Structure–Odor Correlations in Homologous Series of Alkanethiols and Attempts To Predict Odor Thresholds by 3D-QSAR Studies

Abstract

Homologous series of alkane-1-thiols, alkane-2-thiols, alkane-3-thiols, 2-methylalkane-1-thiols, 2-methylalkane-3-thiols, 2-methylalkane-2-thiols, and alkane-1,ω-dithiols were synthesized to study the influence of structural changes on odor qualities and odor thresholds. In particular, the odor thresholds were strongly influenced by steric effects: In all homologous series a minimum was observed for thiols with five to seven carbon atoms, whereas increasing the chain length led to an exponential increase in the odor threshold. Tertiary alkanethiols revealed clearly lower odor thresholds than found for primary or secondary thiols, whereas neither a second mercapto group in the molecule nor an additional methyl substitution lowered the threshold. To investigate the impact of the SH group, odor thresholds and odor qualities of thiols were compared to those of the corresponding alcohols and (methylthio)alkanes. Replacement of the SH group by an OH group as well as S-methylation of the thiols significantly increased the odor thresholds. By using comparative molecular field analysis, a 3D quantitative structure-activity relationship model was created, which was able to simulate the odor thresholds of alkanethiols in good agreement with the experimental results. NMR and mass spectrometric data for 46 sulfur-containing compounds are additionally supplied.

Copper-mediated thiol potentiation and mutagenesis-guided modeling suggest a highly conserved copper-binding motif in human OR2M3

“…Thiols are important carriers of information-as key food odorants, determining the aroma of foods [6,21], as body odors [18,19], or as environmental odors [20]. The observation that thiols, compared to other volatiles, frequently display particularly low odor thresholds [23][24][25]101], sprouted various theories trying to explain this behavior, with the aim to gain an understanding of odorant information coding at the receptor level. Common to all of these theories is the association of a thiol-receptor interaction with participation of transition metal ions such as copper, zinc, or nickel [27-31, 46, 47].…”

“…Thiols play an outstanding role in human olfaction, for instance as body odor [15][16][17][18][19], environmental odors [20], and especially as key food odorants (KFOs), which appear in foods at concentrations above their odor threshold, and critically determine the aroma of foods [21]. Thiol odorants often show very low odor thresholds [6,[21][22][23][24][25]. The olfactory sensitivity for thiols is shown not only for humans but also for spider monkeys (Ateles geoffroyi), squirrel monkeys (Saimiri sciureus), and pigtail macaque (Macaca nemestrina) [26].…”

The unusual influence of hetaryl groups on the direct conversion of some secondary alcohols into thiols with Lawesson’s reagent: elucidation of the reaction mechanism

“…toluene, the initially formed diphenylmethanethiol (4a) behaves differently and reacts with the monomer of Lawesson's reagent to give, after elimination of H 2 S, dibenzhydryl (4-methoxyphenyl)trithiophosphonate (5). However, in the presence of water 4a is the exclusive product.…”

“…Diverse methods are known for their preparation [1], and in recent years, asymmetric syntheses of thiols have been studied extensively [2,3]. It is well known that many thiols are biologically active substances [4] and some of them are of special interest as odorous compounds [5].…”

Odor threshold prediction by means of the Monte Carlo method

“…There are attempts to build up QSPR/QSAR for the odor threshold (Xu et al, 2012;Pal et al, 2014;Polster and Schieberle, 2015 ). The aim of present work was building up a predictive model for the odor threshold (mg/m 3 ) using the Monte Carlo method available via the CORAL software (CORAL, 2016).…”