Combined crystallographic and computational investigation of the solvent disorder present in a new tipiracil hydrochloride methanol solvate–hydrate. Issue 18 (8th April 2022)

• Record Type: Journal Article
• Authors: Barbas, Rafael; Font-Bardia, Mercè; de Sande, Dafne; Frontera, Antonio; Prohens, Rafel
• Is Part Of: CrystEngComm. Volume 24:Issue 18(2022)
• Page Start: 3347
• Page End: 3354
• Publication Date: 2022-04-08
• Subjects: Crystals -- Periodicals; Crystal growth -- Periodicals; Crystallography -- Periodicals; Cristaux -- Périodiques; Cristaux -- Croissance -- Périodiques; Cristallographie -- Périodiques; 548
• DOI: 10.1039/d2ce00161f
• Languages: English
• ISSNs: 1466-8033

Abstract

Abstract : We report a computational and crystallographic analysis of tipiracil hydrochloride (methanol solvate–hydrate). It shows a complex network of H-bonds with static discrete disorder in two out of the three symmetry-independent solvent molecules. Abstract : This work reports a combined computational and experimental analysis of the crystal structure of the cancer drug tipiracil hydrochloride in the form of a methanol solvate–hydrate (4 : 1 : 3, molar ratio). The crystal structure shows a complex network of H-bonds with static discrete disorder in two out of the three symmetry-independent solvent molecules, which has been studied by means of DVS and TGA techniques. MEP surface calculations shows a region of positive potential (σ-hole) along the C–Cl bond, which induces the formation of Cl⋯O contacts that are relevant in the crystal packing. The hydrogen and halogen bonding assemblies were further analyzed using density functional theory (DFT), the quantum theory of "atom-in-molecules" (QTAIM) and the noncovalent interaction plot (NCIplot).