A method for the calculation of odor character from molecular structure.

The relationship between molecular structure and odor character is one of the most complex structure-activity problems in biology. Despite over a century of effort, it remains unsolved, and synthesis of new odorants still proceeds largely by trial and error. In previous work, I have argued that the reason for this failure lies in a mistaken assumption, namely that molecular shape determines odor character. Instead, I have taken up and extended an old idea (Dyson, 1938) according to which vertebrate olfactory receptors detect odorants by their molecular vibrations. I propose that the detection mechanism is inelastic electron tunnelling. If this is correct, there should be a correlation between the tunnelling vibrational spectra of odorants and their odor character. Here, using semi-empirical quantum chemistry methods and a simple calculation method for tunnelling mode intensities, I calculate the spectra of structurally diverse odorants belonging to various odor categories. With few exceptions, the calculated spectra of bitter almonds, musks, ambers, woods, sandalwoods and violets strongly correlate with odor character.

[1]  L. Ruzicka,et al.  Vielgliedrige heterocyclische Verbindungen III. Gewinnung des Hexamethylen‐imins und des Hexadecamethylenimins aus den aliphatischen Bromaminen , 1934 .

[2]  G. M. Dyson.  The scientific basis of odour , 1938 .

[3]  R. Moncrieff.  The chemistry of perfumery materials , 1949 .

[4]  R. H. Wright.  Odor and molecular vibration: neural coding of olfactory information. , 1977, Journal of theoretical biology.

[5]  M. Taylor,et al.  A quantitative analysis of the inelastic electron tunnelling spectrum of the formate ion , 1986 .

[6]  M. Veith,et al.  Sila-Riechstoffe und Riechstoffisostere XII . Geruchsvergleiche homologer Organoelementverbindungen der vierten Hauptgruppe (C, Si, Ge, Sn) , 1993 .

[7]  D. Zakarya,et al.  Structure–odour relations for bitter almond odorants , 1993 .

[8]  Relation between the Odor of (R)‐Ethyl Citronellyl Oxalate and its Stable Conformations , 1994 .

[9]  G. Ohloff,et al.  Scent and Fragrances: The Fascination of Odors and their Chemical Perspectives , 1994 .

[10]  G M Shepherd,et al.  Emerging principles of molecular signal processing by mitral/tufted cells in the olfactory bulb. , 1994, Seminars in cell biology.

[11]  L. Turin,et al.  A spectroscopic mechanism for primary olfactory reception. , 1996, Chemical senses.

[12]  Karen J. Rossiter,et al.  Structure−Odor Relationships , 1996 .

[13]  Charles S. Sell,et al.  The chemistry of fragrances , 1999 .

[14]  A. Williams.  THE SYNTHESIS OF MACROCYCLIC MUSKS , 1999 .

[15]  L. Buck,et al.  Combinatorial Receptor Codes for Odors , 1999, Cell.

[16]  P. Kraft,et al.  Synthesis of a Constitutional Isomer of Nerol by Consecutive Ireland–Claisen and Cope Rearrangements , 1999 .

[17]  P. Kraft.  Design and Synthesis of Violet Odorants with Bicyclo[6.4.0]dodecene and Bicyclo[5.4.0]undecene Skeletons , 1999 .

[18]  Philip Kraft,et al.  Odds and Trends: Recent Developments in the Chemistry of Odorants , 2000 .

[19]  Warren J. Hehre,et al.  A Guide to Molecular Mechanics and Quantum Chemical Calculations , 2003 .