title: Crystal Structures, X-Ray Photoelectron Spectroscopy, Thermodynamic Stabilities, and Improved Solubilities of 2-Hydrochloride Salts of Vortioxetine.
abstract: Two vortioxetine (VOT) salts with hydrochloride (VOT-HCl and VOT-0.5HCl) were prepared and structurally characterized. VOT-HCl features 1-dimensional P/M helical chains through N-H···Cl hydrogen bond interactions, whereas VOT-0.5HCl possesses a 1-dimensional zigzag structure in which 2 VOT molecules share a single proton through N···H+···N interactions. VOT-HCl converts into the monohydrate VOT-HCl·H2O after dissolution in water, whereas VOT-0.5HCl remains stable. The N 1s X-ray photoelectron spectroscopy analysis shows a characteristic binding energy peak at approximately 398.0 eV for VOT. The shift to high energy occurs at 400.3 eV for VOT-HCl and VOT-HBr, and at 399.7 eV for VOT-0.5HCl, which supports the salt formation by the degree of proton transfer and is confirmed by single-crystal X-ray analyses. The apparent equilibrium solubilities of VOT in water are significantly improved to 2.90 mg/mL (approximately a 32.0-fold increase over that of the free base) for VOT-HCl and to 0.59 mg/mL (approximately a 5.7-fold increase over that of the free base) for VOT-0.5HCl at 25°C.
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, P. R. China.
authors.forename: Li-Yang
authors.initials: LY
authors.lastname: Li
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, P. R. China.
authors.forename: Sai-Fei
authors.initials: SF
authors.lastname: He
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, P. R. China. Electronic address: lishan@scut.edu.cn.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, ITODYS, UMR 7086 CNRS, 15 rue J-A de Baïf, 75205 Paris Cedex 13, France.
authors.forename: Chang-Zhi
authors.initials: CZ
authors.lastname: Dong
authors.affiliation: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D003460:Crystallization / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D006851:Hydrochloric Acid / Q000032:analysis / Q000737:chemistry*; D056951:Photoelectron Spectroscopy / Q000379:methods*; D010879:Piperazines / Q000032:analysis* / Q000737:chemistry* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D013440:Sulfides / Q000032:analysis* / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics; D000078784:Vortioxetine; D014961:X-Ray Diffraction / Q000379:methods*
chemical_list: D006851:Hydrochloric Acid; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D013440:Sulfides; D000078784:Vortioxetine
keywords: X-ray photoelectron spectroscopy; crystal structure; equilibrium solubility; intrinsic dissolution rate; thermal stability; vortioxetine