The anticancer drug-DNA complex: Femtosecond primary dynamics for anthracycline antibiotics function

The anthracycline-DNA complex, which is a potent agent for cancer chemother apy, has a unique intercalating molecular structure with preference to the GC bases of DNA, as shown by Rich's group in studies of single-crystal x-ra y diffraction. Understanding cytotoxicity and its photoenhancement requires the unraveling of the dynamics under the solution-phase, physiological con dition. Here we report our first study of the primary processes of drug fun ction. In a series of experiments involving the drug (daunomycin and adriam ycin) in water, the drug-DNA complexes, the complexes with the four nucleot ides (dGTP, dATP, dCTP, and dTTP), and the drug-apo riboflavin-binding prot ein, we show the direct involvement of molecular oxygen and DNA base-drug c harge-separation-the rates for the reduction of the drug and dioxygen indic ate the crucial role of drug/base/O-2 in the efficient and catalytic redox cycling. These dynamical steps, and the subsequent reactions of the superox ide product(s), can account for the photoenhanced function of the drug in c ells, and potentially for the cell death.