Odor structure correlation

Odor/Structure Correlation attempts to elucidate the mechanisms which mediate the information transfer from structural featxires of a molecule to a corresponding information pattern. The latter originates in olfactory neurons and is encoded in nerve impulses. It is projected for further analysis, discrimination and recognition to the higher olfactory centers of the CNS. This information transfer includes the transduction process which converts chemical to electrical signals. 

In this communication the focus is on b) Odor/Structure Correlation. 

Therefore in any attempt of odor-structure correlation not the total (or overall) structure of the molecule should be considered but the individual contributions of the molecular profiles. Perhaps this could be done by a combination of computer assisted conformational analysis of the odorivectors which would provide information about the nature of the explicit and implicit profiles as well as the probability of the formation of the latter, with multidimensional scaling of the highly processed information the odorivectors deliver. 

In the pheromone orientation system it has been shown how important time aspects are. Several species will not be attracted to a pheromone source unless the stimulus arrives in a pulsed fashion, mimicking the filamentous structure of a natural odor plume. Correlates to this requisite have been found among AL neurons, where both fast neurons, able to code fast fluctuations in concentration, and slow neurons, seemingly only coding qualitative aspects of the plume, are present. 

Reviews of the association of chemical and sensory aspects were published as early as 1965 by Wick and later, for instance, by Vernin (1981), who gave examples of odor-structure relationship. Different structures can be related to similar odors, similar structures to different odors, and similar structures to similar odors. A statistical treatment of data became necessary to correlate analytical results with those obtained by sensory analysis, as stated by Adda and Jounela-Eriksson (1979). Since then, correlation between sensory analysis and instrumental analysis has been the subject of important sessions of the Weurman Flavor Research Symposia, for instance in the chapters on Sensory science in flavor research (Weurman 5th Meeting, 1987) or Correlation between sensory and instrumental analysis (Weurman 7th meeting, 1993). 

One aim of studying olfaction has been to gain an understanding of how the physical features of odor molecules correlate with their perceptual qualities. Unfortunately, the perceptual qualities do not often follow an easily ordered metric that can be simply related to molecular structures. We might, therefore, speak of a dual problem in attempting to relate odor perception to the features of the corresponding molecules no obvious metric is available to describe either the space of odor perceptions or the space of odor chemistry. 

Some studies have examined the ability of animals to discriminate among odor stimuli and have attempted to correlate failures of discrimination with structural similarity among odor molecules. These studies may be used to form indices of the perceptual similarity of odors, and this may provide information about the way that a limited variety of chemical structures (e.g., alcohol groups or double-bonded oxygen moieties (ketones)) are used as features by the olfactory system Recent behavioral experiments using aliphatic alcohols, ketones, and aldehydes have shown that the perceptual qualities of odors are correlated with molecular features such as... 

Consider that the odor perception by human nose is correlated with the odor value, OVj, in the headspace above the liquid. If a specific OVt distribution values is wanted, the perfume composition can be determined with the help of Equation (2). This methodology can facilitate the optimization of perfume compositions, reducing in this way some trial and error time and chemical wastes. Clearly, the problem is determined by structural decisions because the perfume composition depends on the interaction of the different perfume components. 

Odor and taste quality can be mapped by multidimensional scaling (MDS) techniques. Physicochemical parameters can be related to these maps by a variety of mathematical methods including multiple regression, canonical correlation, and partial least squares. These approaches to studying QSAR (quantitative structure-activity relationships) in the chemical senses, along with procedures developed by the pharmaceutical industry, may ultimately be useful in designing flavor compounds by computer. 

ODOR. An important property of many substances, manifested by a physiological sensation caused by contact of their molecules with the olfactory nervous system. Odor and flavor are closely related, and both are profoundly affected by submicrogram amounts of volatile compounds. Attempts to correlate odor with chemical structure have produced no definitive results, Objective measurement techniques involving chromatography are under development. Even potent odors must be present in a concentration of 1,7 x I07 molecules/cc to be detected. It has been authentically stated that the nose is 100 times as sensitive in detection of threshold odor values as the best analytical apparatus. 

It should be stressed that for many compounds the yields were too low for identification experiments. It is, therefore, a prerequisite in the application of the AEDA on headspace extracts that the key odorants have already been identified in preliminary experiments and can be used as reference compounds to correlate the odor-active regions with the chemical structures on the basis of retention indices. 

The influence of structural features of benzodioxepine and benzodithiepine derivatives on rat brain benzodiazepine receptors has been studied <1996MSR589>. A group at Givaudan has synthesized and studied the conception, characterization, and correlation of new marine odorants based on the benzo[A][l,4]dioxepinone system <2003EJO3735>. 1,4-Dithiapane was among a data set of 101 hetero sulfamate sodium salts that was tested as potential sweeteners in a structure-taste relationship study <2000J(P2)1369>. 

Odor, however, is a very obvious property of any chemical compound, and thus, speculation about the mechanism of perception is very tempting. Experienced fragrance chemists can predict odor type with much better than random accuracy, and a commercial driver exists in terms of design of novel materials for the fragrance industry. Therefore, it is not surprising that many structure/odor correlations and olfaction models have been reported and debated, often very hotly, in the literature. 

Sell C. Structure/odor correlations, the mechanism of olfaction and the design of novel fragrance ingredients. Perfumer Flavorist 2000 25 67-73. 

Structure-activity relationships have been largely employed for molecular design these correlations depend on the molecular representation and the activity landscape. The molecular representation depends only on the small molecule, whereas the activity landscape provides information on the ligand-receptor complex, for example, how permissive the binding pocket is. To exemplify the molecular similarity approach, a set of odorants (compared to benzaldehyde) will be presented. 

Hansen A, Rolen SH, Anderson K, Morita Y, Caprio J, Finger TE (2003) Correlation between olfactory receptor cell type and function in the channel catfish. J Neurosci 23 9328-9339 Hansen A, Anderson KT, Finger TE (2004) Differential distribution of olfactory receptor neurons in goldfish structural and molecular correlates. J Comp Neurol 477 347-359 Hashiguchi Y, Nishida M (2006) Evolution and origin of vomeronasal-type odorant receptor gene repertoire in fishes. BMC Evol Biol 6 76... 

If the odors of specific objects translate into unitary percepts, which constitute the basic entities in linguistic descriptions of olfaction, then the question follows as to whether these unitary percepts take shape at the level of the receptor neurons or in the olfactory bulb or elsewhere in the brain. That question remains unanswered, as of this writing. Because the sense of smell does not correlate perfectly with externally monitored patterns of electrical response from the receptor neurons or the olfactory bulb, the nature of olfactory coding remains unknown. Outside the laboratory unitary percepts rarely equate to pure compounds. Two vocabularies coexist, one of smells (which varies from individual to individual, and which refers to other inputs besides olfaction) and the other of chemical structures. 

Another common failing in the logic behind odour theories is the inability to distinguish between cause and effect. All too often, someone finds a correlation between two parameters and assumes a causal relationship, without asking whether this correlation could simply be between two effects of a common cause. An example of this in the field of olfaction is the assumption that a correlation between the infrared spectra of a set of odorants and their odours demonstrates that the odour was caused by those specific vibrations. The odours and the spectra are both effects of a common cause, that is, the molecular structure. 

Structure-odour correlations rely on the measurement of odour. It must be remembered that odour is not a physical property. Odour exists in the mind. We must not assume that it exists in the receptor also. The fact that cross-adaptation can occur between chemically different materials with similar odours, and also between chemically similar materials with different odours, suggests that it does not. There is no evidence that the receptors are tuned to specific odours or even odour types. It is quite likely that the recognition process is based on physical and/or chemical properties of odorants and that odour only exists when the brain puts an interpretation onto a pattern of signals from the olfactory nerves. 

Equally, what we term odour is, in fact, the end result of a number of discrete processes. In consequence, we cannot assume that any correlation between agent and effect arises from only one of these. All too often it is assumed that only the interaction between the odorant and the receptor protein is of significance and that structure-odour correlations give mechanistic information about this specific event. 

ADAPT has been developed and used by Jurs in a wide range of SAR applications. In the field of olfaction these include the correlation of odour intensities for 58 structurally and organoleptically diverse odor-... 

In the field of odorants, we find examples of structurally different compounds with similar odour qualities and structurally similar compounds with different odour qualities. A notable example is the well-defined musk odour that can be found within five very different structural families (Figure 14.10). However, within each family there are very tight structural criteria. A very small structural change, such as the addition of one methyl group, can cause complete destruction of the musk odour. This creates a problem for the SAR worker. Some have searched for correlations within a family, while others have tried to speculate on molecular parameters common to all groups. 

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