Soc., 126, 16280-16281 Zelder, F.H. and Rebek, J. Jr. (2006) Cavitand templated catalysis of acetylcholine. Chem. Commun., 753-754 Purse, B.W. and Rebek, J. Jr. (2005) Supramolecular structure and dynamics special feature Functional cavitands Chemical reactivity in structured environments. Proc. Nail. Acad. Sci. U.S.A., 102, 10777-10782. 

Transition metal polypyridine complexes are highly redox-active, both in their electronic ground- and excited states. Their electron transfer reactivity and properties can be fine-tuned by variations in the molecular structure and composition. They are excellent candidates for applications in redox-catalysis and photocatalysis, conversion of light energy into chemical or electrical energy, as sensors, active components of functional supramolecular assemblies, and molecular electronic and photonic devices. 

One particular asset of structured self-assemblies is their ability to create nano- to microsized domains, snch as cavities, that could be exploited for chemical synthesis and catalysis. Many kinds of organized self-assemblies have been proved to act as efficient nanoreactors, and several chapters of this book discnss some of them such as small discrete supramolecular vessels (Chapter Reactivity In Nanoscale Vessels, Supramolecular Reactivity), dendrimers (Chapter Supramolecular Dendrlmer Chemistry, Soft Matter), or protein cages and virus capsids (Chapter Viruses as Self-Assembled Templates, Self-Processes). In this chapter, we focus on larger and softer self-assembled structures such as micelles, vesicles, liquid crystals (LCs), or gels, which are made of surfactants, block copolymers, or amphiphilic peptides. In addition, only the systems that present a high kinetic lability (i.e., dynamic) of their aggregated building blocks are considered more static objects such as most of polymersomes and molecularly imprinted polymers are discussed elsewhere (Chapters Assembly of Block Copolymers and Molecularly Imprinted Polymers, Soft Matter, respectively). Finally, for each of these dynamic systems, we describe their functional properties with respect to their potential for the promotion and catalysis of molecular and biomolecu-lar transformations, polymerization, self-replication, metal colloid formation, and mineralization processes. 

Endowing these polymolecular entities with recognition units and reactive functional groups may lead to systems performing molecular recognition or supramolecular catalysis on external or internal surfaces of organic (molecular layers, membranes, vesicles, polymers, etc.) [7.1-7.13, A.41] or inorganic (zeolites, clays, sol-gel preparations, etc.) [7.14-7.20] materials. 

One may imagine extending this type of methodology to reactivity, catalysis and transport by generating suitable libraries for the discovery of novel synthetic reagents, reactions, catalysts [9.176c] and carriers as well as for the exploration of product preparation through supramolecular assistance to synthesis (see Section 9.6). 

Supramolecular catalysis can involve passive effects such as the confining of two reactive molecules within a cavity and active effects where the catalyst interacts with the substrate via an active site. The active site may be metal-based as in other kinds of homogeneous catalyst based on transition metals or Lewis acids, or my involve interactions such as hydrogen bonding to bring about both polarisation of the reactants and their mutual spatial organisation. 

---