New adducts of chloroethylene oxide and chloroacetaldehyde with pyrimidine nucleosides

A. Barbin, M. Friesen, I. K. O'Neill, A. Croisy, H. Bartsch

Research output: Contribution to journalArticlepeer-review

Abstract

Pyrimidine nucleosides were treated with chloroethylene oxide (CEO) and 2-chloroacetaldehyde (CAA) in methanol and, following trimethyl-silylation, the products were analysed by combined gas chromatography-mass spectrometry (GC-MS). Reaction of CEO with 2′-deoxycytidine gave 3,N4-etheno-2′-deoxycytidine and diadduct isomers in which a 1-hydroxy-2-chloroethyl group was substituted for hydrogen on either deoxyribose hydroxyl group. When the N-3-position of 2′-deoxycytidine was blocked by a methyl group, CEO or CAA added a 2-chlorovinyl group at the exo-cyclic N4 amino nitrogen, as evidenced by a pair of cis/trans isomers. Reaction of 3-methylcytidine and CEO also gave the cis/trans 2-chlorovinyl base adducts, as well as six isomers with a 1-hydroxy-2-chloroethyl group attached to ribose and nine isomeric diadducts, which are possibly positional and optical isomers. Although CEO and CAA were less reactive towards uracil in 3-methyluridine than to cytosine in 3-methyl(deoxy)-cytidine, both electrophiles were able to alkylate 3-methyluridine on ribose, yielding 1-hydroxy-2-chloroethyl derivatives. These data suggest that CEO and CAA may also yield non-cyclic adducts with cytosine in double-stranded DNA where the N-3 position is of low accessibility. Such adducts are of interest in view of their potential promutagenic properties. The data also imply a new mechanism of reaction of CEO with nucleophiles.

Original languageEnglish (US)
Pages (from-to)43-54
Number of pages12
JournalChemico-Biological Interactions
Volume59
Issue numberC
DOIs
StatePublished - 1986

Keywords

  • 1-Hydroxy-2-chloroethyl derivatives
  • BSTFA
  • CAA
  • CEO
  • Chloroacetaldehyde
  • Chloroethylene oxide
  • Deoxycytidine adducts
  • GC-MS
  • Gas chromatography-mass spectrometry
  • H-NMR
  • N,O-bis(trimethylsilyl)trifluoroacetamide
  • N-2-Chlorovinyl cytosine
  • RT
  • TMS
  • chloroacetaldehyde
  • chloroethylene oxide
  • gas chromatography-mass spectrometry
  • molecular ion
  • proton nuclear magnetic resonance spectroscopy
  • retention temperature
  • trimethylsilyl

ASJC Scopus subject areas

  • Toxicology

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