Heterolytic cleavage of peroxides

Peroxides can cleave heterolytically and homolytically. Heterolytic cleavage of peroxides results in formation of ions. 

The positive charge on the proximal His 170 facilitates the formation of the iron-peroxide bond. Thus, inversion of the charge properties at the active site of HRP facilitates the heterolytic cleavage of the 0-0 bond. The positive charges on His 42 and Arg 38 and the negative charge on His 170 assist the formation of the Fe = 0 species. 

Some of these ideas incorporating a pterin radical are outlined in Fig. 9. Here the pterin serves as an electron donor to the oxy intermediate to give the peroxy di-anion. The substrate, L-Arg, itself serves as the proton donor to the peroxo intermediate as proposed by Crane et al. (80), which is required for heterolytic cleavage of the peroxide 0—0 bond. The proton delivery machinery outlined in Fig. 9 could also help to explain why peroxide itself cannot support the conversion of L-Arg to N°-hydroxy-L-Arg (126). The reaction may require a potent base like... 

In the case of cytochrome P450, it has been proposed that 0-0 bond cleavage precedes attack on substrate (22). It is generally believed that this cleavage is heterolytic, although homolytic cleavage of peroxide derivatives by cytochrome P450 has also been observed (23). 

It may be reasonable to argue that this further activation is achieved in several ways. The acid-catalysis required for Gal and de Bruin complex [Rh(/c -bpa)(cod)](PF6) to react with dioxygen can be used to protonate the peroxo compoimd (Scheme 10) to a hydroperoxo species. This is a way to achieve further activation of dioxygen, since it decreases the nucleophilic character of the peroxo hgand and makes interaction with the coordinated olefin easier. Recent works by Moro-oka [88,89] and Braun [90] (Scheme 15) have shown that peroxorhodium complexes can be protonated to hydroperoxo compounds. However, the addition of a second mole of acid leads to hydrogen peroxide ehmination rather than to the highly electrophilic oxo species (M = O) that could result from the heterolytic cleavage of the O - O bond with removal of water. 

The initial presence of a dimeric species may explain the dependence of the rate on the square root of the concentration of [Co(A2ODC)]2+. Subsequent heterolytic cleavage of the Co-OH bond affords the Co+ complex and hydrogen peroxide. 

Figure 1.6 Minimal catalytic scheme of VCPO based on crystal structures of the native enzyme and the peroxo-intermediate (Messerschmidt ef a/. 1997). Lys353 is considered to be crucial in assisting heterolytic cleavage of the side-on bound peroxide. EPR and V-EXAFS data suggest that the enzyme remains in the oxidation state throughout the cycle. Source Hasan, Z., Renirie, R., Kerkman, R., Ruijssenaars, H.J., Hartog, A.F. and Wever, R. (2006). Journal of Biological Chemistry, 281, 9738-9744. Reprinted with permission from Renirie, R., Hemrika, W., Piersma, S.R. and Wever, R. (2000). Biochemistry, 39, 11 33-1141. Copyright 2000 American Chemical Society.

Little is known about the peroxide activation process in BCcPs. However, the NEP structure revealed a peroxidebinding site quite different from the more traditional peroxidases. BCcPs do not have a distal His that serves as the catalytic acid-base required for heterolytic cleavage of the peroxide 0-0 bond. The NEP structure has a Glu residue directly adjacent to the peroxide-binding site that most likely operates as the acid-base catalyst. The only other peroxidase known to have a Glu in this position is chloroperoxidase. " ... 

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