HYDROLYSIS OF PEPTIDE BONDS BY INTRAMOLECULAR PARTICIPATION OF BENZIMIDAZOLIUM IONS

A series of 5,7-dinitrobenzimidazolyl-4 peptides have been prepared and the rates of hydrolysis of the peptide bond determined as a function of acidity and temperature. It is demonstrated that the rate of hydrolysis is dependent on the degree of protonation of a benzimidazole nitrogen atom. The effectiveness of the intramolecular participation varies with the nature of the peptide side chain and with the degree of alkylation of the imidazole ring. No correlation is observed between pKa and specific rate constant for the various substrates. Heats of ionization and activation parameters are reported for two cases. The compound, 1,2-dimethyl-5,7-dinitrobenzimidazolyl-4-alanylglycine, was found to hydrolyze 65,000 times as rapidly as 2,4-dinitrophenylalanylglycine. © 1969, American Chemical Society. All rights reserved.