Therapeutic discrepancy of diallyl trisulfide and diallyl disulfide in part may be attributed to the resonance-stabilization of allylic cations and trisulfide anions

Abstract

Accumulating pharmacological evidence has revealed that diallyl trisulfide (DATS) is uniquely active and its therapeutic effect prevails over diallyl disulfide (DADS). The cited reasons involve the bond dissociation energy, interconversion, lipophilicity, and polarizability of DATS. We hypothesize that the resonance-stabilized DATS could provide some unique chemical species, which are not likely to form from DADS. GC/MS analysis showed the formation of nine ionic species in DATS, and seven ionic species in DADS. The two ions uniquely formed from DATS are allyl trisulfide (ATS) and trisulfide (TS) anions. The high resonance energy of allylic cation, 37 kcal mol−1, facilitates the formation of allylic cation and TS anion from DATS. Consequently, the anions ATS and TS uniquely produced by DATS are likely critically important in the molecular bioactivity of DATS and probably function by enhancing the thiolation of glutathione and proteins producing microfilament oxidation and microtubule dysfunction.