Changing Selectivity of DNA Oxidation from Deoxyribose to Guanine by Ligand Design and a New Binuclear Copper Complex

• Published in: Journal of the American Chemical Society Vol. 127; no. 2; pp. 520 - 521
• Main Authors: Li, Lei, Karlin, Kenneth D, Rokita, Steven E
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 19.01.2005
• Subjects: Biological and medical sciences; Copper - chemistry; Deoxyribose - chemistry; Deoxyribose - metabolism; DNA, Single-Stranded - chemistry; DNA, Single-Stranded - metabolism; Fundamental and applied biological sciences. Psychology; Guanine - chemistry; Ligands; Mechanisms. Catalysis. Electron transfer. Models; Molecular biophysics; Nucleic Acid Conformation; Oligonucleotides - chemistry; Oxidation-Reduction; Physical chemistry in biology; Cationic complex; Ligand effect; Chemical modification; Chemoselectivity; Gel electrophoresis; Oxidative degradation; Dinuclear complex; Copper Complexes; Nucleic acid
• DOI: 10.1021/ja044209e
• ISSN: 0002-7863

A dinuclear copper complex [CuII 2(PD‘O)(H2O)2]3+ (1) (where PD‘OH is a pyridylalkylamine containing binucleating ligand) promotes guanine oxidation in single-stranded DNA in the presence of 3-mercaptopropionic acid and dioxygen. This reaction is detected after subsequent piperidine treatment. Little spontaneous strand scission indicative of deoxyribose oxidation is observed in contrast to the results known for other copper complexes. Chemical characterization and nanospray ionization mass spectrometry analysis of oligodeoxynucleotides treated with 1 suggest conversion of guanine residues to their 2,6-diamino-5-formamidino-4-hydroxypyrimidine (+18 amu) and possibly 5,8-dihydroxy-7,8-dihydroguanine (+34 amu) derivatives. The selectivity toward nucleobase rather than deoxyribose oxidation is discussed in terms of the specific nature of the dicopper (hydro)peroxo species formed with the PD‘OH ligand versus the intermediates formed in the presence of other binucleating ligands.