In the Fragrance Business, the Right Molecule Smells like Money

Abstract

Scent is like an image the brain creates from the signals that come from the olfactory receptors in the nasal cavity. It is assumed that the odor molecule interacts noncovalently with the receptor. Odorant recognition by a cognate receptor (or receptors) appears to be determined by a set of molecular features such as individual functional groups or lipophilic surfaces that must obey precise geometric relationships. Smells such as woody, musky, or smoky can be related to a particular chemical structure. Random chemical modification of a lead molecule often yields surprising results. Sometimes completely different molecules are barely discriminated. “With a model at hand, we can sort of predict specific smells.” Margot says.“Humans seem to have between 350 to 380 different receptors,” says Margot, “the evidence gathered so far shows that any chemical will activate a set of receptors. And conversely, any receptor seems to be activated by its characteristic range of chemicals. With these many receptors, you can encode and discriminate hundreds of millions of molecules.”The chemical detection process is just part of the process of smell. The human olfactory pathway is still unknown. The brain converts signals from the nose into an image of a smell. “The long part of that work is the psychophysical characterizations of odor,” Margot says. A shared perceptual pathway could explain why molecules that are structurally different from each other smell the same.Smell is also modulated by adaptation, which may be the reason some people wear too much aftershave. “When you smell a scent at first sniff, it can be quite intense.” Margot said. “If you are continuously exposed to that same scent, your sensitivity decreases. That is adaptation. It seems that when two chemicals are perceived by similar perceptual channels, they crossadapt. One chemical will decrease sensitivity to the other.”The bottom line is that synthesizing a scent molecule on demand is extremely complicated and requires many empirical inputs. “When you synthesize a chemical that has a good smell, you submit it to perfumers, and if they appreciate it too, they study it in different fragrance blends because everything in perfumery depends on mixtures,” Margot says. “Once in the mixture, it often disappears; that means it has no influence on the perceived fragrance. And you don’t know why. It hints to the fact that brain processes could refine the olfactory input at a higher level. All the contributions from the olfactory receptors will be processed in a new message by the brain, and we don’t know how it happens. Amazingly, there are also lucky chemists [who] without knowing about structure-odor relationships, discover something that smells nice by serendipity.”Despite industrial combinatorial chemistry, developing fragrance remains a bit of a black art. “Perfumers have a combination of tremendous memory, skill, and a willingness to experiment.” Turin says, “It took eleven hundred iterations to arrive at the fragrance ‘Tommygirl.’”