Conformational diversity of anthracycline anticancer antibiotics: A density functional theory calculation

The conformational diversity of doxorubicin, daunorubicin, epirubicin, and idarubicin, is studied based on density functional theory calculations at the B3LYP/6-31G(d,p) level of theory. The calculations identified three conformational domains: the anthracycline quinone-hydroquinone backbone, the anchor, and the daunosamine. The backbone exists in three conformations and three prototropic tautomerizations, the anchor in four conformations relating to the orientations of the C8 and C9 atoms, and the daunosamine also in four conformations according to the distance between the amino nitrogen and the quinone oxygen. The overall molecular conformation is determined by combination of the conformational types of all the three conformational domains. Finally, conformations of intercalated drug molecules reported in the literatures are classified according to these criteria.