A semiempirical theoretical study of the molecular interaction of cocaine with the biological substrate glycine

Semiempirical SCFMO computations of the MNDO and AM1 varieties have been employed to model possible interaction processes for cocaine with the biological substrate glycine. It was found for the gas‐phase species that the most likely interactions occurred as nucleophilic attack of the nitrogen lone pair of glycine on the two carbonyl groups of cocaine. These reactions led to intermediates which further decomposed exothermically to amide and alcohol species. The activation enthalpies for the gas‐phase reactions were predicted to be high (39–46 kcal/mol), but it is believed that such processes could possibly occur by reaction pathways with considerably lower activation energies in the liquid state in the presence of mucus containing olfactory binding protein in vertebrate olfactory reception.