Organic Chemistry Seminar

Our sense of smell plays a central role in our interaction with the world around us. We can detect a vast number of individual and mixed odorants of diverse structure, informing our selection and enjoyment of food, alerting us to hazards, and even guiding our choice of a mate. In exploring the molecular basis of mammalian olfaction I select from both the worst- and best-smelling odorants: thiols and musks. While the vibration theory of olfaction (VTO) proposes that the unique thiol IR absorption at 2500 cm-1 is responsible for their characteristic odor, our work establishes that ionic copper plays a key role in the binding of sulfur compounds to mammalian olfactory receptors (ORs). While the VTO argues that deuterated compounds have different odors than their non-deuterated counterparts, our work using deuterated musks establishes that there is no difference in the binding of deuterated and non-deuterated odorants to ORs. We propose that the molecular basis of olfaction can best be explained by the docking theory of olfaction, involving weak noncovalent electrostatic, van der Waals, H-bonding, dipole−dipole, pi–pi, metal ion, pi-cation, and hydrophobic odorant-receptor interactions.