Self-association of daunomycin.
Daunomycin, a potent anthracycline antibiotic, self-associates in aqueous solution at concentrations greater than 10 microM. We report here visible absorbance, sedimentation equilibrium, and proton nuclear magnetic resonance (NMR) experiments that characterize this self-association. In contrast to earlier reports that the process is a simple dimerization, we find that an indefinite association model best fits our data, with an intrinsic association constant, Ki, equal to 1500 M-1. From the temperature dependence of the observed NMR spectra, an enthalpy of approximately -8.0 kcal/mol is calculated. The NMR data show that the aromatic protons of the anthracycline portion of the drug are most affected by aggregation, probably due to stacking of the anthracycline rings. Knowledge of the applicable model for the self-association process, and the equilibrium constant that describes the process, enables us to assess quantitatively the possible effects of drug aggregation on the interpretation of drug-DNA binding data. For the ionic conditions most commonly used in such studies, the amount of aggregated daunomycin will be slight and may safely be ignored.
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003630:Daunorubicin; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D013053:Spectrophotometry; D013816:Thermodynamics
D046911:Macromolecular Substances; D003630:Daunorubicin