title: Thermal, X-ray Structural, and Dissolution Characteristics of Solid Forms Derived from the Anticancer Agents 2-Methoxyestradiol and 2-Methoxyestradiol-3,17-O,O-Bis-Sulfamate.
abstract: The aim of the study was to generate alternative solid forms of 2-methoxyestradiol (2ME) and its sulfamoylated derivative 2-methoxyestradiol-3,17-O,O-bis-sulfamate (2MES), both of which are potent anticancer agents with no significant history of solid-state investigation. Screening for polymorphs and solvates by a variety of procedures yielded four distinct species: a crystalline form of 2ME, an amorphous form of 2ME, a chloroform solvate 2ME·(CHCl3 )2 , and the hemihydrate of the bis-sulfamate, 2MES·(H2 O)0.5 . Hydrogen-bonded assembly of 2ME molecules into layers in both crystalline 2ME and its chloroform solvate was established using single-crystal X-ray diffraction. This technique also revealed disorder of the sulfamate group at position 17 in both molecules comprising the asymmetric unit in the crystal of 2MES·(H2 O)0.5 . The thermal stabilities of the crystalline phases were recorded using hot-stage microscopy, thermogravimetry, and differential scanning calorimetry, and the results were reconciled with the crystal structures. Aqueous dissolution rates measured at 37°C generally decreased in the order 2MES·(H2 O)0.5 > 2ME(amorphous) > 2ME(crystalline).
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
authors.forename: Mino R
authors.initials: MR
authors.lastname: Caira
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
authors.forename: Susan A
authors.initials: SA
authors.lastname: Bourne
authors.affiliation: Department of Chemistry, University of Cape Town, Rondebosch, Cape Town, 7701, South Africa.
authors.forename: Halima
authors.initials: H
authors.lastname: Samsodien
mesh_terms: D000077584:2-Methoxyestradiol; D018931:Antineoplastic Agents, Hormonal / Q000737:chemistry*; D002725:Chloroform; D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry; D006860:Hydrogen Bonding; D008958:Models, Molecular; D012995:Solubility; D012997:Solvents; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: C500344:2-methoxyestradiol-3,17-bis-O,O-sulfamate; D018931:Antineoplastic Agents, Hormonal; D012997:Solvents; D004958:Estradiol; D000077584:2-Methoxyestradiol; D002725:Chloroform
keywords: 2-methoxyestradiol; 2-methoxyestradiol-3,17-O,O-bis-sulfamate; crystal structure; crystallization; dissolution; hydrates/solvates; polymorphism; thermal analysis