Mechanism of reaction of horseradish peroxidase with chlorite and chlorine dioxide

Mechanism of and exquisite selectivity for O–O bond formation by the heme-dependent chlorite dismutase

“…Further, even in the presence of a large excess of the appropriate diagnostic cosubstrates, dismutation is overwhelmingly favored over oxidation, halogenation, or oxygenation chemistry Table S2). This indicates that these substrates do not combine with potential reactive intermediates at the active site; nor do reactive ClO Ϫ / HClO or ClO 2 escape from the enzyme during catalysis (Scheme S1) (8). Given the variety of known reactions catalyzed by heme and heme/chlorite systems, such specificity is extraordinary.…”

“…Like HRP, Cld could oxidize chlorite by one electron to generate chlorine dioxide (ClO 2 ), which readily chlorinates MCD in an uncatalyzed fashion (8 (14). Last, Cld could use chlorite to generate ClO Ϫ /HClO (pK a Ϸ 7.5).…”

“…In the presence of a large excess of chlorite and 100 M MCD, conditions resulting in stoichiometric chlorination (via ClO 2 ) by HRP (8), no Cld-mediated chlorination is observed. Under the same conditions and with a halogen anion (Cl Ϫ , Br Ϫ , I Ϫ ) in excess, no halogenation was observed.…”

“…Heme peroxidases use chlorite as an oxidant in one-electron oxidation (8), oxygen atom transfer (OAT) (9), and chlorination chemistry (10,11). Ferric horseradish peroxidase (HRP) and cytochrome P450 react with chlorite to generate the reactive ferryl porphyrin cation radical (compound I) intermediate (8,11).…”

Chlorite reactivity with myoglobin: Analogy with peroxide and nitrite chemistry?

“…Recently, Obinger et al demonstrated that chlorite induces the two-electron oxidation of ferric HRP to Compound I with the release of hypochlorous acid, and can also reduce both Compound I and Compound II, generating chlorine dioxide. These reaction products (hypochlorus acid and chlorine dioxide), known to induce heme destruction, can also compete with chlorite for binding to the ferric HRP and mediate Compound I formationbut are not able to react with Compounds I and II [7]. Chlorite high spin complexes are generated either for the mammalian myeloperoxidase (MPO) and lactoperoxidase (LPO) in their reaction with sodium chlorite, but this system, contrary to HRP and CPO, is not able to chlorinate a molecule [8].…”