Ascorbic acid autoxidation

Autoxidation reactions of L-ascorbic acid (H2A) have been the subject of intensive studies for decades. It was shown that some of the most... 

The kinetic results reported by Jameson and Blackburn (11,12) for the copper catalyzed autoxidation of ascorbic acid are substantially different from those of Taqui Khan and Martell (6). The former could not reproduce the spontaneous oxidation in the absence of added catalysts when they used extremely pure reagents. These results imply that ascorbic acid is inert toward oxidation by dioxygen and earlier reports on spontaneous oxidation are artifacts due to catalytic impurities. In support of these considerations, it is worthwhile noting that trace amounts of transition metal ions, in particular Cu(II), may cause irreproducibilities in experimental work with ascorbic acid (13). While this problem can be eliminated by masking the metal ion(s), the masking agent needs to be selected carefully since it could become involved in side reactions in a given system. 

Reports by Li and Zuberbuhler were in support of the formation of Cu(I) as an intermediate (16). It was confirmed that Cu(I) and Cu(II) show the same catalytic activity and the reaction is first-order in [Cu(I) or (II)] and [02] in the presence of 0.6-1.5M acetonitrile and above pH 2.2. The oxygen consumption deviated from the strictly first-order pattern at lower pH and the corresponding kinetic traces were excluded from the evaluation of the data. The rate law was found to be identical with the one obtained for the autoxidation of Cu(I) in the absence of Cu(II) under similar conditions (17). Thus, the proposed kinetic model is centered around the reduction of Cu(II) by ascorbic acid and reoxidation of Cu(I) to Cu(II) by dioxygen ... 

Iron(III)-catalyzed autoxidation of ascorbic acid has received considerably less attention than the comparable reactions with copper species. Anaerobic studies confirmed that Fe(III) can easily oxidize ascorbic acid to dehydroascorbic acid. Xu and Jordan reported two-stage kinetics for this system in the presence of an excess of the metal ion, and suggested the fast formation of iron(III) ascorbate complexes which undergo reversible electron transfer steps (21). However, Bansch and coworkers did not find spectral evidence for the formation of ascorbate complexes in excess ascorbic acid (22). On the basis of a combined pH, temperature and pressure dependence study these authors confirmed that the oxidation by Fe(H20)g+ proceeds via an outer-sphere mechanism, while the reaction with Fe(H20)50H2+ is substitution-controlled and follows an inner-sphere electron transfer path. To some extent, these results may contradict with the model proposed by Taqui Khan and Martell (6), because the oxidation by the metal ion may take place before the ternary oxygen complex is actually formed in Eq. (17). 

In alkaline solution (pH 11), the complex is present as a p-oxo dimer and ascorbic acid is fully deprotonated. In the absence of oxygen, kinetic traces show the reduction of Fe(III) to Fe(II) with a reaction time on the order of an hour at [H2A] =5xlO-3M. The product [Fen(TPPS)] is very sensitive to oxidation and is quickly transformed to Fe(III) when 02 is added. This leads to a specific induction period in the kinetic traces which increases with increasing [02]. The net result of the induction period is the catalytic two-electron autoxidation of ascorbic acid in accordance with the following kinetic model (23) ... 

The kinetic consequence of the non-participating ligand was also noticed in the autoxidation reactions catalyzed by Ru(III) ion, Ru(EDTA) (1 1) and Ru(IMDA) (1 1) (EDTA = ethylenediaminetetraace-tate, IMDA = iminodiacetate) (24,25). Each reaction was found to be first order in ascorbic acid and the catalysts and, owing to the protolytic equilibrium between HA /H2A, an inverse concentration dependence was confirmed for [H+]. Only the oxygen dependencies were different as the Ru(III)-catalyzed reaction was half-order in [02], whereas the rates of the Ru(III)-chelate-catalyzed reactions were independent of [02]. In the latter cases, the rate constants were in good agreement with those... 

The presence of ascorbic acid as a co-substrate enhanced the rate of the Ru(EDTA)-catalyzed autoxidation in the order cyclohexane < cyclohexanol < cyclohexene (148). The reactions were always first-order in [H2A]. It was concluded that these reactions occur via a Ru(EDTA)(H2A)(S)(02) adduct, in which ascorbic acid promotes the cleavage of the 02 unit and, as a consequence, O-transfer to the substrate. While the model seems to be consistent with the experimental observations, it leaves open some very intriguing questions. According to earlier results from the same laboratory (24,25), the Ru(EDTA) catalyzed autoxidation of ascorbic acid occurs at a comparable or even a faster rate than the reactions listed in Table III. It follows, that the interference from this side reaction should not be neglected in the detailed kinetic model, in particular because ascorbic acid may be completely consumed before the oxidation of the other substrate takes place. 

The main features of the copper catalyzed autoxidation of ascorbic acid were summarized in detail in Section III. Recently, Strizhak and coworkers demonstrated that in a continuously stirred tank reactor (CSTR) as well as in a batch reactor, the reaction shows various non-linear phenomena, such as bi-stability, oscillations and stochastic resonance (161). The results from the batch experiments can be suitably illustrated with a two-dimensional parameter diagram shown in Pig. 5. 

In Fig. 6, separate regions of bi-stability, oscillations and single stable steady-states can be noticed. This cross-shaped phase diagram is common for many non-linear chemical systems containing autocatalytic steps, and this was used as an argument to suggest that the Cu(II) ion catalyzed autoxidation of the ascorbic acid is also autocatalytic. The... 

Slight SH, Prabhakaram M, Shin DB, Feather MS and Ortwerth BJ (1992) The extent of N-(carboxymethyl)lysine formation in lens proteins and polylysine by the autoxidation products of ascorbic acid. Biochim Biophys Acta 1117, 199-206. 

Autoxidation can lead to deterioration of food, drugs, cosmetics, or polymers, and inhibition of this reaction is therefore an important technical issue. The most important classes of autoxidation inhibitors are radical scavengers (phenols, sterically demanding amines [65, 66]), oxygen scavengers (e.g. ascorbic acid), UV-light absorbers, and chelators such as EDTA (to stabilize high oxidation states of metals and thereby suppress the metal-catalyzed conversion of peroxides to alkoxyl radicals) [67]. 

Systematic examination of the catalytic properties of dimeric complexes was initiated shortly after the identification of dinuclear iron sites in metalloenzymes. The first report of a reactive dimeric system came from Tabushi et al. in 1980, who examined the catalytic chemistry of [Fe3+(salen)]20, 1 (salen is N,N -(salicylaldehydo)-l,2-ethylenediamine) (12). They reported interesting stereoselectivity in the oxidation of unsaturated hydrocarbons with molecular oxygen in the presence of mercaptoethanol or ascorbic acid and pyridine as a solvent ([l]<<[alkane]<<[2-mercaptoethanol]). With adamantane as substrate, they observed the formation of a mixture of (1- and 2-) adamantols and adamantanone (Table I) (12). Both the relative reactivity between tertiary and secondary carbons (maximum value is 1.05) and final yield ( 12 turnovers per 12 hr) were dependent on the quantity of added 2-mercaptoethanol. Because autoxidation of adamantane gave a ratio of 3°/2° carbon oxidation of 0.18-0.42, the authors proposed two coexisting processes autooxidation and alkane activation. 

When, under identical conditions, ascorbic acid was used instead of mercaptoethanol, the reaction gave products with 3°/2° carbon reactivity of 0.28-0.42, suggestive of an autoxidation process (12). Furthermore, the kinetics of the reaction are biphasic for 2-mercaptoethanol and monophasic for ascorbic acid. These kinetics are consistent with the generation of a new catalytic system by the coordination of the thiol to the ferric center(s). For either reductant, bleaching of the complex was observed within minutes in the absence of substrate. 

M19. Miyata, T., Inagi, R., Asahi, K., Yamada, Y., Horie, K., etal., Generation of protein carbonyls by glycoxidation and lipoxidation reactions with autoxidation products of ascorbic acid and polyunsaturated fatty acids. FEBS Lett. 437, 24-28 (1998). 

Edetic acid and edetates are primarily used as antioxidant synergists, sequestering trace amounts of metal ions, particularly copper, iron, and manganese, that might otherwise catalyze autoxidation reactions. Edetic acid and edetates may be used alone or in combination with true antioxidants the usual concentration employed being in the range 0.005-0.1% w/v. Edetates have been used to stabilize ascorbic acid ... 

Catalysis of the Autoxidation of Ascorbic Acid by Metal Ions and Metal Chelates... 

Metal-Ion-Catalyzed Autoxidation. Figure 1 illustrates the variation of the first-order rate constants for the autoxidation of ascorbic acid by molecular oxygen with the concentration of the Cu (II) ion, which is present in catalytic (i.e. low) concentrations (8). The linear relationship indicates second-order behavior [first order in ascorbic acid and first order in Cu(II)]. The catalytic effect of Cu(II) is also seen to decrease... 

A reaction mechanism for the metal-ion-catalyzed autoxidation of ascorbic acid, involving the formation of an intermediate ternary ascorbate-metal ion-dioxygen complex, is illustrated in Scheme 2. Although the bonding between the metal ion and the dioxygen in the intermediate... 

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