Effects of α-amino acids and small peptides on the rate of an S_N1 acetal hydrolysis reaction in aqueous solution: the interplay of hydrophobic and hydrophilic solute hydration

Abstract

The effects of small amounts of anionic α-amino acids and several small peptides on the kinetics of the S_N1 hydrolysis of 2-(4-nitrophenoxy)tetrahydropyran have been investigated at pH 11 and 40 °C. The rate-retarding effect at 1 molal of cosolute is plotted as ln (k_{m = 1}/k_{m = 0}) versus the number of CH groups in the amino acid side chain. Linear correlations are observed for small α-amino acids from Gly up to Pro. Additivity is also obtained for longer alkyl chains with n(CH) > 6, but these retarding effects of the CH groups are larger and comparable to the CH group contribution obtained for short-chain primary alcohols. The kinetic effects of isomeric aliphatic α-amino acids with linear and branched side chains are compared and show non-additivity. The results are interpreted in terms of the hydrophobicity of CH groups inside and outside the hydrophilic hydration spheres of the polar groups of the α-amino acid. Amino acids with aromatic side chains do not fit in the additivity pattern, probably due to their more pronounced hydrophobicity.Kinetic data for two isomeric dipeptides, Gly-Val and Val-Gly, are also rationalised in terms of intramolecular hydration shell overlap and show the interplay of hydrophobic and electrostatic interactions. The effects of glycine oligomers, (Gly)_n (n = 2, 3, 4), reveal the complexity of the hydration of multi-functional molecules. The results are relevant in the context of understanding molecular recognition processes involving enzymes and proteins in aqueous solution.

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