Transition state stabilisation

Intermediate 1 could also be stabilised by proton transfer from oxygen to give 3 in Scheme 11.9. The proton acceptor B could be solvent water or a general base catalyst. The reaction will only be catalysed if the rate of breakdown of 1 to regenerate reactants is faster than the rate of proton transfer. In this case, such catalysis would be independent of the base strength of the catalyst B as proton transfer would invariably be thermodynamically favourable and hence occur at the maximum diffusion-controlled rate. If proton transfer to solvent is thermodynamically favourable, such that proton donation to 55.5 M water is faster than to, say, 1 M added base, any observed catalysis by base must represent transition state stabilisation by hydrogen bonding, or a concerted mechanism. 

This relevant finding is attributed to the greater nucleophilic discrimination factor of DMSO in its complex, whereas the trans effect is attributed to transition-state stabilisation arising from the x-acceptor properties of the ligand, S-bound DMSO being considered a better o-donor and x-acceptor than ethylene (22). 

A Chapter on biocatalysis is not really complete without introducing the idea of transition state theory and the concept of transition state stabilisation as the most fundamental means in biocatalysis for biocatalysts to effect rate enhancements. 

As a result of this importance, great efforts have been made to understand the interplay between structure and chemistry to produce optimised acid catalysts for processes such as cracking, alkylation and isomerisation. It is now well established that zeolites are not superacidic, so that the apparent carbenium ion controlled conversions are thought to pass through carbenium-ion-like transition states stabilised by the zeolite framework. For methanol-to-hydrocarbon reactions, elegant in situ NMR has demonstrated that a reactive hydrocarbon pool that forms within the pores is observed to be responsible for the formation of the first C-C bonds, and it is likely that reactive hydrocarbon intermediates have a greater role in add-catalysed reactions than previously spelt out. 

This catalysis is probably a combination of transition state stabilisation by the intact active site, as well as general base catalysis by the other active site glutamate, enhancing the nucleophUicity of the acceptor. It is posmlated [35] that the mutant serine residue stabilises the glycosylation transition state by neutralising... 

While selection for RNA aptamers that bind transition state analogues have not yet yielded catalysts, researchers have found many RNAs that specifically bind amino acids [21], as well as other small molecules. It seems possible that RNAs that bind amino acids, for example, may have evolved to catalyse peptide bond formation. Subtle mutations that conferred less binding to reactants or products may have led to transition state stabilisation and subsequent product formation. As enzymes (nucleic acid or otherwise) developed diverse catalytic strategies, biological complexity would have increased. 

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