Electron Density Studies of Antiretroviral Drugs as a tool for the Design of New Solid Phases.

Abstract

This research proposal aims the development of theoretical and experimental Charge Density (CD) studies of new solid forms of antiretroviral drugs, initially of the lamivudine (3TC), one of the most marketed and effective anti-HIV and anti-hepatitis-B drug. The different solid forms derivatives of the lamivudine and other anti-HIV drugs have been obtaining through crystal engineering approach, using co-formers that are approved to use in drug formulations as established by the Generally Recognized As Safe (GRAS) list deferred by the Food and Drug Administration (FDA) agency. The many successfully outcomes obtained by this methodology, encourage us to study the CD distribution of these solid forms in detail once we can to explain: the reactivity of the drugs, the molecular topology and even the pharmaceutical performance, owing the drug-receptors interaction features that involve the recognition of the electronic structure of the drug, which can be evaluated by the information of the Multipolar Model (MM) and the quantum theory of Atom In Molecules (AIM) into the formalism of Bader Analysis. In this way, we propose to carry out high-resolution X-ray diffraction experiments that will allow us to construct Multipolar Models, through the Hansen-Coppens formalism and to get the CD deformation of the different lamiduvine solid forms, as well as other topologic molecular properties. Meanwhile, theoretical studies at isolated and periodical conditions will allow to complement and to follow up the electronic properties of these systems.