Theoretical studies on Schiff base formation of vitamin b6 analogues

Abstract

A comprehensive study of Schiff base formation of vitamin b6 analogues in gas-phase and water solvation environment is carried out using semiempirical (PM3) quantum mechanics calculations. Vitamin b6 analogues for the gas-phase calculations include one auxiliary water molecule whilst water solvation has been taken into account by using two different models: continuum solvation model on the gas-phase optimized structures and supermolecular approach, in which a complete reoptimization of the gas-phase structures surrounded with explicit water molecules is performed. These calculations result in the description of the geometries of all the intermediates and transition structures along the reaction pathway, which can be divided in three parts: carbinolamine formation, dehydration and imine formation. The carbinolamine is the main intermediate and dehydration is the limiting step of the reaction, in accordance with experimental evidence. The details of the mechanism highlight the key role of internal hydrogen transfers and of the hydrogen bonds from water molecules of the solvation sphere for the occurrence of the reaction.