Introduction
During the last decade a revival of studies about structure-odour
relationships can be noticed in the literature, such as the
publications of Rossiter (1996-1998), Pybus and Sell (1999-2001), and
of Turin and Yoshii (2001). It seems worthwhile to compare the
qualitative statements about structure-odour relationships of about
50 years ago with the more modern insights.
Discussion
In studies concerning structure-activity-relationships we assume that
the activity is due to a single molecule (monomolecular) and not to a
random group of an unknown number of molecules.
If the activity is monomolecular then the statement of Beets can be
useful. He stated in his theorem* in 1957: "When we draw the
structure of an unknown organic compound with all substituents in
their correct positions and with complete indications of
configurational details we have at the same time irrevocably and
fully defined all the properties, chemical, physical and
physiological, including the odour which the compound will have".
Also in 1957 Stoll wrote: "There is no doubt that there are as many
relationships of structure to odour as there are structures of odour
substances. When we attempt to classify a number of these facts in
order to arrive at some general conclusions, we run into many
exceptions. In truth one should treat only the relationships between
molecular structure and odour of a few well specified
substances".
About 10 years later Bedoukian (1966) mentioned, that "We are still
not able to relate molecular structure to odour. As a result of our
lack of knowledge in this area, it is not yet possible to predict the
odour of a substance with any degree of accuracy". In 1967 Hornstein
and Teranishi wrote: "There have been many attempts to correlate
chemical structure and odour quality, but the results have been
disappointing". One year later McCartney mentioned: "Although it
seems impossible that there should be no relationships between the
odour of chemical compounds and their constitutions it has to be
admitted that the difficulties in the way of uncovering the
connection are very great".
What is the situation of the art in structure-odour relationships
today? Rossiter wrote in 1996: "It is noticeable that whatever odour
"rules" are deduced, there are always exceptions. The non-odoriferous
exceptions are probably explained by steric hindrance to a receptor
fit or lack of volatility, but compounds which have anomalous odour
characteristics or intensities are not as easy to explain".
In 2001 Sell mentioned: "There are many examples of cases where two
very similar molecules elicit very different odour, yet a third
molecule which apparently bears little structural resemblance to
either of the first two, elicits an odour very similar to one of
them". Turin and Yoshii (2001) wrote: "Neither theory, when faced
with a novel molecule, is yet able to predict reliably what its odour
character will be" and "The fact that after several decades of
experimental investigations the basic mechanism by which odours are
detected remains open to question, shows that there is much work to
be done".
The structure of a chemical compound can be described by its complete shape (form, volume, profile) of stereochemical configuration and its electronic charge-distribution over the whole molecule, including e.g. dielectrical constant and dipole moment. The complete stereochemical configuration of a molecule can be called its "stereocity" and the complete electronic charge-distribution its "electronicity". In following publications it will be demonstrated that isosteric (resembling stereocity) and isoelectronic (resembling electronicity) molecules can reveal a certain resemblance in odour character. Some examples of isosteric compounds are isobutenyl- and phenyl groups and isoamyl and cyclohexyl derivatives and examples of isoelectronic compounds are aldehyde and nitrile groups and methyl esters and methyl ketones. All the isosteric and isoelectronic compounds are commercial aroma chemicals.
Concluding remarks
Old and new statements about qualitative structure-odour
relationships were compared. There has not been a lot of progress in
this field during the last 50 years. The structure of odourant
molecules can be described by its stereocity and its electronicity.
It will be demonstrated that several groups of isosteric and
isoelectronic compounds with more or less reminiscent odour qualities
are commercially available today.
(*Theorem is a statement susceptible of logical proof when certain facts are accepted as true according to the New Webster's Dictionary and Thesaurus of the English Language 1991)
Reprinted by Leffingwell & Associates, 2006, with Permission