Quantum Calculation for Musk Molecules Infrared Spectra towards the Understanding of Odor

It is not clear so far how humans can recognize odor. One of the theories regarding structure-odor relationship is vibrational theory, which claims that odors can be recognized by their modes of vibration. In this sense, this paper brings a novel comparison made between musky and nonmusky molecules, as to check the existence of correlation between their modes on the infrared spectra and odor. For this purpose, sixteen musky odorants were chosen, as well as seven other molecules that are structurally similar to them, but with no musk odor. All of them were submitted to solid theoretical methodology (using molecular mechanics/molecular dynamics and Neglect of Diatomic Differential Overlap Austin Model 1 methods to optimize geometries) as to achieve density functional theory spectra information, with both Gradient Corrected Functional Perdew-Wang generalized-gradient approximation (GGA/PW91) and hybrid Becke, three-parameter, Lee-Yang-Parr (B3LYP) functional. For a proper analysis over spectral data, a mathematical method was designed, generating weighted averages for theoretical frequencies and computing deviations from these averages. It was then devised that musky odorants satisfied demands of the vibrational theory, while nonmusk compounds belonging either to nitro group or to acyclic group failed to fulfill the same criteria. 1. Introduction 1.1. Theories regarding Odor Prediction and Recognition Musks are responsible for bringing sensuality and warmth to a fragrance [1], as well as adding their excellent fixative properties [2, 3]. Presently, natural products extraction involves high costs and generates small amounts of raw material, so synthetic odorants are greatly demanded. To properly design a new odorant, previous information on how odors are read is necessary. There are major recent advances on neurobiology, biophysics, biochemical fields [4–7], though it is still unclear how humans recognize odor. At this scenario, quantitative structure-activity relationship models (QSAR models) are valuable for the proposal of new potential musky smelling molecules [8–12]. Such approach allows for the reduction in the number of costly and unnecessary chemical syntheses. Theories regarding odor recognition at the biological level have also been discussed in the literature. One of them, known as the odotope theory [13–15], states that noncovalent bonds (i.e., weak repulsive and attractive interactions) between the molecule and the olfactory receptor (OR) proteins (responsible for decoding the molecule and starting transduction) would elicit a unique response