Ab initio study of the electronic properties of potential antagonists of the glycine receptor: 1. Transition state of the 2‐pyridone · H₂O/2‐hydroxypyridine · H₂O tautomeric equilibrium

Abstract

Glycine receptor substrates are molecules potentially involved in tautomerism phenomena. This study is expected to provide information that might help understand their intrinsic reactivities; such physicochemical data would allow us to establish predictive models in a search for better antagonists. Ab initio molecular orbital studies, using 3-216 and 6 -3 1~* basis sets, are reported for the tautomeric equilibrium of 2-pyridone . H20/2-hydroxypyridine . H20. The geometry of the transition state has also been optimized. The results show the important effect of the water molecule through the formation of hydrogen bonds. This system will be used as a prototype for the design of antagonists of the glycine receptor, a potential site for the action of new antiepileptic drugs and compounds preventing ischemic brain damage. 8