Oxidation of sterols: Energetics of C–H and O–H bond cleavage

ion from the –CH2– groups in a-position to a C@C double bond (C7–H in D-sterols, C23–H in the two avenasterols and D-fucosterol, C6–H in D-sterols, or C23–H in D-gramisterol, D-episterol and D-citrostadienol). In the case of 2-propene, the experimentally determined BDE for CH2@CH–CH2–H bond (370 ± 2) kJ mol 1 was practically identical with the C6H5CH2–H BDE for toluene due to the conjugation in the subsequently formed benzyl and allyl radical (Ellison, Davico, Bierbaum, & DePuy, 1996). This experimental values are ca. 30 kJ mol 1 higher than the B3LYP/6-31G⁄ BDE values for hydrogen splitting-off from methyl groups in a-position to C@C double bonds, i.e. the C24–H BDE in the two avenasterols, and D-fucosterol. Although the used computational approach may slightly underestimate the BDE values, it describes the observed trends correctly (Klein & Lukeš, 2006; Klein et al., 2007; Rimarčík, Lukeš, Klein, & Rottmannová, 2011). On the other hand, one should keep in mind that the obtained gas-phase values are usually close, but not necessarily identical, with the experimental solution-phase BDEs, which are, in general, higher (Klein & Lukeš, 2006; Klein et al., 2007; Rimarčík et al., 2011). Significantly larger O–H BDEs (in comparison to C–H BDEs) are in accordance with the experimentally observed minor, slower oxidation including OH group at C3 carbon (Menéndez-Carreño et al., 2010; Smith, 1987, 1996). The results compiled in Table 1 also confirm that in the case of intensively studied D-sterols, the C7–H bond has the lowest C–H BDE for the molecules without the C@C double bond in the side chain (D-cholesterol,D-22-dihydrobrassicasterol,D-campesterol, D-sitosterol). In D-avenasterol and D-fucosterol C7–H BDE also remains the lowest one, although in their side chains, a double bond is present. These values are in agreement with the results of experimental studies of sterols oxidation, where it was found that the C7–H bond represents the major site of oxidation attack (Johnsson, Andersson, &Dutta, 2003; Johnsson&Dutta, 2003; Lampi et al., 2002;Menéndez-Carreñoet al., 2010;Oehrl et al., 2001; Smith, 1987, 1996). Easier hydrogen abstraction from the carbon atom in the a-position to the C@C double bond due to the low C–H BDE was confirmed also for D-sterols. In this group of sterols, C14–H BDE is the lowest one (see Table 2). In all studied D-sterols, we found C14–H BDEs almost identical – they reached values in a very narrow 312–314 kJ mol 1 range. Unfortunately, this result cannot be validated by an experiment, since we have not found any experimental work related to D-sterols oxidation and analysis of oxidation products. When we compare the lowest B3LYP/6311++G⁄⁄ C–H BDEs in D-sterol and D-sterol nuclei (Table 3), from the thermodynamics point of view, the C14–H bond in D-sterols should be even more vulnerable to oxidation attack in comparison to the C7–H bond in D-sterols. The bond dissociation enthalpies for the C4–H in D-sterols or C9–H and C6–H bonds in D-sterols, which are also in the a-position to the C@C double bonds, reached values higher by ca. 10–20 kJ mol 1 in comparison to the C7–H in D-sterols and C14–H bond in D-sterols. The BDEs compiled in Tables 1–3 indicate that the D-sterol nuclei may show lower oxidation stability than the D-sterols. In other words, the D-sterols can act as more effective antioxidants from the thermodynamics point of view because of lower enthalpies of homolytic C–H bond cleavage. From the oxidation kinetics point of view, lower BDEs should correlate with higher oxidation rates. 3.2. Bond dissociation enthalpies for Dand D-sterols side chains Experimental results (Gordon & Magos, 1983; Johnsson & Dutta, 2003; Johnsson et al., 2003; Lampi et al., 2002; Menéndez-Carreño Table 1 B3LYP/6-31G⁄ O–H and C–H bond dissociation enthalpies (BDE) of D-sterols. The lowest value in the molecule is set in bold.