Reactions of Iron(III) Porphyrins with Oxidants. Structure-Reactivity Studies

Traylor, Teddy G.; Kim, Cheal; Richards, Joseph L.; Xu, Feng; Perrin, Charles L.

doi:10.1021/ja00117a015

Cited by 146 publications

(113 citation statements)

References 1 publication

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“…This pathway is similar to that catalysed by haem oxygenase except that the billirubin intermediate is rapidly converted to colourless dipyrrolic fragments [25]. Chelation of the haem moiety has been shown to prevent the formation of the ferryl intermediate [12,14] and would be expected to decrease the rate of haem destruction. The polymerization of haem molecules to form β-haematin (the form of haem in haemozoin) involves the formation of a non-covalent co-ordination complex with the ferric iron of each haem moiety chelated onto a carboxy side chain of the adjacent moiety [22,32].…”

Section: Haem Undergoes Peroxidative Decompositionmentioning

confidence: 83%

“…In addition, haem can undergo peroxidative reactions that destroy the porphyrin ring [12,13]. The enzyme-like activities of haem have been extensively studied as models for haem-containing enzymes [14,15]. We have re-examined the catalytic activities of haem, under conditions designed to resemble those found in the food vacuole, and have found that they could contribute significantly to the degradation of haem and to the breakdown of reactive oxygen species.…”

Section: Abbreviations Used : 8ac6 Nnh-bis-(4-o[4-(diethylamino)-1-mentioning

confidence: 99%

“…The peroxidative degradation of haem is thought to involve a reaction with H # O # to form a ferryl intermediate [14,25] (Scheme 1B, reaction c). Transfer of electrons within the Fe(IV) intermediate of haem results in the opening of the porphyrin ring (Scheme 1B, reaction c).…”

Section: Haem Undergoes Peroxidative Decompositionmentioning

confidence: 99%

“…Hostderived catalase may be important in this process as this enzyme remains active at pH 5, however, host glutathione peroxidase would have very little activity under the conditions of the food vacuole [40,41]. Another possible route for H # O # breakdown comes from the observation that haem itself can decompose H # O # via a catalase-like activity [14,15] (Scheme 1B, reaction a). We have re-examined the catalase-like activity of haem under food vacuole conditions ( Figure 3A).…”

Section: Haem Also Displays Catalase-like and Peroxidase-like Activitmentioning

confidence: 99%

“…Free haem has also been reported to display peroxidase-like activity against oxidizable substrates [14,44] (Scheme 1B, reaction b). We found that haem is an efficient catalyst of the oxidation of OPD under conditions which mimic those of the food vacuole ( Figure 4A).…”

Section: Haem Also Displays Catalase-like and Peroxidase-like Activitmentioning

confidence: 99%

See 4 more Smart Citations

Inhibition of the peroxidative degradation of haem as the basis of action of chloroquine and other quinoline antimalarials

Loria

Miller

Foley

et al. 1999

Biochemical Journal

191

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The malaria parasite feeds by degrading haemoglobin in an acidic food vacuole, producing free haem moieties as a by-product. The haem in oxyhaemoglobin is oxidized from the Fe(II) state to the Fe(III) state with the consequent production of an equimolar concentration of H2O2. We have analysed the fate of haem molecules in Plasmodium falciparum-infected erythrocytes and have found that only about one third of the haem is polymerized to form haemozoin. The remainder appears to be degraded by a non-enzymic process which leads to an accumulation of iron in the parasite. A possible route for degradation of the haem is by reacting with H2O2, and we show that, under conditions designed to resemble those found in the food vacuole, i.e., at pH 5.2 in the presence of protein, free haem undergoes rapid peroxidative decomposition. Chloroquine and quinacrine are shown to be efficient inhibitors of the peroxidative destruction of haem, while epiquinine, a quinoline compound with very low antimalarial activity, has little inhibitory effect. We also show that chloroquine enhances the association of haem with membranes, while epiquinine inhibits this association, and that treatment of parasitized erythrocytes with chloroquine leads to a build-up of membrane-associated haem in the parasite. We suggest that chloroquine exerts its antimalarial activity by causing a build-up of toxic membrane-associated haem molecules that eventually destroy the integrity of the malaria parasite. We have further shown that resistance-modulating compounds, such as chlorpromazine, interact with haem and efficiently inhibit its degradation. This may explain the weak antimalarial activities of these compounds.

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Section: Haem Undergoes Peroxidative Decompositionmentioning

confidence: 83%

Section: Abbreviations Used : 8ac6 Nnh-bis-(4-o[4-(diethylamino)-1-mentioning

confidence: 99%

Section: Haem Undergoes Peroxidative Decompositionmentioning

confidence: 99%

Section: Haem Also Displays Catalase-like and Peroxidase-like Activitmentioning

confidence: 99%

Section: Haem Also Displays Catalase-like and Peroxidase-like Activitmentioning

confidence: 99%

See 3 more Smart Citations

Inhibition of the peroxidative degradation of haem as the basis of action of chloroquine and other quinoline antimalarials

Loria

Miller

Foley

et al. 1999

Biochemical Journal

191

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show abstract

Cytochrome P-450 model reaction: effects of substitution on the rate of aromatic hydroxylation

Safari

Bahadoran

Hoseinzadeh

et al. 2000

J. Porphyrins Phthalocyanines

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The study of haemin-catalysed oxidation reactions was extended to substituted aromatic rings. Both electron-donating and electron-withdrawing substituents on aromatic rings act as para- and meta-directing agents in the presence of tetrakis(2,6-dichlorophenyl)porphyrin iron(III) chloride as catalyst and m-chloroperbenzoic acid as oxidant. A new kinetic method for measuring relative rates of epoxidation of alkenes and related compounds has been developed; while steric hindrance results in decreasing the rate of hydroxylation, electron-rich and electron-withdrawing substituents were found to increase the rate of hydroxylation. A linear relationship between the logarithm of the relative rate of hydroxylation and σ Hammet is obtained, although electron-donating and electron-withdrawing substituents fit separate lines. Addition of pyridine to haemin was shown to increase the yield of epoxidation but decrease the yield of aromatic hydroxylation.

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Cytochrome P‐450 model reaction: effects of substitution on the rate of aromatic hydroxylation

Safari¹,

Bahadoran²,

Hoseinzadeh³

et al. 2000

J. Porphyrins Phthalocyanines

View full text Add to dashboard Cite

Reactions of Iron(III) Porphyrins with Oxidants. Structure-Reactivity Studies

Cited by 146 publications

References 1 publication

Inhibition of the peroxidative degradation of haem as the basis of action of chloroquine and other quinoline antimalarials

Inhibition of the peroxidative degradation of haem as the basis of action of chloroquine and other quinoline antimalarials

Cytochrome P-450 model reaction: effects of substitution on the rate of aromatic hydroxylation

Cytochrome P‐450 model reaction: effects of substitution on the rate of aromatic hydroxylation

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