Affiliation:
1. Department of Chemistry, Middle East Technical University, Üniversiteler, Eskişehir Yolu No: 1, 06800 Çankaya/Ankara, Turkey
Abstract
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.
Reference47 articles.
1. Windholz, M., & Budavari, S. (Eds.) (1983). The Merck Index (10th ed). Rahway, USA: Merck & Co. Inc.
2. Katzung, B.G. (1984). Basic and clinical pharmacology. Lange Medical Pub.
3. Dreifus, L.S., & Watanabe, Y. (1970). Current status of diphenylhydantoin. American Heart Journal, 80, 709-713. https://doi.org/10.1016/0002-8703(70)90018-9
4. Zeng, K., Wang, X., Xi, Z., & Yan, Y. (2010). Adverse effects of carbamazepine, phenytoin, valproate and lamotrigine monotherapy in epileptic adult Chinese patients. Clinical Neurology and Neurosurgery, 112(4), 291-295. https://doi.org/10.1016/j.clineuro.2009.12.014
5. Patocka, J., Wu, Q., Nepovimova, E., & Kuca, K. (2020). Phenytoin - An anti-seizure drug: Overview of its chemistry, pharmacology and toxicology. Food and Chemical Toxicology, 142, 111393. https://doi.org/10.1016/j.fct.2020.111393