Is It Possible to Predict the Odor of a Molecule on the Basis of its Structure?

How, by looking at the structure of a molecule, does Professor Marie-Laure Fauconnier predict its smell?

This is the subject of his latest scientific article entitled "Is It Possible to Predict the Odor of a Molecule on the Basis of its Structure?" published in the International Journal of Molecular Sciences.

Olfactory is the dominant sensory perception for many animals. When Richard Axel and Linda B. Buck were awarded the Nobel Prize in 2004 for the discovery of the role of G-protein coupled receptors in olfactory cells, they highlighted the importance of olfaction for the scientific community.

Several theories have tried to explain how the cells of the olfactory bulb are able to distinguish such a variety of odorous molecules: depending on the sources, from 400,000 to one million different molecules. And the answer to the question "Can we predict the smell of a molecule based on its structure?" is far from trivial.

For many classes of compounds, the odour of a volatile molecule can be predicted with reasonable accuracy by structural analogy. For example, esters have a fruity and floral odour, lactones have a coconut or apricot character, amines have an animal or roasted odour, thiols have a rotten or garlic odour, volatile fatty acids have a sour to rancid odour and aldehydes are associated with green odours such as fresh cut grass. 

On the other hand, molecules with similar structures will have very different odours. This is particularly striking for enantiomers, molecules that have exactly the same structure but are "mirror images" of each other and usually have a different smell. To complicate the picture even further, molecules with completely different structures will have the same smell.

In this article, the latest knowledge in the field of olfaction is described. As much as the functioning of sight and hearing are described in great detail in the scientific literature, this is still not the case for olfaction.

There are 396 olfactory receptors in humans, which can interact with a variable affinity with several different compounds, whereas the same molecule can be perceived by several distinct receptors. It is a neural processing of information that ultimately allows the association of an odour to a given molecule. In addition, gender, age, cultural background and individual differences contribute to the variations in odour perception that complicate the picture. 

Olfactory studies are no longer limited to perfumers and flavourists. The importance of the olfactory sense is increasingly attracting the attention of the medical field. A deficient olfactory system has an impact on physical health, nutrition and the pleasure of eating, and more generally, on the quality of life. Raising awareness of the importance of olfaction for human health is crucial. Loss of smell can be a precursor to neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease and can help in their diagnosis.

In many countries, sniffing food is considered rude. This cultural issue has gradually contributed to the decline of olfaction in daily life.

From a public health perspective, it is crucial to restore the central role of olfaction between our five senses by changing attitudes and encouraging children to feel and appreciate what they eat. Seniors should also stimulate their sense of smell to counteract their loss of olfactory capacity.

The large inter-individual variations in olfactory capacities and the increase in the data sets collected in olfactory studies open the way to new fields of study such as the development of highly advanced electronic noses through "machine learning". These advances should contribute to a better understanding of the structural relationship between a volatile molecule and olfactory perception.