Electrostatic, Polar, and steric factors in the Acid Hydrolysis of the Dipeptides

Abstract

Published kinetic data concerning the rates of hydrolysis of dipeptides are discussed and interpreted in terms of the expected electrostatic, polar, and steric influences of the constituent groups. The evidence is consistent with a reaction mechanism in which a proton is first added reversibly to the peptide nitrogen, and the amide cation so formed reacts at the carbonyl carbon atom with a water molecule in a rate-controlling bi molecular substitution. Substitution at the glycyl carbon atom of the parent substance glycylglycine will alter the steric hindrance to substitution by the water molecule. On the other hand, the polar effect of these substituents will be small and will have little influence on the rate of reaction. Substituents at the glycine carbon atom introduce polar factors only with little evidence of steric effects. This absence of a steric effect applies both to the formation of the amide cation and to the substitution by the water. Electron repelling groups decrease the rate of hydrolysis and must be considered to have a greater effect on decreasing the electron accession to the peptide nitrogen necessary for the rupture of the bend than on increasing the concentration of the amide cation. Electron attracting substituents act in the reverse manner. There is some evidence for a small amount of steric compression between groups on either side of the peptide bond for the bimolecular reaction with water.