Formation of amino acid derived 2-thiohydantoins - An experimental and theoretical study

Abstract

Hydantoins and thiohydantoins derived from amino acids are an interesting subset of compounds that have a wide range of chemical and biological properties. The chemistry of amino acid derived hydantoins does not require rigorous conditions and thus, their formation is plausible in physiological conditions. Hydantoins have been isolated from urine in cases where protein consumption is increased. This raises a question of chemical and biological implications of their presence and, accordingly, elucidation of mechanisms trough which they are formed gains importance. The reaction of 2-thiohydantoin formation from corresponding amino acids was monitored by 1H NMR spectroscopy and rate constants were determined. The mechanism of the reaction was examined using the M06-2X/6-311++G(d,p) theoretical model. The calculated rate constants of the reaction and the observed rate constants determined using NMR spectroscopy are in a good accordance. On the basis of the theoretical calculations, a different mechanism from the previously reported is proposed.