Proton transfer from heterocyclic compounds. Part 11. Histidine, histamine, N-acetylhistidine, and histidine-containing peptides

Abstract

Rates of detritiation from the C-2 position of [2-³H]histidine, histamine, and N-acetylhistidine as well as a number of histidine-containing peptides (glycyl-L-histidine, glycyl-L-histidylglycine, β-alanylhistidine, histidylserine, and histidyltyrosine) have been measured over a pH range at 85°. For both histidine and histamine the rate–pH profiles are indicative of hydroxide ion attack on both the protonated and ‘neutral’ species. The magnitude of the rate constant for the second mechanism indicates that the kinetically equivalent zwitterionic form of the substrate also participates in the reaction. The results for N-acetylhistidine can be represented by a bell-shaped rate–pH profile, consistent with hydroxide ion attack on the N-3 protonated species. The results for the other peptides can, to a first approximation, be represented by the same profile, but this may be an over-simplification, resulting from closely similar pK_a values. Electrostatic factors arising from the presence of charged carboxylate and amino-groups close to the C-2 exchanging position are negligible.