Abstract
Abstract Fifteen O-benzoyl oxime esters (i.e., 1–15) were synthesized from condensation of para-substituted benzoyl chlorides (p-XC6H4COCl; X = H, Me, NO2, F, CN) with oximes of fluoren-9-one, thioxanthen-9-one 10,10-dioxide, and anthraquinone. Irradiation with UV light (312 nm) of these oxime esters in a phosphate buffer (pH 5.0–8.0) containing the supercoiled circular □X174 RFI DNA (form I; 50 □M/base pair) under aerobic conditions for 2.0 h resulted in the single-strand scission of DNA. Anthraquinone-O-9-(4-cyanobenzoyl)oxime (13) with binding constant of 3.31 104 M–1 exhibited the highest cleaving efficiency among the 15 compounds; the ratio of (form II)/(form I) for 13 was 1.0 at the concentration as low as 10 □M. It also showed the capability for double-strand scission at the concentration as low as 50 □M. Results from control experiments indicate that UV light was essential and functioned as a "trigger" to initiate the DNA cleavage processes. The EPR and trapping techniques were applied to prove the major cleaving species for DNA were para-substituted benzoyloxy radicals, in which the influence resulting from the substituents follows the order H < Me < NO2 < F < CN. The iminyl radical resulting from the homolytic fission of the weak =N–OC(=O) single bond in 13 was responsible in part for the double-strand scission.