Solvent Effects on the Structure-Property Relationship of Some Potentially Pharmacologically Active 3-(4-Substituted Benzyl)-5-Ethyl-5-Phenyl- and 3-(4-Substituted Benzyl)-5,5-Diphenylhydantoins

Abstract

Two series of 3-(4-substituted benzyl)-5-ethyl-5-phenyl- and 3-(4-substituted benzyl)-5,5-diphenylhydantoins were synthesized and their UV absorption spectra were recorded in the region 200-400 nm in selected solvents of different polarity. The effects of solvent dipolarity/polarizability and solvent/solute hydrogen bonding interactions on the spectral shifts were analyzed by means of the linear solvation energy relationship (LSER) methodology of Kamlet and Taft. The quantitative relationships between hydrogen bonding interactions and the lipophilicity and blood-brain permeation of the studied compounds were discussed. Satisfactory linear dependences were obtained for moderate electron-donating and electron-withdrawing substituents at the benzyl moiety, while the strong electron-withdrawing substituent (NO2) significantly modifies the solvation characteristics of the molecule. The paper clearly demonstrates how the solvatochromic comparison method may be applied to estimate the contributions of various modes of solvation to the pharmaceutically relevant properties of these newly synthetized hydantoin derivatives.