Chloroperoxidase Compound

Chloroperoxidase (CPO) is one of the most versatile heme enzymes. In addition to its biological function to catalyze the hydrogen peroxide-dependent chlorination of cyclopentanedione during the biosynthesis of the antibiotic caldarioymcin [20, 21], CPO halogenates a wide range of substrates and has 

Compound I can oxidize a chloride anion and has been proposed to form an Fe(III)-hypohalite intermediate [27]. However, it has not yet been entirely resolved whether this hypohalite intermediate directly chlorinates the organic substrate [28], or whether HOCl is released upon protonation of the intermediate and free HOCl or CI2 performs the chlorination reactions [29]. Interestingly, it has been shown by extended X-ray absorption fine structure (EXAFS) spectroscopy that the ferryl form is consistent with a protonated 0x0 species, which agrees well with density functional calculations on an Fe(IV)-OH species [30]. 

CPO has served as an important model system for the study of reaction intermediates of P450 enzymes because of their significantly longer hfetimes, greatly facilitating their study. This is particularly true for the high-valent intermediate compound I and its one-electron-reduced form compound II. Another common short-lived reaction intermediate is the ferric hydroperoxo intermediate 

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Kim SH, Perera R, Hager LP, Dawson JH, Hoffman BM (2006) Rapid Freeze-Quench ENDOR Study of Chloroperoxidase Compound I The Site of the Radical. J Am Chem Soc 128 5598... 

Green MT, Dawson JH, Gray HB (2004) OxoironflV) in chloroperoxidase compound II is basic implications for P450 chemistry. Science 304 1653-1656... 

Mossbauer spectra has been extensively used to probe the structure of the iron nucleus in biological FeIV=0 compounds. These include horseradish peroxidase compoundl[134,180,181], horseradish peroxidase compound II [182,183], horseradish peroxidase compound X [181], Japanese-radish peroxidase compounds I and II [184], chloroperoxidase compound I [185], cytochrome c peroxidase compound I [186] and ferryl myoglobin [183]. Examples of Mossbauer spectra attributed to non-porphyrin-bound FeIV are only available from synthetic model compounds. These include compounds with [130] and without [4-8] an FeIV=0 bond. 

The absorption spectrum of the Compound I form of chloroperoxidase is different from that of horseradish peroxidase Compound I, and is more closely analogous to that of catalase Compound I. This suggests that it may also have a Aiu ground state [22, 50]. However, the EPR spectrum of chloroperoxidase Compound I indicates that there is electron density at the meso carbons this finding is inconsistent with a Ai ground electronic state [50, 93]. Thus, the different absorption spectral properties of the Compound I intermediates of peroxidases may not derive solely from differences in orbital symmetry. Rather, other factors such as the nature of the axial ligand or the macrocycle stereochemistry may be responsible for these spectral differences. 

Kuhnel K, Derat E, Temer J, Shaik S, Schlichting I (2007) Structure and quantum chemical characterization of chloroperoxidase compound 0, a common reaction intermediate of diverse heme enzymes. Proc Natl Acad Sci U S A 104 99-104... 

Palcic MM, Rutter R, Araiso T, Hager LP, Dunford HB (1980) Spectrum of chloroperoxidase compound I. Biochem Biophys Res Commun 94 1123-1127... 

Rutter R, Hager LR Dhonau H, Hendrich M, Valentine M, Debrunner P (1984) Chloroperoxidase compound I electron paramagnetic resonance and Mossbauer studies. Biochemistry 23 6809-6816... 

The one-pot conversions of oximes to gem-halonitro compounds have been achieved by using A(/V,/V.-trihalo-l,3,5-triazines,131 chloroperoxidase in the presence of hydrogen peroxide and potassium chloride,132 or commercial OXONE and sodium chloride.133 Of these methods, the case of OXONE may be the most convenient (Eq. 2.65). 

Taurog et al. [216] showed that contrary to previous suggestions, both iodination and coupling are catalyzed by the oxoferryl porphyrin Tr-cation radical of TPO Compound I and not the oxoferryl protein radical. HRP catalyzed the oxidation of bisulfite to sulfate with the intermediate formation of sulfur trioxide radical anion S03 [217] HPO, MPO, LPO, chloroperoxidase, NADH peroxidase, and methemoglobin oxidized cyanide to cyanyl radical [218],... 

EXAFS data indicated an Fe=0 bond length of 1.65 0.05 A, similar to that found for compound I intermediates in several enzymes such as catalases, horseradish peroxidase, cytochrome c peroxidase, and chloroperoxidases. 

Fig. 18. Mechanisms of compound I formation in type B catalases (based on yeast CCP) (see also Section IV,F and Fig. 7) (A) type A catalases (B) and chloroperoxidase (C).

Reverse micellar systems were shown to be useful for obtaining sulfur-free coal. Chloroperoxidase in AOT/isooctane-RMs was demonstrated as a versatile catalyst for sulfoxidation of aliphatic and aromatic sulfur-containing model coal compounds [341]. 

X-ray absorption spectroscopy has revealed the formation of organochlorine compounds from chloride and chloroperoxidase in weathering plant material (172-174). Moreover, this technique has uncovered the bromide-to-organobromine conversion in environmental samples (174). In addition to chloroperoxidase mediated chlorination, the abiotic chlorination in soils and sediments involving the alkylation of halides during Fe(III) oxidation of natural organic phenols in soils and sediments has been discovered (175-177). 

All three chloroacetic acids (chloroacetic acid [MCA], dichloroacetic acid [DCA], and trichloroacetic acid [TCA]) are naturally occurring (7), with TCA being identified in the environment most frequently (reviews (278, 405 108)). However, these chlorinated acetic acids also have anthropogenic sources. The major source of natural TCA appears to be the enzymatic (chloroperoxidase) or abiotic degradation of humic and fulvic acids, which ultimately leads to chloroform and TCA. Early studies (409) and subsequent work confirm both a biogenic and an abiotic pathway. Model experiments with soil humic and fulvic acids, chloroperoxidase, chloride, and hydrogen peroxide show the formation of TCA, chloroform, and other chlorinated compounds (317, 410-412). Other studies reveal an abiotic source of TCA (412, 413). 

Hoekstra EJ, Lassen P, van Leeuwen JGE, de Leer EWB, Carlsen L (1995) Formation of Organic Chlorine Compounds of Low Molecular Weight in the Chloroperoxidase-Mediated Reaction Between Chloride and Humic Material. In Grimvall A, de Leer EWB (eds) Naturally-Produced Organohalogens. Kluwer, Dordrecht, p 149... 

Zhang R, Nagraj N, Lansakara-P DSP, Hager LP, Newcomb M (2006) Kinetics of Two-Electron Oxidations by the Compound I Derivative of Chloroperoxidase, A Model for Cytochrome P450 Oxidants. Org Lett 8 2731... 

Alvarez RG, Hunter IS, Suckling CJ, Thomas M, Vitinius U (2001) A Novel Biotransformation of Benzofiirans and Related Compounds Catalysed by a Chloroperoxidase. Tetrahedron 57 8581... 

Zaks A, Yabannavar AV, Dodds DR, Evans CA, Das PR, Malchow R (1996) A Novel Application of Chloroperoxidase Preparation of gem-Halonitro Compounds. J Org Chem 61 8692... 

Longoria A, Tinoco R, Vazquez-Duhalt R (2008) Chloroperoxidase-Mediated Transformation of Highly Halogenated Monoaromatic Compounds. Chemosphere 72 485... 

Previously proposed mechanisms of the biosynthesis of certain chlorinated compounds have invoked electrophilic bromination of alkenes followed by passive chloride attack [62], Although this mechanism could explain the origin of adjacent brominated and chlorinated carbons, it does not readily account for compounds containing chlorine only. Thus, with the discovery of chloroperoxidase activity of the vanadium enzyme, the origin of specific chlorinated marine natural products can now be addressed. 

Chen H. Hirao H. Derat E. Schlichting I. Shaik S. Quantum mechanical/molecular mechanical study on the mechanisms of compound I formation in the catalytic cycle of chloroperoxidase an overview on heme enzymes. J. Phys. Chem. B 2008, 112, 9490-9500. 

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