Destruction of cytochrome P-450 by ethylene. Structure of the resulting prosthetic heme adduct.

Montellano, Paul R. Ortiz de; Beilan, Hal S.; Kunze, Kent L.; Mico, Bruce A.

doi:10.1016/s0021-9258(19)69447-0

Cited by 105 publications

(27 citation statements)

References 12 publications

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“…A black precipitate of 1 was obtained by addition of diethyl ether immediately after the disappearance of OEPCo11. The 1H NMR spectrum of 1 shows four singlets at 10.21, 9.88, 9.85, and 9.82 due to the meso protons, indicating the low molecular symmetry. Absorptions due to the formylmethylene moiety appeared at 3.62 and -1.54 as a pair of AB doublets.…”

Section: Resultsmentioning

confidence: 99%

“…10 molar excess) was added to OEPCo" (60 mg) in CHC13 (25 mL), and the reaction was followed spectrophotometrically. The color of the solution turned brown in 1 h. The solution was concentrated at room temperature, and diethyl ether was added to afford a black precipitate of (N,Co-:CHCHO)OEPColnCl (1). When the above reaction was carried out in the presence of acetic acid (0.1 mL), a precipitate of (lV,Co-:CHCHO)OEPCo™OAc (2) was obtained by using petroleum ether instead of diethyl ether.…”

Section: Methodsmentioning

confidence: 99%

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Reaction of (octaethylporphyrinato)cobalt complexes with diazoacetaldehyde. N-(Formylmethyl)- and N-(2-hydroxyethyl)porphyrins

Setsune¹,

Dolphin²

1984

Organometallics

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Reaction of (octaethylporphyrinato)cobalt complexes with diazoacetaldehyde. N-(Formylmethyl)- and N-(2-hydroxyethyl)porphyrins

Setsune¹,

Dolphin²

1984

Organometallics

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“…Aliquots withdrawn from the incubation mixtures after 10, 20, and 30 min were placed in test tubes immersed in ice. The cytochrome P-450 content of the aliquots was measured as before (Ortiz de Montellano & Mico, 1981) on an Aminco DW-2 spectrophotometer. Control incubations were carried out without added substrates and, for each substrate, in the absence of NADPH.…”

Section: Methodsmentioning

confidence: 99%

“…A. Mico, unpublished results). In fact, we have established in one instance that an epoxide competitively inhibits the destructive action of a closely related olefin (Ortiz de Montellano & Mico, 1981). An in-dependent study has also provided evidence that the destruction of cytochrome P-450 by vinyl chloride is not mediated by the corresponding epoxide metabolite (Guengerich & Strickland, 1977).…”

mentioning

confidence: 96%

Destruction of cytochrome P-450 by vinyl fluoride, fluroxene, and acetylene. Evidence for a radical intermediate in olefin oxidation

Montellano¹,

Kunze²,

Beilan³

et al. 1982

Biochemistry

116

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Vinyl fluoride, vinyl bromide, fluroxene (2,2,2-trifluoroethyl vinyl ether), and acetylene alkylate the prosthetic heme group of cytochrome P-450 enzymes which catalyze their metabolism. The alkylated heme moiety has been identified in all four cases, after carboxyl group methylation and demetalation, as the dimethyl easier of N-(2-oxoethyl)protoporphyrin IX. The dimethyl acetal derivative of the aldehyde group in this structure is also isolated. The formation of the same prosthetic heme adduct with the four substrates requires introduction of an oxygen at the trifluoroethoxy or halide-substituted terminus of the pi bond and reaction of the unsubstituted terminus with a heme nitrogen atom. This reaction orientation is consistent with a radical intermediate, possibly formed by way of an initial pi-bond radical cation, but is difficult to reconcile with a cationic intermediate. The occurrence of a radical intermediate in the oxidation of olefins by cytochrome P-450 is thus suggested.

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“…This reduction has been accomplished by the Wolff-Kishner method, with lithium aluminum hydride, with diborane, and by catalytic hydrogenation.2 In addition, diverse 2-benzylpyrroles have been synthesized by the reduction of 2-benzoylpyrroles with sodium borohydride in boiling dioxane3 and with lithium in ammonia4 or by the lithium borohydride or sodium cyanoborohydride reduction of 6-aryl-6-(IV,iV-dialkylamino)-l-azafulvinium salts. 5 Of the reductive methods cited above, the Wolff-Kishner and lithium aluminum hydride processes are the most useful, but the vigorous nature and/or lack of selectivity thereof decreases their scope.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of N-(formylmethyl)protoporphyrin and N-(2-hydroxyethyl)protoporphyrin IX dimethyl esters

Setsune¹,

Dolphin²

1985

J. Org. Chem.

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N-(Formy lmethyl)protoporphyrin IX dimethyl ester zinc chloride and the corresponding dimethyl acetal were synthesized by the electrochemical reduction of N,Co-(formylmethylene) protoporphyrin IX dimethyl ester cobalt(III) chloride. This species, in which the cobalt and a porphyrin nitrogen are bridged by a single carbon atom, was prepared from the reaction of protoporphyrin IX dimethyl ester cobalt(II) with diazoacetaldehyde. IV-(2-Hydroxyethyl)protoporphyrin IX dimethyl ester zinc chloride was obtained by the reduction of the corresponding N-formylmethyl complex with LiAlH(0-t-C4H9)3. The free bases of all of the zinc complexes were obtained by acid-catalyzed demetalation.It has recently been reported that the prosthetic heme of cytochrome P-450 monooxygenases is converted into abnormal green porphyrins during the metabolism of 1,4-dihydropyridine derivatives,1-4 terminal olefins,5 terminal acetylenes,6,7 1-aminotriazole,8 and cyclopropyl amines.9,10 N-Methylprotoporphyrin IX dimethyl ester with the N-methyl group specifically on ring A was characterized for the hepatically derived porphyrin biologically modified by 3,5-dicarbethoxy-l,4-dihydrocollidine on the basis of chemical synthesis and HPLC separation of four possible isomers of (N-methyl)-PPIXDME.2'1

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Destruction of cytochrome P-450 by ethylene. Structure of the resulting prosthetic heme adduct.

Cited by 105 publications

References 12 publications

Reaction of (octaethylporphyrinato)cobalt complexes with diazoacetaldehyde. N-(Formylmethyl)- and N-(2-hydroxyethyl)porphyrins

Reaction of (octaethylporphyrinato)cobalt complexes with diazoacetaldehyde. N-(Formylmethyl)- and N-(2-hydroxyethyl)porphyrins

Destruction of cytochrome P-450 by vinyl fluoride, fluroxene, and acetylene. Evidence for a radical intermediate in olefin oxidation

Synthesis of N-(formylmethyl)protoporphyrin and N-(2-hydroxyethyl)protoporphyrin IX dimethyl esters

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