Binol quinone methides as bisalkylating and DNA cross-linking agents.
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.
Richter
Sara N
SN
Dipartimento di Chimica Organica, Università di Pavia, Via le Taramelli 10, 27100 Pavia, Italy.
Maggi
Stefano
S
Mels
Stefano Colloredo
SC
Palumbo
Manlio
M
Freccero
Mauro
M
D000477:Alkylating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D045563:Indolequinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D009284:Naphthols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010777:Photochemistry; D010782:Photolysis
D000477:Alkylating Agents; C406944:BINOL, naphthol; D003432:Cross-Linking Reagents; D045563:Indolequinones; D009284:Naphthols; C068040:quinone methide; D004247:DNA