ELECTRONIC STRUCTURE AND PARTIAL CHARGE DISTRIBUTION OF DOXORUBICIN UNDER DIFFERENT MOLECULAR ENVIRONMENTS A THESIS IN Physics

Doxorubicin (trade name Adriamycin, abbreviated DOX) is a well-known anthracyclic chemotherapeutic used in treating a variety of cancers including acute leukemia, lymphoma, multiple myeloma, and a range of stomach, lung, bladder, bone, breast, and ovarian cancers. The purpose of the present work is to study electronic structure, partial charge distribution and interaction energy of DOX under different environments. It provides a framework for better understanding of bioactivity of DOX with DNA. While in this work, we focus on DOX−DNA interactions; the obtained knowledge could be translated to other drug−target interactions or biomolecular interactions. The electronic structure and partial charge distribution of DOX in three different molecular environments: isolated, solvated, and intercalated into a DNA complex, were studied by first principles density functional methods. It is shown that the addition of solvating water molecules to DOX and the proximity and interaction with DNA has a significant impact on the electronic structure as well as the partial charge distribution. The calculated total partial charges for DOX in the three models are 0.0, +0.123 and -0.06 electrons for the isolated, solvated, and intercalated state, respectively. Furthermore, by using the more accurate ab initio partial charge values