Allicin, the principal organosulfur compound in garlic, has long been associated with a wide range of biological activities. However, emerging evidence suggests that these effects may arise not from allicin itself, but from sulfur compounds formed along its transformation pathways. To support this question computationally, we considered allicin together with a set of related sulfur compounds spanning its chemical transformation landscape, while accounting for the conformational space of each system, resulting in approximately 1100 structures overall. Because antioxidant activity is closely related to bond dissociation enthalpy (BDE), identifying a reliable model chemistry is a necessary first step. This is particularly challenging for sulfur-containing systems, as sulfur is highly polarizable, adopts multiple oxidation states, and participates in chemically distinct bonds such as S–S, S–O, C–S, S–H, C–H, and C–S=O. To address this complexity, a bond-type-specific benchmarking strategy was applied using a reference library of 77 representative organosulfur compounds [1]. Ten candidate model chemistries were assessed. Previous studies on sulfur-rich systems have identified hybrid functionals such as M06-2X and ωB97X-D as suitable for mechanistic thermochemistry and bond dissociation analysis [2,3]. Calculated and experimental BDEs were compared using mean absolute deviation, standard deviation, slope, intercept, skewness, and correlation coefficient. The mean absolute deviations remain largely within 4–7 kcal mol⁻¹ across the tested model chemistries, indicating overall agreement with experimental sulfur-centered bond energetics. Among the tested methods, ωB97X-D/6-311G(2d,p) provided the best balance of accuracy, error symmetry, and computational efficiency, offering a practical framework for subsequent mechanistic and thermochemical evaluation of allicin and allicin-derived sulfur compounds.

References

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