One-Electron Oxidation of 6-Substituted Benzo[a]pyrenes by Manganic Acetate. A Model for Metabolic Activation

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Radical cations of benzo[α]pyrene (BP) and 6-substituted derivatives were generated by one-electron oxidation with 2 equiv of Mn(OAc)3.2H2O. Some of the properties of these radical cations were investigated by nucleophilic trapping with acetate ion. BP produced predominantly 6-OAcBP and small amounts of BP 1,6-, 3,6-, and 6,12-dione. 6-FBP yielded 6-OAcBP, a mixture of l,6-(OAc)2BP and 3,6-(OAc)2BP, and BP diones. In the case of 6-C1BP and 6-BrBP the major products obtained were a mixture of the 1-OAc and 3-OAc derivatives, and BP diones, while substantial starting material remained unreacted. 6-CH3BP afforded mostly 6-OAcCH2BP, a mixture of 1-OAc and 3-OAc derivatives of 6-CH3BP, and a mixture of 1-OAc and 3-OAc derivatives of 6-OAcCH2BP. These results indicate that nucleophilic substitution of BP,+and 6-FBP.+occurs exclusively at C-6. For 6-ClBP-+and 6-BrBP*+substitution at C-l and C-3, which are the positions of second highest charge density in their radical cations after C-6, compete successfully for nucleophilic substitution. For 6-CH3BP'+charge localization at C-6 activates the methyl group rendering it the most reactive toward nucleophilic attack. Competitive acetoxylation of 6-CH3BP.+ also occurs to a minor extent at C-l and C-3. These mechanistic studies have been useful in clarifying some aspects of the metabolism of BP and its halogeno derivatives by cytochrome P-450 and peroxidases. Furthermore, this chemistry can provide some guidance in understanding the mechanism of tumor initiation by these compounds.

Original languageEnglish (US)
Pages (from-to)3561-3570
Number of pages10
JournalJournal of Organic Chemistry
Volume54
Issue number15
DOIs
StatePublished - Jul 1 1989

Fingerprint

Benzo(a)pyrene
Acetates
Chemical activation
Derivatives
Oxidation
Electrons
Cations
Substitution reactions
Peroxidases
Charge density
Metabolism
Cytochrome P-450 Enzyme System
Tumors
Ions

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

One-Electron Oxidation of 6-Substituted Benzo[a]pyrenes by Manganic Acetate. A Model for Metabolic Activation. / Cremonesi, Paolo; Cavalieri, Ercole; Rogan, Eleanor G.

In: Journal of Organic Chemistry, Vol. 54, No. 15, 01.07.1989, p. 3561-3570.

Research output: Contribution to journalArticle

@article{9519599584f74d8291daf02cd2633fc9,
title = "One-Electron Oxidation of 6-Substituted Benzo[a]pyrenes by Manganic Acetate. A Model for Metabolic Activation",
abstract = "Radical cations of benzo[α]pyrene (BP) and 6-substituted derivatives were generated by one-electron oxidation with 2 equiv of Mn(OAc)3.2H2O. Some of the properties of these radical cations were investigated by nucleophilic trapping with acetate ion. BP produced predominantly 6-OAcBP and small amounts of BP 1,6-, 3,6-, and 6,12-dione. 6-FBP yielded 6-OAcBP, a mixture of l,6-(OAc)2BP and 3,6-(OAc)2BP, and BP diones. In the case of 6-C1BP and 6-BrBP the major products obtained were a mixture of the 1-OAc and 3-OAc derivatives, and BP diones, while substantial starting material remained unreacted. 6-CH3BP afforded mostly 6-OAcCH2BP, a mixture of 1-OAc and 3-OAc derivatives of 6-CH3BP, and a mixture of 1-OAc and 3-OAc derivatives of 6-OAcCH2BP. These results indicate that nucleophilic substitution of BP,+and 6-FBP.+occurs exclusively at C-6. For 6-ClBP-+and 6-BrBP*+substitution at C-l and C-3, which are the positions of second highest charge density in their radical cations after C-6, compete successfully for nucleophilic substitution. For 6-CH3BP'+charge localization at C-6 activates the methyl group rendering it the most reactive toward nucleophilic attack. Competitive acetoxylation of 6-CH3BP.+ also occurs to a minor extent at C-l and C-3. These mechanistic studies have been useful in clarifying some aspects of the metabolism of BP and its halogeno derivatives by cytochrome P-450 and peroxidases. Furthermore, this chemistry can provide some guidance in understanding the mechanism of tumor initiation by these compounds.",
author = "Paolo Cremonesi and Ercole Cavalieri and Rogan, {Eleanor G}",
year = "1989",
month = "7",
day = "1",
doi = "10.1021/jo00276a013",
language = "English (US)",
volume = "54",
pages = "3561--3570",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "15",

}

TY - JOUR

T1 - One-Electron Oxidation of 6-Substituted Benzo[a]pyrenes by Manganic Acetate. A Model for Metabolic Activation

AU - Cremonesi, Paolo

AU - Cavalieri, Ercole

AU - Rogan, Eleanor G

PY - 1989/7/1

Y1 - 1989/7/1

N2 - Radical cations of benzo[α]pyrene (BP) and 6-substituted derivatives were generated by one-electron oxidation with 2 equiv of Mn(OAc)3.2H2O. Some of the properties of these radical cations were investigated by nucleophilic trapping with acetate ion. BP produced predominantly 6-OAcBP and small amounts of BP 1,6-, 3,6-, and 6,12-dione. 6-FBP yielded 6-OAcBP, a mixture of l,6-(OAc)2BP and 3,6-(OAc)2BP, and BP diones. In the case of 6-C1BP and 6-BrBP the major products obtained were a mixture of the 1-OAc and 3-OAc derivatives, and BP diones, while substantial starting material remained unreacted. 6-CH3BP afforded mostly 6-OAcCH2BP, a mixture of 1-OAc and 3-OAc derivatives of 6-CH3BP, and a mixture of 1-OAc and 3-OAc derivatives of 6-OAcCH2BP. These results indicate that nucleophilic substitution of BP,+and 6-FBP.+occurs exclusively at C-6. For 6-ClBP-+and 6-BrBP*+substitution at C-l and C-3, which are the positions of second highest charge density in their radical cations after C-6, compete successfully for nucleophilic substitution. For 6-CH3BP'+charge localization at C-6 activates the methyl group rendering it the most reactive toward nucleophilic attack. Competitive acetoxylation of 6-CH3BP.+ also occurs to a minor extent at C-l and C-3. These mechanistic studies have been useful in clarifying some aspects of the metabolism of BP and its halogeno derivatives by cytochrome P-450 and peroxidases. Furthermore, this chemistry can provide some guidance in understanding the mechanism of tumor initiation by these compounds.

AB - Radical cations of benzo[α]pyrene (BP) and 6-substituted derivatives were generated by one-electron oxidation with 2 equiv of Mn(OAc)3.2H2O. Some of the properties of these radical cations were investigated by nucleophilic trapping with acetate ion. BP produced predominantly 6-OAcBP and small amounts of BP 1,6-, 3,6-, and 6,12-dione. 6-FBP yielded 6-OAcBP, a mixture of l,6-(OAc)2BP and 3,6-(OAc)2BP, and BP diones. In the case of 6-C1BP and 6-BrBP the major products obtained were a mixture of the 1-OAc and 3-OAc derivatives, and BP diones, while substantial starting material remained unreacted. 6-CH3BP afforded mostly 6-OAcCH2BP, a mixture of 1-OAc and 3-OAc derivatives of 6-CH3BP, and a mixture of 1-OAc and 3-OAc derivatives of 6-OAcCH2BP. These results indicate that nucleophilic substitution of BP,+and 6-FBP.+occurs exclusively at C-6. For 6-ClBP-+and 6-BrBP*+substitution at C-l and C-3, which are the positions of second highest charge density in their radical cations after C-6, compete successfully for nucleophilic substitution. For 6-CH3BP'+charge localization at C-6 activates the methyl group rendering it the most reactive toward nucleophilic attack. Competitive acetoxylation of 6-CH3BP.+ also occurs to a minor extent at C-l and C-3. These mechanistic studies have been useful in clarifying some aspects of the metabolism of BP and its halogeno derivatives by cytochrome P-450 and peroxidases. Furthermore, this chemistry can provide some guidance in understanding the mechanism of tumor initiation by these compounds.

UR - http://www.scopus.com/inward/record.url?scp=0001589183&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0001589183&partnerID=8YFLogxK

U2 - 10.1021/jo00276a013

DO - 10.1021/jo00276a013

M3 - Article

AN - SCOPUS:0001589183

VL - 54

SP - 3561

EP - 3570

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 15

ER -