title: Polycyclic ferrocenyl(dihydro)thiazepine derivatives: Diastereo-selective synthesis, characterization, electrochemical behavior, theoretical and biological investigation.
abstract: The reaction of E-2-ferrocenylmethylidenetetralones and E,E-2,6-bis-(ferrocenylmethylidene)-cyclohexanone with 2-aminothiophenol proceed with high diastereoselectivity, forming the ~4.5:1 mixture of trans- and cis-isomers of polycyclic ferrocenylthiazepines, respectively. The reactions of E,E-2,5-bis-(ferrocenylmethylidene)cyclopentanone and E,E-3,5-bis-(ferrocenylmethylidene)-1-methyl-4-piperidone with 2-aminothiophenol take place stereo specifically to form the diastereomeric tricyclic thiazepines of cis- and trans-configuration, respectively. The structures of the obtained compounds were established by IR,1H and13C NMR spectroscopy and mass-spectrometry. The structures of the trans-tetralino[1,2a]-, trans-5,7-dimethyltetralino[1,2a]-2-ferrocenyl [1,5]benzo-2,3-dihydrothiazepines and cis-5-ferrocenyl-methylidenecyclopentano[1,2a]-2-ferrocenyl- [1,5]benzo-2,3-dihydrothiazepine were confirmed by X-ray diffraction analysis. An electrochemical study reveals that the diferrocenyl derivatives belong to a Class I compounds of the Robin-Day classification. This behavior is explained by the analysis of frontier orbitals as calculated by density functional theory, showing that only one ferrocenyl unit participates in the generation of HOMO and LUMO orbitals. Compounds 4a and 4c showed similar capacity to inhibit the proliferation of HM1: IMSS trophozoite cultures than the first choice drug for human amoebiasis treatment, metronidazole. Morphological changes induced in the trophozoites after drug exposure suggest a redox in balance as the probable mechanism of the parasite death.
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, CD.MX, 04510, Mexico.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Sánchez García
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, CD.MX, 04510, Mexico.
authors.forename: Yanis
authors.initials: Y
authors.lastname: Toledano-Magaña
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, CD.MX, 04510, Mexico.
authors.forename: Marcos
authors.initials: M
authors.lastname: Flores-Alamo
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, CD.MX, 04510, Mexico.
authors.forename: Elena
authors.initials: E
authors.lastname: Martínez-Klimova
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Utah, UT 84112, USA.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Galindo-Murillo
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, CD.MX, 04510, Mexico.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Hernández-Ayala
authors.affiliation: Departamento de Electroquímica, Centro de Investigación y Desarrollo Tecnológico en Electroquímica, S.C., Querétaro, 76703, Mexico.
authors.forename: Luis
authors.initials: L
authors.lastname: Ortiz-Frade
authors.affiliation: Departamento de Fisicoquímica, Instituto de Química, Universidad Nacional Autónoma de México, CD. MX, 04510, Mexico. Electronic address: jcgr@iquimica.unam.mx.
authors.forename: Juan C
authors.initials: JC
authors.lastname: García-Ramos
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, CD.MX, 04510, Mexico. Electronic address: klimova@unam.mx.
authors.forename: Elena I
authors.initials: EI
authors.lastname: Klimova
mesh_terms: D000562:Amebiasis / Q000188:drug therapy*; D000563:Amebicides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004748:Entamoeba histolytica / Q000378:metabolism*; D005296:Ferrous Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D011083:Polycyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013841:Thiazepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D053058:Trophozoites / Q000378:metabolism
chemical_list: D000563:Amebicides; D005296:Ferrous Compounds; D011083:Polycyclic Compounds; D013841:Thiazepines
keywords: Amoebicidal activity; DFT; Electrochemistry; Ferrocene; Tetracyclic mono-ferrocenylthiazepines; Tricyclic diferrocenylthiazepines; X-ray structural analysis