Copper +-ascorbic acid reactions

In acidic solution, the degradation results in the formation of furfural, furfuryl alcohol, 2-furoic acid, 3-hydroxyfurfural, furoin, 2-methyl-3,8-dihydroxychroman, ethylglyoxal, and several condensation products (36). Many metals, especially copper, cataly2e the oxidation of L-ascorbic acid. Oxalic acid and copper form a chelate complex which prevents the ascorbic acid-copper-complex formation and therefore oxalic acid inhibits effectively the oxidation of L-ascorbic acid. L-Ascorbic acid can also be stabilized with metaphosphoric acid, amino acids, 8-hydroxyquinoline, glycols, sugars, and trichloracetic acid (38). Another catalytic reaction which accounts for loss of L-ascorbic acid occurs with enzymes, eg, L-ascorbic acid oxidase, a copper protein-containing enzyme. 

Many reactions catalyzed by the addition of simple metal ions involve chelation of the metal. The familiar autocatalysis of the oxidation of oxalate by permanganate results from the chelation of the oxalate and Mn (III) from the permanganate. Oxidation of ascorbic acid [50-81-7] C HgO, is catalyzed by copper (12). The stabilization of preparations containing ascorbic acid by the addition of a chelant appears to be negative catalysis of the oxidation but results from the sequestration of the copper. Many such inhibitions are the result of sequestration. Catalysis by chelation of metal ions with a reactant is usually accomphshed by polarization of the molecule, faciUtation of electron transfer by the metal, or orientation of reactants. 

Drugs can also Interfere with laboratory results by negating certain nonspecific oxidation and reduction reactions essential for the chemical assay. Penicillin, streptomycin and ascorbic acid are known to react with cupric Ion thus, false positive results for glucose may occur If a copper reduction method Is used. If the specific enzymatic glucose-oxidase method Is employed, ascorbic acid can cause a false negative result by preventing the oxidation of a specific chromogen In the reaction. 

The formation of the [M(HA)](" 1>+ complex was confirmed in independent pH-metric experiments in the case of copper(II). These studies also provided evidence that ascorbic acid is coordinated to the metal center in its monoprotonated form. Because of relatively fast redox reactions between iron(III) and ascorbic acid, similar studies to confirm the formation of [Fe(HA)]2+ were not feasible. However, indirect kinetic evidence also supported the formation of the [M(HA)](" 1>+ complex in both systems (6). 

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. 

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). 

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 the absence and presence of PVP, on increasing concentration of the ascoibic acid, the reaction rate was found to increase in all experiments. Moreover, it was also fonnd to increase on increasing concentration of ascorbic acid for a fixed copper (II) ion concentration (Figs. 35.4 and 35.5). 

From these results it can be said that presence of PVP in pH 4.50 solution definitely causes to decrease in the copper (II) ion catalyzed oxidation reaction rate of ascorbic acid. 

Experimental observations indicate that the oxidation of cobalt (II) to cobalt (III) and the formation of ethylenediamine from N-hydroxyethylethylene-diamine occur simultaneously. This is quite the opposite to what is usually assumed in other instances of transition metal catalysis of organic reactions—for example, the catalytic effect of manganese in the oxidation of oxalic acid (7, 8), of iron in the oxidation of cysteine to cystine (22) and of thioglycolic acid to dithioglycolic acid (5, 23), of copper in the oxidation of pyrocatechol to quinone and in the oxidation of ascorbic acid (29, 30), and of cobalt in the oxidation of aldehydes and unsaturated hydrocarbons (4). In all these reactions the oxidation of the organic molecule occurs by the abstraction of an electron by the oxidized form of the metal ion. 

The superoxo-containing species [(NC)6Co(/u.-02)Co(CN5]5 can be reduced with thiols such as 2-aminoethanethiol or L-cysteine (175), and the reduction reaction is catalyzed by copper(II) ions in aqueous solution. When copper(II) is present, the role of the thiol is to reduce cop-per(II) to copper(I), which then reacts with the superoxo species through an inner-sphere mechanism. Conversely, when the superoxo complex [(H3N)5Co(/x-02)Co(NH3)5]5+ is reduced with thiol (176), the reaction follows an outer-sphere mechanism, as would be expected. Ascorbic acid also reduces both complexes (177), but only the reduction of the cyano-containing complex exhibits copper(II) catalysis. 

All the internal monooxygenases that have so far been purified and characterized contain flavin coenzymes. The external hydrogen donors include reduced NAD, reduced NADP, ascorbic acid and sulfhydryl compounds. Cofactors required for the external monooxygenases are flavin, pteridine, copper, nonheme iron and heme as cytochrome P-450. In some monooxygenase reactions, enzymes and/or electron carrier systems other than monooxygenase itself are involved in the transfer of an electron or hydrogen from the external hydrogen donor to the cofactor involved. 

However, its presence is not the only determinant of whether or not oxidative deterioration occurs. Olson and Brown (1942) showed that washed cream (free of ascorbic acid) from susceptible milk did not develop an oxidized flavor when contaminated with copper and stored for three days. Subsequently, the addition of ascorbic acid to washed cream, even in the absence of added copper, was observed to promote the development of an oxidized flavor (Pont 1952). Krukovsky and Guthrie (1945) and Krukovsky (1961) reported that 0.1 ppm added copper did not promote oxidative flavors in milk or butter depleted of their Vitamin C content by quick and complete oxidation of ascorbic acid to dehydroascorbic acid. Krukovsky (1955) and Krukovsky and Guthrie (1945) further showed that the oxidative reaction in ascorbic acid-free milk could be initiated by the addition of ascorbic acid to such milk. Accordingly, these workers and others have concluded that ascorbic acid is an essential link in a chain of reactions resulting in the development of an oxidized flavor in fluid milk. 

King (1963) theorized that when the initial concentration of ascorbic acid increases beyond that necessary to saturate the copper in the system, the oxidation of ascorbic acid becomes so rapid and the products of the reaction accumulate so rapidly that they either block the reaction involving the lipids in the system or prevent the copper from acting as a catalyst. 

Haase and Dunkley (1969B) reported that although high concentrations of ascorbic acid in model systems of potassium linoleate were prooxidant, a decrease in the rate of oxidation was observed. Haase and Dunkley (1969C) further noted that certain concentrations of ascorbic acid and copper inhibited the formation of conjugated dienes, but not the oxidation of ascorbic acid, and caused a rapid loss of part of the conjugated dienes already present in the system. They theorized that certain combination concentrations of ascorbic acid and copper inhibit oxidation by the formation of free radical inhibitors which terminate free- radical chain reactions, and that the inhibitors are complexes that include the free radicals. 

In its biochemical functions, ascorbic acid acts as a regulator in tissue respiration and tends to serve as an antioxidant in vitro by reducing oxidizing chemicals. The effectiveness of ascorbic acid as an antioxidant when added to various processed food products, such as meats, is described in entry on Antioxidants. In plant tissues, the related glutathione system of oxidation and reduction is fairly widely distributed and there is evidence that election transfer reactions involving ascorbic acid are characteristic of animal systems. Peroxidase systems also may involve reactions with ascorbic acid In plants, either of two copper-protein enzymes are commonly involved in the oxidation of ascorbic acid. 

Vitamin C [ascorbic acid) Men 90 mg/d Women 75 mg/d Cofactor for reactions requiring reduced copper or iron met-alloenzyme and as a protective antioxidant prevents scurvy Gastrointestinal disturbances, kidney stones, excess iron absorption... 

The radical form 9.4 has an unpaired electron and may undergo fast reactions with redox partners that also undergo one-electron processes. Such a redox partner is the triplet radical, dioxygen. The copper complex of ascorbic acid undergoes rapid aerial oxidation to give the dione, dehydroascorbic acid, which may be viewed as being derived by electron loss from the radical (Fig. 9-4). 

Figure 9-4. The reaction of dioxygen with the copper complex of ascorbic acid generates a copper complex of dehydroascorbic acid.

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