A Method for the Calculation of Odor Character from Molecular Structure

doi:10.1006/jtbi.2001.2504

Journal of Theoretical Biology

Volume 216, Issue 3, 7 June 2002, Pages 367-385

https://doi.org/10.1006/jtbi.2001.2504 Get rights and content

Abstract

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.

References (29)

G. FRATER et al.
Fragrance chemistry
Tetrahedron
(1998)
B. MALNIC et al.
Combinatorial receptor codes for odors
Cell
(1999)
K. MORI et al.
Emerging principles of molecular signal processing by mitral/tufted cells in the olfactory bulb
Semin. Cell Biol.
(1994)
U. WANNAGAT et al.
Sila-Riechstoffe und Riechstofffisostere XII. Geruchsvergleiche homologer organoelementverbindungen der vierten hauptgruppe (C, Si, Ge, Sn)
J. Organometallic Chem.
(1993)
R.H. WRIGHT
Odor and molecular vibration: neural coding of olfactory information
J. theor. Biol.
(1977)
S. ARCTANDER
Perfume and Flavor Chemicals
(1994)
A. BERGER-SCHUNN
Practical Color Measurement
(1994)
H. BOELENS
Relationship between the chemical structure of compounds and their olfactive properties
Cosmetics and Perfumery
(1974)
H. BOELENS et al.
Chemische Konstitution und Geruch
Chem. Zeitung
(1973)
BRUNKE, E. J. 1981,...

G.M. DYSON

The scientific basis of odour

Chem. Ind.

(1938)

W.J. HEHRE et al.

A brief guide to molecular mechanics and quantum chemical calculations

(1998)

P. KRAFT

Design and synthesis of violet odorants with bicyclo [6.4.0] dodecene and bicyclo [5.4.0] undecene skeletons

Synthesis

(1999)

KRAFT, P. EICHENBERGER, W. FRÁTER, G. 1999, Synthesis of a constitutional isomer of nerol by consecutive...

Cited by (75)

Bis-aldehydes: Versatile precursors for bis-heterocycles
2023, Advances in Heterocyclic Chemistry
Citation Excerpt :
Aldehydes serve as the equivalent of the alkyl carbocation in the electrophilic carbon atom of the C-O bond, which is typically subject to direct attack by nucleophiles.49 Tremendous synthetic flexibility makes aromatic aldehyde derivatives—among other aldehydes—good intermediates in the production of high-value materials like medicines and agrochemicals, as well as important end products in the fragrance and food industries.50–55 These aldehydes are mostly accessible through Friedel-Crafts functionalization of benzaldehyde derivatives or carbonylation of electron-rich arenes (such as the Vilsmeier-Haack reaction).56,57
The widest variety of organic molecules, with major uses in industry, biomedicine, and chemistry, are heterocycles. They can be found as scaffolds in several medications and other pharmaceutically active chemicals, dyes as well as in a variety of natural product. The high interest in heterocycles in the pharmaceutical and agrochemical industries is frequently linked to their natural occurrence. Additionally, the synthesis of bis-heterocycles has received a lot of attention in recent years because it was discovered that combining several heterocyclic cores into a single molecular system could take advantage of the pharmacological and altered physical characteristics of the resulting multivalent ligands. In particular, the methods used in the last ten years to synthesize bis-heterocycles utilizing bis-aldehydes as precursors are covered in this review. According to the kind of heterocyclic systems, the heterocyclic systems mentioned in this review are divided into categories. Except where an overall yield is given, yields of the target molecules reported in the review are given in the reaction's last step. The yields are not provided in the original articles in a few cases.
Rotational spectrum of Isochroman
2022, Journal of Molecular Structure
Citation Excerpt :
As one kind of benzopyrones, coumarin has a planar structure due to the π electron localization as revealed by rotational spectroscopic study [21]. Isochroman (3,4-dihydro-1H-2-benzopyran, C9H10O), with a unique smell of musk [2], can be considered as the pyrone moiety in coumarin replaced by a saturated six-membered oxygen heterocycle. Due to the bending and twisting motions of the saturated ring, two plausible conformers can be present for isochroman.
The ground state rotational spectrum of isochroman (3,4-dihydro-1H-2-benzopyran, C₉H₁₀O) has been studied by using a pulsed jet Fourier transform microwave spectrometer in the range of 5-20 GHz, complemented with theoretical calculations. Accurate spectroscopic parameters including rotational and centrifugal distortion constants were determined for the parent species and all mono-substituted ¹³C isotopologues in natural abundance, which allow the determination of the accurate geometry of the carbon skeleton. The semi-experimental structure was evaluated by taking into account the vibrational corrections calculated from the B3LYP-D3(BJ)/6-311++G(d,p) anharmonic force field. The electrostatic potential surface above the benzene ring with different saturated cycles (n = 3-7) has been calculated at the MP2/6-311++G(d,p) level, implying that the electron withdrawing effect of electronegative O and N atoms can be transferred from the adjacent saturated ring to the benzene ring.
The complexities of ligand/receptor interactions: Exploring the role of molecular vibrations and quantum tunnelling
2024, BioEssays
A Rapid Approach Based on Empirical Formulas and Graph Traversal Algorithms to Automatic Generation of Fragrance Formulas
2023, SSRN
A Desaturative Approach for Aromatic Aldehyde Synthesis via Synergistic Enamine, Photoredox and Cobalt Triple Catalysis
2022, Angewandte Chemie - International Edition
Medicinal Chemistry of Isocyanides
2021, Chemical Reviews

View all citing articles on Scopus

¹: E-mail: [email protected]

View full text

Regular ArticleA Method for the Calculation of Odor Character from Molecular Structure

Abstract

Tetrahedron

Cell

Semin. Cell Biol.

J. Organometallic Chem.

J. theor. Biol.

Perfume and Flavor Chemicals

Practical Color Measurement

Relationship between the chemical structure of compounds and their olfactive properties

Cosmetics and Perfumery

Chemische Konstitution und Geruch

Chem. Zeitung

The scientific basis of odour

Chem. Ind.

A brief guide to molecular mechanics and quantum chemical calculations

Design and synthesis of violet odorants with bicyclo [6.4.0] dodecene and bicyclo [5.4.0] undecene skeletons

Synthesis

Regular Article
A Method for the Calculation of Odor Character from Molecular Structure