2-Ferrocenyl-2-[(2-ferrocenylethen-yl)(morpholin-4-yl)meth-yl]-1,3-di-thiol-ane.

The mol-ecular structure of 2-ferrocenyl-2-[(2-ferrocenylethen-yl)(morpholin-4-yl)meth-yl]-1,3-di-thiol-ane, [Fe2(C5H5)2(C19H21NOS2)] or C29H31Fe2NOS2, has the ferrocenyl fragments in a trans disposition with respect to the vinyl group. One of the methyl-ene groups is disordered over two sites with occupancies of 0.782 (13):0.218 (13). In the crystal, cyclo-penta-dienyl-C-H⋯O(morpholin-yl) inter-actions feature within helical chains parallel to the c-axis direction. The chains are connected by methyl-ene- and cyclo-penta-dienyl-C-H⋯O(cyclo-penta-dien-yl) inter-actions.

4,6-Diferrocenyl-5-(morpholin-4-yl)-1,2,3-triazine.

The structure of the title Fe complex, [Fe(C5H5)2(C17H16N4O)], was determined at 130 K, and has ortho-rhom-bic (Pna21) symmetry. It is of inter-est with respect to the class of triazine heterocyclic compounds: the triazine ring is substituted by two ferrocenyl and one morpholine groups. The crystal structure features C-H⋯O and C-H⋯N non-classical hydrogen bonds.

The Amoebicidal Activity of Diferrocenyl Derivatives: A Significant Dependence on the Electronic Environment.

Amoebiasis is the second leading cause of death worldwide associated with parasitic disease and is becoming a critical health problem in low-income countries, urging new treatment alternatives. One of the most promising strategies is enhancing the redox imbalance within these susceptible parasites related to their limited antioxidant defense system. Metal-based drugs represent a perfect option due to their extraordinary capacity to stabilize different oxidation states and adopt diverse geometries, allowing their interaction with several molecular targets. This work describes the amoebicidal activity of five 2-(Z-2,3-diferrocenylvinyl)-4X-4,5-dihydrooxazole derivatives (X = H (3a), Me (3b), iPr (3c), Ph (3d), and benzyl (3e)) on Entamoeba histolytica trophozoites and the physicochemical, experimental, and theoretical properties that can be used to describe the antiproliferative activity. The growth inhibition capacity of these organometallic compounds is strongly related to a fine balance between the compounds' redox potential and hydrophilic character. The antiproliferative activity of diferrocenyl derivatives studied herein could be described either with the redox potential, the energy of electronic transitions, logP, or the calculated HOMO-LUMO values. Compound 3d presents the highest antiproliferative activity of the series with an IC50 of 23 µM. However, the results of this work provide a pipeline to improve the amoebicidal activity of these compounds through the directed modification of their electronic environment.

4,5-Diferrocenyl-1,2-di-thiole-3-thione.

The structure of 4,5-diferrocenyl-1,2-di-thiole-3-thione, [Fe2(C5H5)2(C13H8S3)] or C23H18Fe2S3, at 130 K has monoclinic (P21/c) symmetry. The molecule has two ferrocenyl units attached to a 1,2-di-thiole-3-thione moiety. It is of inter-est with respect to the question if the introduction of ferrocenyl substituents into biologically active mol-ecules offers the potential to obtain more efficacious therapeutic drugs. The crystal structure displays inter-molecular contacts of the C-H⋯S and S-π(C-C) types.

Bis-cations with two 2,3-diferrocenylcyclopropenium fragments stabilized with diamino-alkanes: Synthesis and cytotoxic activity.

Bis-cations with two 2,3-diferrocenylcyclopropenium fragments 3a-d, and the cis-2-(1,2-diferrocenylvinyl)-2-imidazolinium tetrafluoroborates 4a, d or the cis-2-(1,2-diferrocenylvinyl)-3,4,5,6-tetrahydropyrimidin-2-ium tetrafluoroborates 4b, c were obtained by interactions of 2,3-diferrocenyl-1-ethoxycyclopropenium tetrafluoroborate 1 with bis-1,4-N,N-(2a, d) or bis-1,5-N,N-(2b, c) nucleophiles. The reactions of 3a-d with sodium azide proceed with high regioselectivity, forming tetraferrocenyl-substituted compounds: N,N'-bis-(4',6'-diferrocenyl-1',2',3'-triazin-5'-yl)-piperazine 5a, N,N'-bis-(4',6'-diferrocenyl-1',2',3'-triazin-5'-yl)-N,N'-dialkyl-1,3- or 1,2-alkanediamines 5b-d. Sodium hydrogencyanamide reacts with 3a-d to form N,N'-bis-(1'-aza-1'-cyano-3',4'-diferrocenyl-1',3'-butadien-2'-yl)-piperazine 6a, N,N'-dialkyl-1,3- or 1,2-alkanediamines 6b-d and N-(1'-cyano-3',4'-diferrocenyl-1'-aza-1',3'-butadien-2'-yl)-N,N'-dialkyl-alkanediamines 7a-d. The characterization of new compounds was done by IR, 1H and 13C NMR spectroscopy, mass-spectrometry, elemental analysis, and X-ray diffraction analysis only for the compounds 4b, 4d, and 7a. The biological activity of compounds 5a, 6a, 6b, 6c was assessed regarding anticancer activity against U-251, K-562, SKLU-1, HCT-15, and MCF-7 cell lines. All tested compounds showed good activity but compounds 6a and 6b had the best anticancer activity against U-251 (human glioblastoma) and SKLU-1 (human lung adenocarcinoma) cultures.

Polycyclic ferrocenyl(dihydro)thiazepine derivatives: Diastereo-selective synthesis, characterization, electrochemical behavior, theoretical and biological investigation.

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 and 13C 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.