Binding of protons and zinc ions to transition states for tautomerization of α-heterocyclic ketones: implications for enzymatic reactions
✍ Scribed by Stephen J. Eustace; Geraldine M. McCann; Rory A. More O'Ferrall; Michael G. Murphy; Brian A. Murray; Sinead M. Walsh
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 145 KB
- Volume
- 11
- Category
- Article
- ISSN
- 0894-3230
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✦ Synopsis
The description of catalysis in terms of binding of a catalyst to the transition state propoposed by Kurz is applied to tautomerization of the a-heterocyclic ketones phenacylpyridine, phenacylpyrazine, phenacylphenanthroline and phenylacetylpyridine catalysed by protons and zinc ions. Binding constants for protonated and zinccoordinated transition states, K B ≠ are reported and Brønsted coefficients are calculated from comparison of K B ≠ with binding constants for the keto reactant and enolate anion intermediate. The formal equivalence of the binding formalism to a conventional Brønsted analysis is emphasized, and the results are compared with those from a 'generalised' Brønsted plot of rate constants against equilibrium constants for reactions of uncomplexed, protonated and zinc ion-coordinated ketones. This plot confirms that intrinsic reactivities of metal-coordinated and protonated substrates are similar even where differences exist between substrates. Application of a comparable Kurz-Brønsted treatment to enzymatic reactions depends in principle upon (a) dissecting binding contributions to catalysis from approximation of covalently reacting groups and (b) separating binding at the reaction site of the substrate, to which Kurz's treatment applies, from 'remote' binding, which, to a first approximation, is unchanged between Michaelis complex and transition state. The Brønsted relationship highlights stabilization of reactive intermediates as a thermodynamic driving force for binding catalysis at the reaction site. A formal expression which describes this stabilization, and also accommodates stabilization by remote binding of the substrate and intermediate by the enzyme, is proposed. Its relationship to the usual expression for application of the Kurz approach to enzyme catalysis, (k cat /k 0 )/ K m = K B ≠ , is discussed and the usefulness of the Brønsted and Marcus relationships for interpreting K B ≠ is emphasized.