Interplay of Hydrogen Abstraction and Radical Repair in the Generation of Single- and Double-Strand DNA Damage by the Esperamicins

The source of hydrogens for the quenching of the phenylene diradical produced by esperamicin A (espA) and by esperamicin C (espC) in the presence of specifically deuteriated, double-stranded DNA (dsDNA) has been determined. Remarkably, both espA and espC were quenched at both positions of the diphenylene radical by exclusive abstraction of hydrogen from dsDNA. EspC, a predominantly ds-cleaver, afforded results consistent with 4‘- and 5‘-hydrogen transfer. EspA, a predominantly ss-cleaver, revealed no 4‘-hydrogen transfer; however, results were consistent with 5‘-hydrogen transfer and with the recently proposed 1‘-hydrogen transfer (Yu, L.; Golik, J.; Harrison, R.; Dedon, P. J. Am. Chem. Soc. 1994, 116, 9733−9738). For espA, insufficient double strand DNA damage was produced to account for the role of DNA as the exclusive hydrogen source. In order to resolve this discrepancy, several reductants were used to activate espA and espC. The results indicated that a substantial portion of radical lesions produced...