DYNAMICS OF ANTHRACYCLINES/DNA INTERACTION: A LASER TIME‐RESOLVED FLUORESCENCE STUDY*

Abstract

Abstract— The dynamic interaction with DNA of two representative anthracyclines, daunomycin and 5‐iminodaunomycin, differing in the redox properties, DNA affinity and cardiotoxicity, has been characterized by laser time‐resolved fluorescence decay. The free drug fluorescence decay is mono‐exponential for daunomycin in both phosphate and TRIS buffer and becomes biexponential in the case of 5‐iminodaunomycin when the phosphate buffer is used. In the presence of DNA, daunomycin excited with a mode‐locked Ar laser at 364 nm shows a three‐exponential fluorescence decay with time constants T 1 =2.92 ns, T 2 = 1.42 ns, T 3 =0.31 ns. The first lifetime refers to the decay of the excited state of the chromophore bound on the DNA backbone, whereas T 2 and T 3 are assigned to two different conformations of the intercalation complex. An estimate of the molar extinction coefficient and the relative quantum yield of the variously bound drug is made. The 5‐iminodaunomycin fluorescence decay lifetime is less sensitive to the nature of the environment probably because, being a poorer intercalator, it binds more easily on the phosphate backbone and thus the electronic perturbation resulting from the binding is not as strong as in the case of daunomycin.