Nuclear Magnetic Resonance Study of the Interaction of Phenyldichloroarsine with Calf Thymus DNA

摘要

The vesicant phenyldichloroarsine (PDA) is a lewisite analog and is extremely cytotoxic. Like other trivalent organic arsenicals, its toxicity is presumed to be the result of its reactivity towards essential sulfhydryl groups, especially those of enzymes within cells. Our recent work indicates that erythrocytes absorb PDA because of its reversible reaction with internal glutathione to form a 1:2 adduct. Because of the detrimental environmental and toxicological effects that organic arsenicals such as PDA may impose, we investigated the interactions of PDA with calf thymus DNA fragments, using natural abundance 13C-NMR spectroscopy. Our results indicate the PDA (in aqueous solution phenylarsonous acid, PAA, is the most likely form of the arsenical present but we choose to use the latter nomenclature throughout) binds to DNA in the major groove. The hydrogen-bonded imino protons are not affected. The interaction appears to be selective because no interaction was observed between PDA and t-RNA, and between phenol and DNA. (aw)