Garlic: source of the ultimate antioxidants--sulfenic acids.

ion of an allylic H atom. Clearly, allicin is not directly responsible for the inhibition of ML autoxidation; instead, an allicin decomposition product must be responsible. We also explored the effects of added hydrogen-bondacceptor (HBA) solvents on allicin-inhibited autoxidation reactions. Although the addition of CH3CN (1m) to a solution of allicin in chlorobenzene had little effect on the rate of decomposition of allicin (Figure 1b), it markedly reduced the ability of allicin to inhibit the autoxidation of ML (Figure 1a). Thus, the use of freshly purified (HPLC) allicin in chlorobenzene in the presence of CH3CN (1m) led to an almost eightfold increase in the rate of inhibited autoxidation, and the stoichiometric factor dropped from n= 0.95 to 0.69. Since allicin itself is not the radical-trapping antioxidant in these autoxidation reactions, we cannot derive an inhibition rate constant (kinh) from the autoxidation data in the customary way; however, the drop in antioxidant activity in HBA solvents is informative. This type of solvent effect is well documented for reactions of peroxyl radicals with H-atom donors that are HBDs, such as phenols. The decomposition product of allicin, 2-propenesulfenic acid, is expected to be a strong HBD that will form strong hydrogen bonds with CH3CN (Scheme 1) and thus lead to a decrease in the rate of the inhibited autoxidation, as observed. Although these experiments demonstrate that 2-propenesulfenic acid is highly likely to be the peroxyl-radical scavenger in allicin-inhibited autoxidation reactions, the reason that sulfenic acids appear to be such effective antioxidants is currently unclear. Since the O H bonddissociation enthalpy (BDE) of an H-atom donor, XOH (e.g., phenols, X=Ar), is the key thermodynamic parameter connected with the rate of reaction of XOH with peroxyl radicals, it would be desirable to compare the O H BDE of 2-propenesulfenic acid and other sulfenic acids with the O H BDEs of their isoelectronic cousins, the hydroperoxides (which react with peroxyl radicals much more slowly, with Figure 1. a) Thermally initiated (azobisisobutyronitrile (AIBN), 40 mm) autoxidation of methyl linoleate (91 mm) at 37 8C in chlorobenzene containing allicin (50 mm) and HFPA (0.15m, *), CH3CN (1m, &), or no additive (~). b) Decomposition of allicin (50 mm) at 37 8C in chlorobenzene containing HFPA (0.15m, *), CH3CN (1m, &), or no additive (~). Scheme 1. Mechanistic scheme to explain the observed increase in the rate of allicin-inhibited autoxidation in the presence of acetonitrile. Zuschriften 164 www.angewandte. de 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. 2009, 121, 163 –166 rate constants of approximately 10–10m 1 s ). Unfortunately, no sulfenic acid O HBDE has ever been reported. As the reliable determination of a sulfenic acid O H BDE appeared to be experimentally impractical (owing to the transient nature of most known sulfenic acids), we calculated these BDEs by using a method known to accurately predict O H BDEs, the complete-basis-set approach of Petersson and co-workers (Table 1). Table 1 reveals two important features of the O H BDEs of sulfenic acids. First, the values are much lower than those for the analogous hydroperoxides. For the simplest members of the series (hydrosulfenic acid and hydrogen peroxide), the difference is 14.2 kcalmol . For the alkanesulfenic acids and alkyl hydroperoxides, the difference is even larger: almost 18 kcalmol 1 for methane-, 2-propene-, and a-toluenesulfenic acids and the corresponding hydroperoxides. Thus, the sulfur atom imposes two effects: It stabilizes the radical to a greater extent, largely by delocalizing the unpaired electron onto itself (the unpaired spin distribution is close to 50:50 between the oxygen and sulfur atoms in sulfinyl radicals and 70:30 between the terminal and nonterminal oxygen atoms in peroxyl radicals), and this results in greater interactions with substituents that are bonded to the sulfur atom. This effect leads to a greater difference between hydrosulfenic acid and the alkanesulfenic acids (ca. 4.5 kcalmol ) than between hydrogen peroxide and the alkyl hydroperoxides (ca. 1 kcal mol ). The O H BDEs of sulfenic acids are among the weakest known and comparable to those of hydroxylamines, such as TEMPO-H (70.7 kcalmol ; TEMPO= 2,2,6,6-tetramethylpiperidin-1-oxyl). 20] To provide additional insight into the reactions of sulfenic acids with peroxyl radicals, we also calculated the transitionstate (TS) structures (Figure 2) and associated activation energies of some representative reactions (Table 2). Two TS structures were identified: one with a cisoid geometry with respect to the oxygen atoms between which the H atom is being transferred (Figure 2a) and one with a transoid geometry (Figure 2b). The cisoid TSs were found to be lower in energy by approximately 6–7 kcalmol 1 than the transoid TSs (Table 2). The highest occupied molecular orbitals (HOMOs) of the cisoid and transoid TS structures (which comprise the four possible combinations of the two p* orbitals on the sulfinyl and peroxyl fragments between which the H atom is transferred) reveal why the cisoid geometry is favored. Whereas the singly occupied (SO) HOMO and HOMO-1 in the cisoid (Figure 2c) and transoid TS structures are very similar, HOMO-2 and HOMO-3 are quite different in the two TS geometries: There is significant bonding overlap between the sulfenic acid sulfur atom and the internal oxygen atom of the peroxyl radical in the cisoid structure, an interaction that is absent in the transoid structure. This bonding overlap suggests that the electron to be transferred from the sulfenic acid to the peroxyl radical is partly localized on the peroxyl radical in the cisoid TS and thus indicates a mechanism based on proton-coupled electron transfer (PCET). As in other PCETreactions, H-atom transfer between a sulfenic acid and a peroxyl radical is predicted to involve initial formation of a hydrogen-bonded complex, RSOH··· COOR’. For the reactions we investigated, in which R and R’ were alkyl groups, these complexes lie some 4.5 to 5.0 kcal mol 1 lower in energy than the separated reactants. This result implies that the corresponding TSs are slightly lower in energy than the separated reactants. These reactions are, therefore, predicted to be diffusion-controlled, consistent with Koelewijn and Berger s estimate that the rate constant for the reaction of 2-methyl-2-propanesulfenic acid with Table 1: O H BDEs (in kcalmol ) calculated by the CBS-QB3 method for some sulfenic acids and hydroperoxides.