Metal ion – biomolecule interactions. Part 14. Methylmercury and hydrogen ion catalysis of C(2)-H isotopic exchange in 1-methylhistidine

Abstract

The rate constants for detritiation from the C(2) position of 1-methyl[2-3H]histidine have been determined in a series of aqueous buffers at 85 °C. The resulting sigmoidal rate–pH profile was indicative of a mechanism involving hydroxide ion attack on the N(3)-protonated (4) and the amino-protonated (5) forms of 1-methylhistidine, and dissection of the kinetic data allowed the extraction of the second-order rate constants for the two pathways, k and k′. The unusually large value of k′ for a species not protonated at N(3) of the imidazole ring suggested the involvement of a kinetically equivalent zwitterionic form of the substrate (7). Comparison of the rate constant k with values determined previously for closely related substrates, such as histidine, 1-methylimidazole, and imidazole, led to the use of FMO theory to explain the effect of the various structural changes, e.g., the effect of methylation and a positively charged side chain on k and k′. The addition of MeHgNO3 resulted in a decrease in the pseudo-first-order rate constant for detritiation. The rate retardation was discussed in terms of two mechanisms (Schemes 2 and 3). Analysis of the data in terms of the various metal-ion-coordinated species present under the experimental conditions showed that the reactivity of the protonated substrate greatly exceeds that of the metal-coordinated species. The difference in the catalytic ability of H+ vs. MeHg+ is discussed in terms of the extent of positive charge developed on the ligating heteroatom in the ylide (carbenoid) reaction intermediate. Keywords: methylmercury, 1-methylhistidine, isotopic exchange, proton transfer, metal ion catalysis.