A nitrogen-15 nuclear magnetic resonance study of the acid-base and tautomeric equilibriums of 4-substituted imidazoles and its relevance to the catalytic mechanism of α-lytic protease

Abstract

The pH dependence of the ^(15)N NMR shifts of histamine, imidazole-4-propionic acid, imidazole-4-acetic acid, trans and cis-urocanic acid, and endo-cis-3-(4-imidazoyl)bicyclo[2.2.h1]e pt-5-ene-2-carboxylic acid has been determined at the natural-abundance level of ^(15)N. The chemical-shift changes permit calculation of pK_a values for the acidic species present as well as reasonably accurate positions of the Nl(H)⇌N3(H) tautomeric equilibria for those species having unprotonated imidazole rings. The ^(15)N shifts of cis-urocanic acid and endo-cis-3-(4-imidazoyl)bicyclo [2.2.1] hept-5-ene-2-carboxylic acid demonstrate that carboxylate-N3(H) hydrogen-bonding interactions can cause the N3(H) tautomers to be substantially more stable than the Nl(H) tautomers. The unusual positions of these tautomeric equilibria are quite similar to that found for the histidine of the catalytic triad of α-lytic protease.

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