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

• Grant number: 16/08823-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 01, 2016
• End date: October 31, 2017
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Javier Alcides Ellena
• Grantee: Juan Carlos Tenorio Clavijo
• Supervisor: Christian W. Lehmann
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Institution abroad: Max Planck Society, Mulheim, Germany
• Associated to the scholarship: 13/07581-9 - Design, Synthesis and Characterization of New Solid Forms of Anti-HIV Drugs., BP.DR

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.

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE BRITO, A. C. F.; CORREA, R. S.; PINTO, A. A.; MATOS, M. J. S.; TENORIO, J. C.; TAYLOR, J. G.; CAZATI, T.. Synthesis, crystal structure, photophysical properties and theoretical studies of a novel bis(phenylisoxazolyl) benzene derivative. Journal of Molecular Structure, v. 1163, p. 197-204, JUL 5 2018. (16/08823-4)

ALBUINI-OLIVEIRA, NATHALIA M.; RUBINGER, MAYURA M. M.; GUILARDI, SILVANA; SOUZA, RAFAEL A. C.; ELLENA, JAVIER; ALVAREZ, NATALIA; TAVARES, EDER C.; ZACCHI, CARLOS H. C.; VIDIGAL, ANTONIO E. C.; LIMA, MARCELO S.; et al. New allyldithiocarbimate salts: Synthesis, structure and antifungal activity. Journal of Molecular Structure, v. 1214, AUG 15 2020. (16/08823-4)

NIQUINI, FABIANO M.; TENORIO, JUAN C.; DA SILVA, MARIA F. G. F.; RIBEIRO, ALAN B.; WANDERLEY, ADILSON; ELLENA, JAVIER; CORREA, RODRIGO S.. On the conformation, molecular interactions and electron density of a natural flavonoid derivative. Journal of Molecular Structure, v. 1220, NOV 15 2020. (13/07581-9, 16/08823-4)

WANDERLEY, A. B.; TENORIO, J. C.; CAMPS, I.; LEHMANN, C. W.; ELLENA, J.. Three-Dimensional topological analysis of the experimental and theoretical electron density of a 5-Fluorocytosine/Isoniazid cocrystal. ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES, v. 77, p. 1-pg., 2021-08-01. (16/08823-4)

CARVALHO, JR., PAULO S.; DINIZ, LUAN F.; TENORIO, JUAN C.; SOUZA, MATHEUS S.; FRANCO, CHRIS H. J.; RIAL, RAFAEL C.; WARSZAWSKI DE OLIVEIRA, KARLA REGINA; NAZARIO, CARLOS E. D.; ELLENA, JAVIER. Pharmaceutical paroxetine-based organic salts of carboxylic acids with optimized properties: the identification and characterization of potential novel API solid forms. CrystEngComm, v. 21, n. 24, p. 3668-3678, JUN 28 2019. (16/08823-4, 12/05616-7, 15/25694-0)

PAIXAO, DRIELLY A.; DE OLIVEIRA, BARBARA C. A.; ALMEIDA, JANAINA DO COUTO; SOUSA, LUANA M.; LOPES, CARLA D.; CARNEIRO, ZUMIRA A.; TEZUKA, DAIANE Y.; CLAVIJO, JUAN CARLOS T.; ELLENA, JAVIER; POLLONI, LORENA; et al. Crystal structure, anti-Trypanosoma cruzi and cytotoxic activities of Cu(II) complexes bearing beta-diketone and alpha-diimine ligands. Inorganica Chimica Acta, v. 499, JAN 2020. (16/08823-4)