title: Supramolecular synthesis based on piperidone derivatives and pharmaceutically acceptable co-formers.
abstract: The target complexes, bis{(E,E)-3,5-bis[4-(diethylamino)benzylidene]-4-oxopiperidinium} butanedioate, 2C27H36N3O(+)·C4H4O4(2-), (II), and bis{(E,E)-3,5-bis[4-(diethylamino)benzylidene]-4-oxopiperidinium} decanedioate, 2C27H36N3O(+)·C10H16O4(2-), (III), were obtained by solvent-mediated crystallization of the active pharmaceutical ingredient (API) (E,E)-3,5-bis[4-(diethylamino)benzylidene]-4-piperidone and pharmaceutically acceptable dicarboxylic (succinic and sebacic) acids from ethanol solution. They have been characterized by melting point, IR spectroscopy and single-crystal X-ray diffraction. For the sake of comparison, the structure of the starting API, (E,E)-3,5-bis[4-(diethylamino)benzylidene]-4-piperidone methanol monosolvate, C27H35N3O·CH4O, (I), has also been studied. Compounds (II) and (III) represent salts containing H-shaped centrosymmetric hydrogen-bonded synthons, which are built from two parallel piperidinium cations and a bridging dicarboxylate dianion. In both (II) and (III), the dicarboxylate dianion resides on an inversion centre. The two cations and dianion within the H-shaped synthon are linked by two strong intermolecular N(+)-H···(-)OOC hydrogen bonds. The crystal structure of (II) includes two crystallographically independent formula units, A and B. The cation geometries of units A and B are different. The main N-C6H4-C=C-C(=O)-C=C-C6H4-N backbone of cation A has a C-shaped conformation, while that of cation B adopts an S-shaped conformation. The same main backbone of the cation in (III) is practically planar. In the crystal structures of both (II) and (III), intermolecular N(+)-H···O=C hydrogen bonds between different H-shaped synthons further consolidate the crystal packing, forming columns in the [100] and [101] directions, respectively. Salts (II) and (III) possess increased aqueous solubility compared with the original API and thus enhance the bioavailability of the API.
authors.affiliation: Department of Chemistry and Biology, New Mexico Highlands University, 803 University Avenue, Las Vegas, NM 87701, USA.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Sandhu
authors.forename: Sergiu
authors.initials: S
authors.lastname: Draguta
authors.forename: Tiffany L
authors.initials: TL
authors.lastname: Kinnibrugh
authors.forename: Victor N
authors.initials: VN
authors.lastname: Khrustalev
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Timofeeva
mesh_terms: D002412:Cations / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005021:Ethylamines / Q000737:chemistry*; D006860:Hydrogen Bonding; D008968:Molecular Conformation; D015394:Molecular Structure; D010881:Piperidones / Q000737:chemistry*; D012492:Salts / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D014867:Water
chemical_list: C581605:(E,E)-3,5-bis(4-(diethylamino)benzylidene)-4-piperidone; D002412:Cations; D005021:Ethylamines; D010881:Piperidones; D012492:Salts; D012997:Solvents; D014867:Water