Solvent Effects on the Structure-Activity Relationship of Phenytoin-like Anticonvulsant Drugs

Abstract

The absorption spectra of nine compounds structurally related to phenytoin (5,5-diphenylhydantoin) were recorded in twelve solvents over the range of 200 to 400 nm. The effects of solvent dipolarity/polarizability and solvent/solute hydrogen bonding interactions were analyzed by means of the linear solvation energy relationship (LSER) concept proposed by Kamlet and Taft. The lipophilic activity of the investigated hydantoins was estimated by calculation of their log (10) P values. The calculated values of log (10) P were correlated with the ratio of the contributions of specific and non-specific solute/solvent interactions. The correlation equations were combined with the corresponding ED50 values to generate new equations that demonstrate exact relationship between solute/solvent interactions and the structure-activity parameters.