Subject: Basic medicine
Subject: Chemical engineering
Subject: Chemical sciences
Subject: Materials engineering
Subject: Medical engineering
Subject: Nano-technology
Subject: Physical sciences
Year: 2023
Type: Article
Type: PeerReviewed
Title: Polymorphism in S(+)Clopidogrel-Picrate: Insights from X-ray Diffraction, Vibrational Spectroscopy, Thermal Analysis, and Quantum Chemistry
Author: Cvetkovski, Aleksandar
Author: Makreski, Petre
Author: Pejov, Ljupco
Author: Stojanovska Pecova, Monika
Author: Bertolasi, Valerio
Author: Gilli, Paola
Author: MacGullivray, Leonard
Abstract: The crystal structures of two pseudopolymorphic forms of S(+)clopidogrel–picrate are reported. Form 1 crystallizes in the monoclinic space group P21 with an ionic couple S(+)ClopH+·Pic− and a molecule of solvent ethanol in the asymmetric unit, while Form 2 crystallizes in the monoclinic space group C2 with two ionic couples in the asymmetric unit. The configurations and conformations of the ionic couples, held together by ionized +N-H···O hydrogen bonds, are nearly identical in the structures. The self-assembly properties are compared with reported clopidogrel salts, including those used in pharmaceutical formulations. The hydrogen bonds are discussed in reference to the general corresponding behavior of the N-bases picrates and the properties of the acid-base coformers. The preparations of the pseudopolymorphs were optimized toward two different methods: solvent evaporation and mechanochemical treatment. Reproducibility to generate the single crystalline phases was confirmed by thermal and vibrational spectroscopic properties. Periodic third-order density-functional tight binding (DFTB3) calculations predict rather small energy difference between the two pure phases of polymorphs 1 and 2. However, the included solvent molecules in Form 1 decrease the lattice energy for ~10.5 kcal mol−1, which leads to a lower ΔElatt. lattice energy in comparison to Form 2 (by ~7.3 kcal mol−1). All predicted trends are in line with the experimentally observed formation of Form 1 instead of its simulated non-solvated Form 1.
Publisher: MDPI
Relation: https://eprints.ugd.edu.mk/36275/
Identifier: oai:eprints.ugd.edu.mk:36275
Identifier: https://eprints.ugd.edu.mk/36275/1/crystals-14-00010-with-cover.pdfIdentifier: Cvetkovski, Aleksandar and Makreski, Petre and Pejov, Ljupco and Stojanovska Pecova, Monika and Bertolasi, Valerio and Gilli, Paola and MacGullivray, Leonard (2023) Polymorphism in S(+)Clopidogrel-Picrate: Insights from X-ray Diffraction, Vibrational Spectroscopy, Thermal Analysis, and Quantum Chemistry. Crystals, 14 (1(10)). ISSN 2073-4352
Identifier: https://doi.org/10.3390/cryst14010010
