Perturbational Effects of Lithium Cation on Phenytoin Tautomers

Phenytoin is a long-standing, anti-seizure drug used in the treatment of epilepsy, however it has been classified as possibly carcinogenic to humans. It may exhibit 1,3- and 1,5-type proton tautomerism. In the present study, within the constraints of density functional theory at the level of B3LYP/6-31++G(d,p), tautomerism of phenytoin has been investigated. The obtained data collected for vacuum as well as aqueous conditions indicated that the equilibrium concentration of the enol type tautomer should be low. On the other hand, lithium is often referred as an antimaniac drug and used clinically to prevent mood swings in patients with bipolar effective disorder. The present study also considers the mutual interaction of lithium cation and phenytoin at the molecular level. Both the unperturbed and perturbed (by lithium cation) phenytoin tautomers have exothermic heat of formation values and favorable Gibbs free energy of formation values. They are electronically stable. Various quantum chemical data for the unperturbed and perturbed tautomers of phenytoin have been collected and discussed.