title: A complementary experimental and computational study of loxapine succinate and its monohydrate.
abstract: The crystal structures of loxapine succinate [systematic name: 4-(2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-1-ium 3-carboxypropanoate], C18H19ClN3O(+)·C4H5O4(-), and loxapine succinate monohydrate {systematic name: bis[4-(2-chlorodibenzo[b,f][1,4]oxazepin-11-yl)-1-methylpiperazin-1-ium] succinate succinic acid dihydrate}, 2C18H19ClN3O(+)·C4H4O4(2-)·C4H6O4·2H2O, have been determined using X-ray powder diffraction and single-crystal X-ray diffraction, respectively. Fixed cell geometry optimization calculations using density functional theory confirmed that the global optimum powder diffraction derived structure also matches an energy minimum structure. The energy calculations proved to be an effective tool in locating the positions of the H atoms reliably and verifying the salt configuration of the structure determined from powder data. Crystal packing analysis of these structures revealed that the loxapine succinate structure is based on chains of protonated loxapine molecules while the monohydrate contains dispersion stabilized centrosymmetric dimers. Incorporation of water molecules within the crystal lattice significantly alters the molecular packing and protonation state of the succinic acid.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, Scotland.
authors.forename: Rajni M
authors.initials: RM
authors.lastname: Bhardwaj
authors.forename: Blair F
authors.initials: BF
authors.lastname: Johnston
authors.forename: Iain D H
authors.initials: ID
authors.lastname: Oswald
authors.forename: Alastair J
authors.initials: AJ
authors.lastname: Florence
mesh_terms: D039301:Computers, Molecular; D008152:Loxapine / Q000737:chemistry*; D015394:Molecular Structure; D033362:Powder Diffraction; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D014867:Water; D008152:Loxapine
keywords: CASTEP; crystal structure determination; geometry optimization; loxapine succinate; powder X-ray diffraction; single-crystal diffraction