Spectroscopic and Computational approach for the Structure - Property relationship of Hydantoin drug impurity : 1-methyl-5,5-diphenylimidazolidine-2, 4-dione

1-methyl-5,5-diphenylimidazolidine-2,4-dione (methyl phenytoin) is an intermediate impurity created en-route the commercial manufacture of epileptic drug phenytoin.Ab-initio computational modeling and spectrophotometric techniques are employed to examine molecular geometry and electronic structure to envisage possible structure-activity relationship in 1-methyl-5,5-diphenylimidazolidine-2,4-dione. Comparative studies show satisfactory consilience between theoretical and experimental approaches. According to DFT studies, the molecules are visualized to dimerize via hydrogen bonding. The two phenyl rings are not coplanar as evidenced by the dihedral angles between benzene rings and imidazole ring. The extent of intermolecular hydrogen bonding has been reduced due to methyl substitution at N1 and this assumes importance as anticonvulsant property is directly proportional to the extent of hydrogen bonding. A relatively high HOMO-LUMO energy gap of 5.9 eV implies good thermodynamical stability and a prospect of impurity being carried over during commercial drug manufacturing.Further, the presence of methyl substitution closer to the bio-toxic face opens up a prospect of title molecule being studied as an alternate drug with marked anti-epileptic action and less or no toxicity. (paper)