Binol quinone methides as bisalkylating and DNA cross-linking agents

J Am Chem Soc. 2004 Nov 3;126(43):13973-9. doi: 10.1021/ja047655a.

Abstract

The photogeneration and detection of new binol quinone methides undergoing mono- and bisalkylation of free nucleophiles was investigated by product distribution analysis and laser flash photolysis in water solution using binol quaternary ammonium derivatives 2 and 12 as photoactivated precursors. The alkylation processes of N and S nucleophiles are strongly competitive with the hydration reaction. DNA cross-linking potency of the water-soluble binol quaternary ammonium salt 2 was investigated as a pH function and compared to that of other quaternary ammonium salts capable of benzo-QM (QM = quinone methide) photogeneration by gel electrophoresis. DFT calculations in the gas phase and in water bulk on the binol and benzo quaternary ammonium salts 2 and 4 evidence structural and electrostatic features of the binol derivative which might offer a rationalization of its promising high photo-cross-linking efficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / chemical synthesis
  • Alkylating Agents / chemistry*
  • Alkylating Agents / pharmacology
  • Cross-Linking Reagents / chemical synthesis
  • Cross-Linking Reagents / chemistry*
  • Cross-Linking Reagents / pharmacology
  • DNA / chemistry
  • DNA / drug effects*
  • Indolequinones / chemical synthesis
  • Indolequinones / chemistry*
  • Indolequinones / pharmacology
  • Models, Molecular
  • Molecular Conformation
  • Naphthols / chemical synthesis
  • Naphthols / chemistry*
  • Naphthols / pharmacology
  • Photochemistry
  • Photolysis

Substances

  • Alkylating Agents
  • BINOL, naphthol
  • Cross-Linking Reagents
  • Indolequinones
  • Naphthols
  • quinone methide
  • DNA