Combined crystallographic and computational investigation of the solvent disorder present in a new tipiracil hydrochloride methanol solvate-hydrate

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 (sigma-hole) along the C-Cl bond, which induces the formation of ClMIDLINE HORIZONTAL ELLIPSISO 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).