Molecular Pharmacology, Vol 10, 48-56, Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics

Characteristics of the Hydrogen Bonding Interactions of Substituted Hydantoins with 9-Ethyladenine

¹ Department of Pharmacology, University of Utah, Salt Lake City, Utah 84112

Specific binding of diphenylhydantoin and other substituted hydantoins to 9-ethyladenine was demonstrated using proton magnetic resonance and infrared spectroscopy. Downfield resonance shifts of the N-1 and N-3 protons of diphenylhydantoin occurred upon mixing with 9-ethyladenine in dimethyl sulfoxide, whereas no such resonance shift occurred upon the addition of 9-ethylguanine in this solvent. Chemical shifts of the exchangeable protons in deuterochloroform solutions of 9-ethyladenine with 1,5,5-trimethylhydantoin or 3,5,5-trimethylhydantoin are characteristic of a hydrogen-bonded cyclic interaction; this interaction involves one of the three -NH-CO-sites available on the hydantoin nucleus in a 1:1 complex with the acceptor-donor sites on 9-ethyladenine. By measuring the change in intensity of the adenine NH (antisymmetrical) monomer band in the normal infrared region, association constants [K_xy, M^-1] were estimated for the interaction (in deuterochloroform) of 9-ethyladenine with the given hydantoin: 5,5-dimethylhydantoin, 63; 1,5,5-trimethylhydantoin, 16; 3,5,5-trimethylhydantoin, 2.7; 5,5-diphenylhydantoin, 178; 5-ethyl-1-methyl-5-phenylhydantoin, 179; 5-ethyl-3-methyl-5-phenylhydantoin, 5.4; 3-ethyl-5-phenylhydantoin, 2.6; and 3-methyl-5,5-diphenylhydantoin, 5.1.

Note:
ACKNOWLEDGMENTS We thank Dr. A. D. Broom and R. Snow for their assistance with the NMR spectroscopy, and Dr. Donald J. Lyman for making available for our use the Perkin-Elmer 521 infrared spectrophotometer.