DFT studies on Schiff base formation of vitamin B6 analogues

A comprehensive study of Schiff base formation of vitamin B-6 analogues by using DFT calculations (B3LYP/ 6-31+G*) and a study of the topology of the density charge function of the optimized structures according to Bader's AIM theory are carried out. Vitamin B6 analogues for the gas-phase calculations include one auxiliary water molecule. 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 of carbinolamine formation highlights the key role of the auxiliary water molecule of the molecular complex as a true reactive for allowing the nucleophilic attack of the incoming amine to the carbonyl group.