Multidimensional conformational analysis of allyl methyl disulfide: a key component of garlic

Organosulfur compounds in garlic, like allyl methyl disulfide, have been found to be involved in antimutagenic, anticarcinogenic, antithrombotic, and lipid-lowering activities, and it has also been found to act as an antioxidant. Ab initio molecular computations were performed on dihydrogen disulfide (1) with respect to torsional angle tau(1) = tau(H . S-S . H), hydrogen methyl disulfide (2) with respect to torsional angle tau(1) = tau(H . S-S . CH3), and allyl methyl disulfide (3) with respect to torsional angles tau(1) = tau(H3C2. CH2. S-S . CH3), tau(2) = tau(H3C2. CH2-S . S . CH3), and tau(3) = tau(H3C2-CH2. S . S . CH3). Potential energy curves (PEC) were obtained from 1 and 2, i.e., E = E(tau(1)), from which optimized structures were obtained at the HF/6-31G* level of theory. These optimized structures were used to investigate the potential energy hypersurface surface (PEHS) of 3, i.e., E = E(tau(1),tau(2),tau(3)). One-dimensional scans along tau(2) and tau(3) (where tau(1) = +/- 90%; tau(1) = 180%) were performed at the HF/3-21G* level of theory. From these scans, six lower energy pairs of enantiomeric minima (i.e., [g(+)g(+)g(+) \ g(-)g(-)g(-)], [g(+)ag(-) \ g(-)ag(+)], [g(+)g(-)g(+) \ g(-)g(+)g(-)], [g(+)g(+)g(-) \ g(-)g(-)g(+)], [g(+)ag(-) \ g(-)ag(+)], and [g(+)g(-)g(-) \ g(-)g(+)g(+)]) as well as 3 higher energy minima (i.e., [g(+)g(+)s \ g(-)g(-)s], [g(+)as \ g(-)as], and [g+g(-)s \ g(-)g(+)s]) were optimized at tau(1) = +/- 90% at the HF/6-31G* and B3LYP/6-31G* levels of theory. The global minimum was determined to be the [g(+)g(-)g(+) \ g(-)g(+)g(-)] enantiomeric pair of conformers, and the fully symmetrical anti-anti-anti [a a a] structure was determined to be a second-order saddle point on the PEHS of 3. Although there are no stereocentres in 3, there is chirality in the conformational twist with respect to the [a a a] conformation through tau(1) = tau(2) = tau(3) = 180%. Based on the energies and MO diagrams of the HUMO and LUMO +1 of 3, the anticarcinogenic and cholesterol lowering activity mechanism of 3 is presented.