Molecular Models for Enzyme Catalysis

Over half a century ago, Pauling [8] formulated the hypothesis that enzymes are molecules that are complementary in structure to the activated complexes (transition states) of the reactions that they catalyse . This view of enzyme catalysis was highly influential and was corroborated by the first structural characterisations of enzyme active sites, which occurred many years later. Today, it is widely recognised that enzyme catalysis involves very specialised molecular recognition, and that this accounts for a major part of the 

In aspirin, the acid catalysis is enhanced by the presence of an intra-molecular hydrogen bond. The H-bond in the salicylate anion is worth 17-21 kJ mol and raises the of the phenolic OH to 13. Other molecular models showed that EMs for intra-molecular general acid-base catalysis can be at least 10 M, if favourable intra-molecular H-bonds are formed [10]. This is also the factor that separates the typical pre-exponential factor of a bimolecular reaction in solution, 10 M sec from that of an intra-molecular reaction between the hydrogen-bonded reactants, 10 sec The basis for this change has been discussed in the context of the intersecting-state model (ISM) applications to proton transfers 

The strength of the hydrogen bonds increases as the static dielectric constant decreases, and this effect is particularly notable when charged species are involved [12]. Additionally, the electrostatic interaction between two atomic charges on the donor and acceptor atoms, 

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Figure 14.10 Molecular models for enzyme catalysis based on cyclodextrins.

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