Molecular complexity determines the number of olfactory notes and the pleasantness of smells

International audienceOne major unresolved problem in olfaction research is to relate the percept to the molecular structure of stimuli. The present study examined this issue and showed for the first time a quantitative structure-odor relationship in which the more structurally complex a monomolecular odorant, the more numerous the olfactory notes it evokes. Low-complexity odorants were also rated as more aversive, reflecting the fact that low molecular complexity may serve as a warning cue for the olfactory system. Taken together, these findings suggest that molecular complexity provides a framework to explain the subjective experience of smells. T he wealth of our sensory world relies on the diversity of stimuli in our environment and on their manifold effects on behavior and cognition. The physical properties of stimuli are predictive of perception: perceived colors rely on the integration of frequencies of light waves in the visual system, and the pitch of a sound is perceived as high or low depending on its acoustic frequency. As regards smell, however, the relation between percept and stimulus properties remains unclear. Olfactory perception is based on binding between ligands (odorant molecules) and olfactory receptors which are thought to recognize specific molecular features. An important rule governing this interaction is that a given odorant can activate one or several olfactory receptors 1. This combinatorial coding is then processed by higher brain structures and gives rise to percepts that are difficult to name for novices but are sensed by experts in perfumery as olfactory ''notes'' (a smell being described as ''green'', ''woody'', ''tobacco'', etc). For example, whereas some odors are described by few olfactory notes (e.g., furan is described as smokey, cinnamon-like and spicy), others are described by multiple notes (e.g., coumarin is described as herbaceous, sweet, spicy, nut-like, tobacco-like and hay-like) (Fig. 1a). One major challenge in fundamental olfaction research, and which is also an important unresolved issue for perfumers, is to explain this complex perceptual processing on the basis of the structural features of the molecule. The present study hypothesized that an odorant which is structurally complex at the molecular level would also be described using multiple olfactory notes. To test this hypothesis, we examined the quantitative relationship between the structural complexity of odorants and the number of olfactory notes they evoked for experts and non-experts. The results from both sets of subjects revealed that the more complex the odorant's structure, the more numerous the olfactory notes it evoked. In non-experts, moreover, it was found that odorants of low structural complexity, evoking few olfactory notes, were also perceived as more unpleasant. Results Molecular complexity influences the number of olfactory notes. The relationship between the structural complexity of 411 odorants and the number of olfactory notes they evoked was examined. Odorant molecules were selected from the standardized Arctander atlas 2 , which contains descriptions by experts referring to various chemosensory qualities: olfactory and trigeminal notes as well as flavors. Firstly, to obtain a homogeneous measure of the number of olfactory notes across all odorants, a reference list was compiled, using a template developed by Chastrette and colleagues 3 which depicts the most relevant olfactory notes included in Arctander's book (see Methods). Secondly, the structural complexity of odorant molecules was measured, using a molecular complexity index initially developed by chemists to predict the probability of interaction between ligands (i.e., drugs) and receptors 4. This index, which takes into account both the elements SUBJECT AREAS: SENSORY SYSTEMS RECEPTORS BEHAVIOUR PLASTICIT