Heme‐(hydro)peroxide mediated O‐ and N‐dealkylation

Abstract

The mechanism of microperoxidase-8 (MP-8) mediated O-and N-dealkylation was investigated. In the absence of ascorbate (peroxidase mode), many unidentified polymeric products are formed and the extent of substrate degradation correlates (r 0.94) with the calculated substrate ionization potential, reflecting the formation of radical intermediates.In the presence of ascorbate (P450 mode) formation of polymeric products is largely prevented but, surprisingly, dealkylation is not affected. In addition, aromatic hydroxylation and oxidative dehalogenation is observed. The results exclude a radical mechanism and indicate the involvement of a (hydro)peroxo-iron heme intermediate in P450-type of heteroatom dealkylation.

Elucidation of theipso-Substitution Mechanism for Side-Chain Cleavage of α-Quaternary 4-Nonylphenols and 4-t-Butoxyphenol inSphingobium xenophagumBayram

“…7), and several enzymatic systems are known to detach electron-donating as well as electron-withdrawing substituents (3,7,10,19,22,24,30,39,42). However, most studies that consider cationic leaving groups refer to hydrogen substituents (3,7,10,19,22,24), and it was only recently proposed that ␣-quaternary alkyl side chains are able to detach in this way (6,14,39). In growth and O 2 -monitoring experiments, S. xenophagum Bayram was able to act upon both ␣-quaternary 4-alkylphenols and 4-alkoxyphenols (Fig.…”

“…1, pathways 1 and 2]). ipso-Substitution has also been proposed for enzymatic cleavage of alkoxyphenols (3,18,26,27). In contrast to oxidative O dealkylation, a well-known metabolic pathway for ether compounds involving hydroxylation of the carbon atom in ␣-position to the ether oxygen (9, 21), ipso-substitution is able to operate on aryl ether structures without ␣-hydrogens, such as 4-aryloxyphenols (29).…”

Microperoxidase 8 catalyzed nitration of phenol by nitrogen dioxide radicals

“…In conclusion, our results describe that besides the oxidation of typical peroxidase cosubstrates [2±4], the para-hydroxylation of aniline [5], the monooxygenation of polycyclic aromatic compounds [6], the S-oxidation of sulfides [7], and N-and O-dealkylation reactions [8], MP8 is able to catalyze another type of reaction: the nitration of aromatic compounds like phenol by nitrite in the presence of H 2 O 2 at room temperature and neutral pH. This new activity of MP8 first opens a new access to nitro-aromatic compounds under mild conditions and, because the nitration of l-tyrosine into 3-nitro-l-tyrosine is also observed, it further validates the use of this minienzyme as a model for heme peroxidases, especially to mimick the reactions of NO-derived species such as nitrite and NO 2 X with lipids [16], proteins [17±19], nucleic acids [20], mediators [21] and drugs [22] under oxidative stress conditions.…”

“…First of all, MP8 shows a peroxidase-like activity and is able to perform the oxidation of several typical peroxidase cosubstrates like o-dianisine [2], guaiacol [3], 2,2 H -azinobis(3-ethylbenzo-6-thiazolinesulfonic acid) (ABTS) [4]. Second, MP8 also shows a cytochrome P450-like activity and catalyzes the para-hydroxylation of aniline [5], the monooxygenation of polycyclic aromatic compounds [6], the S-oxidation of sulfides [7], and the Nand O-dealkylation of aromatic amines and ethers [8]. In addition, MP8 has also recently been shown to be able to oxidize N-monosubstituted hydroxylamines with formation of very stable iron(II)-nitrosoalkane complexes [9].…”

Can peroxygenase and microperoxidase substitute cytochrome P450 in biosensors

“…In the literature, there are many publications describing the peroxide-dependent P450 analogous and peroxidatic activities of microperoxidases in homogeneous solution [66,[80][81][82][83][84][85][86][87][88][89]. The peroxidatic efficiency of microperoxidases for the oxidation of typical phenolic substrates as expressed by k cat /K M is almost 100 times lower than the value for HRP [90].…”