A complementary experimental and computational study of loxapine succinate and its monohydrate

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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+center dot 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, 2C(18)H(19)ClN(3)O(+)center dot C4H4O42-center dot C4H6O4 center dot 2H(2)O, 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.
LanguageEnglish
Pages1273-1378
Number of pages6
JournalActa Crystallographica Section C: Crystal Structure Communications
Volume69
Issue number11
DOIs
Publication statusPublished - 1 Nov 2013

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Loxapine
Succinic Acid
Powder Diffraction
X-Ray Diffraction
Names
Molecules
Protonation
Crystal lattices
Dimers
Powders
X ray powder diffraction
Density functional theory
Salts
Crystal structure
Single crystals
X ray diffraction
Atoms
Crystals
Geometry
Water

Keywords

  • CASTEP
  • crystal structure determination
  • geometry optimization
  • loxapine succinate
  • powder X-ray diffraction
  • single-crystal diffraction

Cite this

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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+center dot 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, 2C(18)H(19)ClN(3)O(+)center dot C4H4O42-center dot C4H6O4 center dot 2H(2)O, 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.",
keywords = "CASTEP, crystal structure determination, geometry optimization, loxapine succinate, powder X-ray diffraction, single-crystal diffraction",
author = "Bhardwaj, {Rajni M.} and Johnston, {Blair F.} and Oswald, {Iain D. H.} and Florence, {Alastair J.}",
year = "2013",
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doi = "10.1107/S0108270113029363",
language = "English",
volume = "69",
pages = "1273--1378",
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T1 - A complementary experimental and computational study of loxapine succinate and its monohydrate

AU - Bhardwaj, Rajni M.

AU - Johnston, Blair F.

AU - Oswald, Iain D. H.

AU - Florence, Alastair J.

PY - 2013/11/1

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N2 - 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+center dot 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, 2C(18)H(19)ClN(3)O(+)center dot C4H4O42-center dot C4H6O4 center dot 2H(2)O, 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.

AB - 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+center dot 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, 2C(18)H(19)ClN(3)O(+)center dot C4H4O42-center dot C4H6O4 center dot 2H(2)O, 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.

KW - CASTEP

KW - crystal structure determination

KW - geometry optimization

KW - loxapine succinate

KW - powder X-ray diffraction

KW - single-crystal diffraction

U2 - 10.1107/S0108270113029363

DO - 10.1107/S0108270113029363

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EP - 1378

JO - Acta Crystallographica Section C: Crystal Structure Communications

T2 - Acta Crystallographica Section C: Crystal Structure Communications

JF - Acta Crystallographica Section C: Crystal Structure Communications

SN - 0108-2701

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