Cocrystallization of donepezil and its chloride salt with perfluorated halogen bond donors

U sklopu ovog diplomskog rada izučavana je mogućnost priprave kokristala farmaceutski aktivne tvari, donepezila i njegove kloridne soli, s odabranim perfluoriranim donorima halogenske veze različite topičnosti i geometrije: jodpentafluorbenzenom, dijod-1,2-tetraflu-orbenzenom, dijod-1,3-tetrafluorbenzenom, dijod-1,4-tetraflurobenzenom i trijod-1,3,5-triflurobenzenom. Sa stajališta kristalnog inženjerstva, navedene molekule zanimljive su zbog prisutnosti funkcijskih skupina koje su potencijalni akceptori i donori halogenskih ili vodikovih veza. Mehanokemijskom sintezom i konvencionalnim sintezama iz otopine pripravljena su tri nova kokristala i jedan solvat kokristala soli. Dobiveni produkti okarakterizirani su difrakcijom rentgenskog zračenja u polikristalnom uzorku i jediničnom kristalu, metodama termičke analize te pretražne elektronske mikroskopije. Prema rezultatima strukturne analize utvrđeno je da su dominantne međumolekulske interakcije u priređenim kokristalima halogenske veze I∙∙∙N i I∙∙∙O, gdje su akceptorski atomi halogenskih veza piperidilni dušikov i karbonilni kisikov atom.Within this diploma thesis, an active pharmaceutical ingredient, donepezil, and its chloride salt have been studied in cocrystallization experiments with selected perfluorinated halogen bond donors of different topicity and geometry: iodopentafluorobenzene, 1,2-diiodotetrafluorobenzene, 1,3-diiodotetrafluorobenzene, 1,4-diiodotetrafluorobenzene and 1,3,5-triiodotrifluorobenzene. From a crystal engineering standpoint, the compounds are interesting due to the presence of various potential halogen and hydrogen bond donor and acceptor species. Mechanochemical synthesis and conventional solution-based crystallization experiments resulted in three new cocrystals and one cocrystal salt solvate. The obtained products were characterized by powder X-ray diffraction and single crystal X-ray diffraction, by thermal methods and scanning electron microscopy. The structural analysis of the cocrystals reveals that the dominant supramolecular interactions are halogen bonds I∙∙∙N and I∙∙∙O, where acceptor atoms of halogen bonds are piperidinyl nitrogen and carbonyl oxygen atoms