Predictive QSPR modelling for the olfactory threshold of a series of pyrazine derivatives

Abstract

Nowadays, much interest is shown in the prediction of different organoleptic properties of molecules for their prominent use in a variety of formulations and food products. Against this background, cheminformatics modelling was done in the present work for the development of predictive models for the olfactory threshold (log T) of a series of 74 pyrazine derivatives employing in silico techniques such as genetic function algorithm (GFA) and genetic partial least squares algorithm (G/PLS). Different categories of descriptors were calculated for the work. After validating the models both internally and externally, a parabolic GFA‐spline model was selected as the best model which showed significant predictive quality [Rpred2 = 0.822, = 0.641, = 0.019]. Interpretation of the descriptors concluded that increased hydrophobic surface area, along with an increase in the positive charge weighted solvent accessible surface area (as interpreted from the Jurs_DPSA_2 descriptor) in the molecules, provides a low value of log T. Again, the presence of an isopropyl group and electron richness of the molecules significantly influences the property profile (log T) of the molecules. Finally, 27 pyrazine derivatives were designed based on the present analysis and good in silico prediction values for odour threshold, i.e. low log T values were obtained from the developed model. Thus, use of this optimized quantitative structure–property relationship (QSPR) model may be used to screen molecule databases as well as modify the structures for selection of potent entities. Copyright © 2013 John Wiley & Sons, Ltd.

A sensory characterization of some N‐heterocycles in model spirit matrix: Influence of ethanol and several chemical features on aroma perception

“…Moreover, within the pyrazine series, both odour detection and recognition threshold values decreased with increasing number of alkyl substituents attached on the ring (2Ace3MePyz<2Ace3,5diMePyz<2,5diMePyz<5Et2,3diMePyz). This was consistent with other results revealing a strong influence of the degree of substitution on the pyrazine nucleus 48 and suggesting by quantitative structure–activity relationship (QSAR) a conformational and steric effect on the interaction with active sites of olfactory receptors 49–51 . Interestingly, the current findings also revealed that the presence of an acetyl functional group at 2‐position led to a significant decrease of both detection and recognition thresholds ( P ‐value <.05), whatever the nature of the heteroaromatic ring.…”

“…This was consistent with other results revealing a strong influence of the degree of substitution on the pyrazine nucleus 48 and suggesting by quantitative structure-activity relationship (QSAR) a conformational and steric effect on the interaction with active sites of olfactory receptors. [49][50][51] Interestingly, the current findings also revealed that the presence of an acetyl functional group at 2-position led to a significant decrease of both detection and recognition thresholds (P-value <.05), whatever the nature of the heteroaromatic ring. A number of N-heterocycles with acetyl function at position 2 have already been identified to present low odour thresholds.…”

Retronasal sensory characterization of aroma compounds in Baijiu by detection threshold measurement, retronasal OAVs, and time‐intensity evaluation

“…Among the four pyrazines studied, RDTs were continuously decreased with the increasing number of alkyl substituents attached to the ring, which was consistent with the result that both odor detection and recognition threshold values decreased in a spirit model medium (Goullet et al., 2023). Quantitative structure–activity relationship models of pyrazine‐based aroma compounds suggested a conformational and steric effect on the interaction with active sites of olfactory receptors (Buchbauer et al., 2000; Pal et al., 2013). Specifically, RDT of 2‐methylpyrazine was 63878.88 µg/L, about 0.52 times that of ODT, and RDT of 2,3,5,6‐tetramethylpyrazine was 1852.80 µg/L, with a one‐order magnitude difference between them.…”

Chemometric modeling of odor threshold property of diverse aroma components of wine

“…However, these studies did not consider modeling OTP of wine components. Again, although there are some reports of QSPR modelling of OTP of some classes of odorants in general (for example, pyrazine derivatives, 15 aliphatic alcohols, 16 diverse air-borne volatile organic compounds 17 ), there has been no attempt so far to model specifically the odorant components of wine. Such attempt will definitely help to understand the dependence of the odor quality of different types of wines on their aroma constituents (for example, different manufacturing conditions may lead to different composition of odorant constituents in wine leading to a difference in odor quality).…”