PULSE-RADIOLYSIS STUDIES OF ELECTRON MIGRATION IN DNA FROM DNA BASE-RADICAL ANIONS TO NITROACRIDINE INTERCALATORS IN AQUEOUS-SOLUTION

The reactions of the aquated electron (e(aq)-) with intercalators of high reduction potential (nitracrine and related basic nitroacridines) has been investigated by pulse radiolysis in the presence of DNA in aqueous solution. Under conditions where the majority of the e(aq)- species react initially with DNA bases (high DNA : drug ratios) a slower subsequent electron transfer to the intercalator was observed. The rate of this intra-complex transfer, expressed as DNA base pairs traversed per second, was in the range (1.2-3.1) x 10(5) base pairs s-1 and increased in order of the one-electron reduction potentials of the DNA-bound intercalators. No transfer was seen to the much less electron affinic des-nitro analogue of the nitroacridines. Only a small proportion of the initial DNA base radicals (less-than-or-equal-to 50%) underwent this intra-complex electron transfer. Even for the most efficient electron trap, nitracrine, the apparent mean electron migration distance was only three base pairs. A slow secondary reduction of nitroacridines [(0.08-5.0) x 10(4) base pairs s-1] was also observed with a proportion of the essentially immobile .OH-induced DNA radicals. This secondary reaction may well serve as a measure of the mobility of the DNA-bound intercalators. This study therefore implies a lack of extensive migration of DNA-associated electrons in aqueous solution, although it does not exclude the possibility that more mobile electrons produced by direct ionization of DNA might migrate over large distances.