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Presentations including 'Three-Dimensional topological analysis of the experimenta'

Poster - 21 Quantum: Quantum crystallography
Time: 17/Aug/2021: 4:40pm-5:40pm

ID: 402 / Poster - 21 Quantum: 9
All topics
Oral/poster
MS: Quantum crystallography in materials science, Quantum crystallography research, Polymorphism and structural transformation of organic crystals from synthesis to characterization, Quantum crystallographic studies on intra/inter-molecular interactions, New trends in pharmaceutical materials, Non-covalent interactions in crystal engineering
Keywords: electronic charge density; drug-drug cocrystals; multipolar refinement; atom in molecules; topology

Three-Dimensional topological analysis of the experimental and theoretical electron density of a 5-Fluorocytosine/Isoniazid cocrystal

Adilson Barros Wanderley1, Juan Carlos Tenorio2, Ihosvany Camps3, Christian W. Lehmann4, Javier Ellena1

1Instituto de Física de São Carlos - USP, C.P. 369, 13560-970, São Carlos, SP, Brazil,; 2Instituto de Química, Universidade Estadual de Campinas - Unicamp, CEP 13083-970, Campinas, SP, Brazil; 3Departamento de Física, ICEx/UNIFAL-MG, Alfenas, MG, 37133-840, Brazil,; 4Max-Planck-Institut für Kohlenforschung, 45470, Mülheim a.d Ruhr, Germany.

Drug-drug cocrystals involve the combination of two or more active pharmaceutical ingredients (API) with their original chemical characteristics maintained without breaking or forming new covalent bonds, thus ensuring its effectiveness.[1] Its pharmaceutical properties are determined by the polarity of functional groups, the electrostatic potential and the available intermolecular interactions, which in turn are characterized by the three-dimensional crystalline arrangement and governed by its molecular electronic structure.[2] These molecular electron properties and their relationships with the charge density topology can be analysed by experimental and theoretical studies.

In this manner, the experimental charge density analysis of the pharmaceutical drug-drug cocrystal involving the antimetabolite prodrug 5-Fluorocytosine (5-FC) and the tuberculostatic drug Isoniazid (INH), named 5FC-INH, [3] has been carried out based on the Hansen & Coppens aspherical multipolar model refinement,[4] using high resolution X-ray diffraction data at low temperature ((sin(θmax)/λ=1.15 Å-1, 150K). The experimental model was compared with those derived from corresponding theoretical calculations for solid-state and gas-phase conditions using density functional theory (DFT) methods at the B3LYP6-311++G** level of theory.[5] The detailed study of the molecular electron density, its corresponding topology and charge distribution were based on the quantum theory of atom in molecules (QTAIM).[6] The charge density distribution and analysis of topological properties revealed that the C—F bond may have a transit closed-shell configuration (Fig. 1). This analysis also allowed to verify the charge delocalization due to resonance-assisted hydrogen bond (RAHB) in the formation of the heterosynthon that stabilizes the crystal packing.[7]

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