Supramolecular catalysis

Supramolecular catalysis refers to an application of supramolecular chemistry, especially molecular recognition and guest binding, toward catalysis. This field precedented by enzymatic system which, unlike classical organic chemistry reactions, utilizes non-covalent interactions such as hydrogen bonding, cation-pi interaction, and hydrophobic forces to accelerate reaction and/or enhanced selectivity . Because enzymes are structurally complex and difficult to modify, supramolecular catalysts offer a potentially simpler model for studying factors involved in catalytic efficiency of the enzyme. Another goal that motivates this field is the development of efficient and practical catalysts that may or may not have an enzyme equivalent in nature. While supramolecular forces no doubt influence many catalytic processes, especially in asymmetric catalysis, none of the examples below has achieved commercialization.

History

The term supramolecular chemistry is defined by Jean-Marie Lehn as "the chemistry of intermolecular bond, covering structures and functions of the entities formed by association of two or more chemical species" in his Nobel lecture in 1987. The concept of supramolecular catalysis was started way earlier in 1946 by Linus Pauling when he founded the theory of enzymatic catalysis in which rate acceleration is the result of non-covalent stabilization of the transition state by the enzymes. Nevertheless, it was not until a few decades later that an artificial enzyme was developed. Early enzyme mimics were based on crown ether and cryptand. In 1976, less than ten years after the discovery of crown ether, Cram et al. developed a functionalized binapthyl crown ether that catalyze transacylation. The catalyst makes use the crown ether motif's ability to capture cation to bind to the ammonium ion part of the substrate and subsequently employs the nearby thiol motif to cleave the ester. From the early 1970s, cyclodextrins have been extensively studied for its encapsulation properties and used as binding sites in supramolecular catalyst. Cyclodextrins have rigid ring structure, hydrophilic surface, and hydrophobic cavity on the inside; therefore, they are capable of binding organic molecules in aqueous solution. In 1978, with the background knowledge that the hydrolysis of m-tert-butylphenyl acetate is accelerated in the presence of 2-benzimidazoleacetic acid and alpha-cyclodextrin, Brewslow et al. developed a catalyst based on a beta-cyclodextrin carrying two imidazole groups. This cyclodextrin catalytic system mimics ribonuclease A by its use of a neutral imidazole and an imidazolium cation to selective cleave cyclic phosphate substrates. The rate of the reaction is catalyzed 120 times faster, and unlike a hydrolysis by simple base NaOH that gives a 1:1 mixture of the products, this catalysts yield a 99:1 selectivity for one compound. 1993 witness the first self-assembled capsule and in 1997 the so-called "tennis ball" structure was used to catalyze a Diels-Alder reaction. Self-assembled molecules have an advantage over crown ether and cyclodextrin in that they can capture significant larger molecules or even two molecules at the same time. In the following decades, many research groups, such as Makoto Fujita, Ken Raymond, and Jonathan Nitschke, developed cage-like catalysts also from molecular self-assembly principle. In 2002, Sanders and coworkers published the use of dynamic combinatorial library technique to construct a receptor and in 2003 they employed the technique to develop a catalyst for Diels-Alder reaction.

Mechanism of catalysis

Orienting reactive and labile groups

A supramolecular host could bind to a guest molecule in such a way that the guest's labile group is positioned close to the reactive group of another reactive species. The proximity of the two groups enhances the probability that the reaction could occur and thus the reaction rate is increased. This concept is similar to the principle of preorganization which states that complexation could be improved if the binding motifs are preorganized in a well-defined position so that the host does not require any major conformational change for complexation. In this case, the catalyst is preorganized such that no major conformational changes is required for the reaction to occur. A notable example of catalysts that employ this mechanism is Jean-Marie Lehn's crown ether. In addition, catalysts based on functionalized cyclodextrins often employ this mode of catalysis.

Raising the effective substrate concentration Bimolecular reactions are highly dependent on the concentration of substrates. Therefore, when a supramolecular container encapsulates both reactants within its small cavity, the effective local concentration of the reactants is increased and, as a result of an entropic effect, the rate of the reaction is accelerated. That is to say an intramolecular reaction is faster than its corresponding intermolecular reaction. Although high raise in effective concentration is observed, molecules that employ this mode of catalysis have tiny rate acceleration compared to that of enzymes. A proposed explanation is that in a container the substrates are not as tightly bound as in enzyme. The reagents have room to wiggle in a cavity and so the entropic effect might not be as important. Even in the case of enzymes, computational studies have shown that the entropic effect might also be overestimated. Examples of molecules that work via this mechanism are Rebek's tennis ball and Fujita's octahedral complex.

Stabilizing transition state

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