Molecular electrostatic potential maps of the anti-cancer drugs daunomycin and adriamycin: an ab initio theoretical study

Abstract

Molecular geometries of the anti-cancer drug molecules adriamycin and daunomycin were optimized using the restricted Hartree–Fock procedure and the 6-31G and 6-31G* basis sets. Molecular electrostatic potentials (MEP) were obtained on the van der Waals surfaces of the molecules using the MEP-derived CHelpG point charges. MEP minima and MEP surfaces corresponding to chosen MEP values were obtained using the continuous electron density distributions at the SCF level. Hydrogen bonding interactions involving the drug molecules, DNA and the surrounding environment suggested in experimental studies earlier are mostly supported by the present MEP values. However, this study also reveals additional useful information in the sense that the calculated MEP values near the different atoms vary over a wide range indicating that the hydrogen bond strengths involving them would also vary appreciably. Occurrence of a strong binding of a Na + ion to both O 4 and O 5 is indicated by the present MEP patterns. Further, the role of the binding of an oxygen atom that is present in adriamycin but not in daunomycin and is associated with a large negative MEP value with DNA appears to be very important due to which the former drug is more effective as an anti-cancer agent than the latter.