Molecular orbital approach to possible discrimination of musk odor intensity

Despite the recent progress in molecular biology of odor receptors, codes o f olfactory molecules, which provide information on odor discrimination, st ill remain to be elucidated. Musk molecules are known to have a wide variet y of chemical structures. To find the reactive sites of musk molecules, we analyzed electronic localization of 203 musk-related molecules including 13 9 musks and 64 nonmusks by Computer-Aided Chemistry Programs (CAChe Program s) with PM3 parameters. The relationship between electronic localization an d odor intensities of musk-related molecules was studied by discriminative function analysis and multiple regression analysis. We found reactive sites with high values of electrophilic frontier densities (EFDs) at appointed p ositions in musk molecules. EFD is a theoretical index that predicts reacti ve sites acting as electron donors. Changes in values of EFDs at these posi tions not only distinguish musks from nonmusks but are also precisely corre lated with intensity levels of musk odor. The result indicates that musk mo lecules have common reactive sites that play a critical role in the interac tion with a receptor. Changes in reactivities of these sites correlate with musk odor intensities subjectively judged by perfumers, indicating that hu man discrimination of musk odor is determined at the stage of interaction b etween musk molecules and an odor receptor. (C) 2000 John Wiley & Sons, Inc .