RESUMEN

The title compound, C10H8BrN3OS2, a brominated di-thio-carbazate imine deriv-ative, was obtained from the condensation reaction of S-methyl-dithio-carbazate (SMDTC) and 5-bromo-isatin. The essentially planar mol-ecule exhibits a Z configuration, with the di-thio-carbazate and 5-bromo-isatin fragments located on the same sides of the C=N azomethine bond, which allows for the formation of an intra-molecular N-H⋯Ob (b = bromo-isatin) hydrogen bond generating an S(6) ring motif. In the crystal, adjacent mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, forming dimers characterized by an R 2 2(8) loop motif. In the extended structure, mol-ecules are linked into a three-dimensional network by C-H⋯S and C-H⋯Br hydrogen bonds, C-Br⋯S halogen bonds and aromatic π-π stacking.

RESUMEN

The current article reports the investigation of three new Ni(II) complexes with ONS-donor dithiocarbazate ligands: [Ni(L1)PPh3] (1), [Ni(L2)PPh3] (2), and [Ni(L2)Py] (3). Single-crystal X-ray analyses revealed mononuclear complexes with a distorted square planar geometry and the metal centers coordinated with a doubly deprotonated dithiocarbazate ligand and coligand pyridine or triphenylphosphine. The non-covalent interactions were investigated by the Hirshfeld surface and the results revealed that the strongest interactions were π⋅⋅⋅π stacking interactions and non-classical hydrogen bonds C-H···H and C-H···N. Physicochemical and spectroscopic methods indicate the same structures in the solid state and solution. The toxicity effects of the free ligands and Ni(II) complexes were tested on the human breast cancer cell line MCF-7 and non-malignant breast epithelial cell line MCF-10A. The half-maximal inhibitory concentration (IC50) values, indicating that the compounds were potent in inhibiting cell growth, were obtained for both cell lines at three distinct time points. While inhibitory effects were evident in both malignant and non-malignant cells, all three complexes demonstrated lower IC50 values for malignant breast cell lines than their non-malignant counterparts, suggesting a stronger impact on cancerous cell lines. Furthermore, molecular docking studies were performed showing the complex (2) as a promising candidate for further therapeutic exploration.

Asunto(s)

Antineoplásicos , Complejos de Coordinación , Simulación del Acoplamiento Molecular , Níquel , Humanos , Níquel/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Ligandos , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Línea Celular Tumoral , Cristalografía por Rayos X , Células MCF-7 , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Diseño de Fármacos

RESUMEN

The title compound, C16H12FN3OS, a fluorinated di-thio-carbazate imine derivative, was synthesized by the one-pot, multi-component condensation reaction of hydrazine hydrate, carbon di-sulfide, 4-fluoro-benzyl chloride and isatin. The compound demonstrates near-planarity across much of the mol-ecule in the solid state and a Z configuration for the azomethine C=N bond. The Z form is further stabilized by the presence of an intra-molecular N-H⋯O hydrogen bond. In the extended structure, mol-ecules are linked into dimers by N-H⋯O hydrogen bonds and further connected into chains along either [20] or [100] by weak C-H⋯S and C-H⋯F hydrogen bonds, which further link into corrugated sheets and in combination form the overall three-dimensional network.

RESUMEN

The title compound, C17H15N3OS2 was obtained from the condensation reaction of S-benzyl-dithio-carbazate and 5-methyl-isatin. In the solid-state, the mol-ecule adopts a Z configuration with the 5-methyl-isatin and di-thio-carbazate groups located on the same side of the C=N bond, involving an intra-molecular N-H⋯O hydrogen bond.

RESUMEN

In the search for new metal complexes with antitumor potential, two dithiocarbazate ligands derived from 1,1,1-trifluoro-2,4-pentanedione (H2L1) and (H2L2) and four Ni(II) complexes, [Ni(L1)PPh3] (1), [Ni(L1)Py] (2), [Ni(L2)PPh3] (3), and [Ni(L2)Py] (4), were successfully synthesized and investigated by physical-chemistry and spectroscopic methods. The crystal structure of the H2L1 and the Ni(II) complexes has been elucidated by single-crystal X-ray diffraction. The obtained structure from H2L1 confirms the cyclization reaction and formation of the pyrazoline derivative. The results showed square planar geometry to the metal centers, in which dithiocarbazates coordinated by the ONS donor system and a triphenylphosphine or pyridine molecule complete the coordination sphere. Hirshfeld surface analysis by d norm function was investigated and showed π-π stacking interactions upon the molecular packing of H2L1 and non-classical hydrogen bonds for all compounds. Fingerprint plots showed the main interactions attributed to H⋅H C⋅H, O⋅H, Br⋅H, and F⋅H, with contacts contributing between 1.9% and 38.2%. The mass spectrometry data indicated the presence of molecular ions [M + H]+ and characteristic fragmentations of the compounds, which indicated the same behavior of the compounds in solution and solid state. Molecular docking simulations were studied to evaluate the properties and interactions of the free dithiocarbazates and their Ni(II) complexes with selected proteins and DNA. These results were supported by in vitro cytotoxicity assays against four cancer cell lines, showing that the synthesized metal complexes display promising biological activity.

RESUMEN

Schistosomiasis or bilharzia is caused by blood flukes of the genus Schistosoma and represents a considerable health and economic burden in tropical and subtropical regions. The treatment of this infectious disease relies on one single drug: praziquantel (PZQ). Therefore, new and potent antischistosomal compounds need to be developed. In our previous work, starting with the drug disulfiram, we developed dithiocarbamates with in vitro antischistosomal activities in the low micromolar range. Based on these results, we report in this study on the synthesis and biological testing of the structurally related dithiocarbazates against Schistosoma mansoni, one of the major species of schistosomes. In total, three series of dithiocarbazate derivatives were examined, and we found that the antischistosomal activity of N-unbranched dithiocarbazates increased by further N-substitution. Comparable tetra-substituted dithiocarbazates were rarely described in the literature, thus a synthesis route was established. Due to the elaborate synthesis, the branched dithiocarbazates (containing an N-aminopiperazine) were simplified, but the resulting branched dithiocarbamates (containing a 4-aminopiperidine) were considerably less active. Taken together, dithiocarbazate-containing compounds with an in vitro antischistosomal activity of 5 µM were obtained.

Asunto(s)

Esquistosomiasis , Esquistosomicidas , Humanos , Animales , Esquistosomicidas/farmacología , Relación Estructura-Actividad , Esquistosomiasis/tratamiento farmacológico , Praziquantel/farmacología , Praziquantel/uso terapéutico , Schistosoma mansoni

RESUMEN

The nitro-gen-sulfur Schiff base proligand S-n-octyl 3-(1-phenyl-ethyl-idene)di-thio-carbazate, C17H26N2S2 (HL), was prepared by reaction of S-octyl di-thio-carbamate with aceto-phenone. Treatment of HL with nickel acetate yielded the complex bis-[S-n-octyl 3-(1-phenyl-ethyl-idene)di-thio-carbazato]nickel(II), [Ni(C17H25N2S2)2] (NiL 2), which was shown to adopt a tetra-hedrally distorted cis-square-planar coordination geometry, with the NiSN planes of the two ligands forming a dihedral angle of 21.66 (6)°. Changes in the geometry of the L ligand upon chelation of Ni2+ are described, involving a ca 180° rotation around the N(azomethine)-C(thiol-ate) bond.

RESUMEN

The present work reports the synthesis and investigation by semi-empirical Density Functional Theory (DFT), physical chemistry, and spectroscopic methods of two dithiocarbazates, 2-acetylpyridine-S-p-bromobenzyl-dithiocarbazate (HL1) and 2-acetylpyridine-S-p-nitrobenzyl-dithiocarbazate (HL2) and their Cu(II) complexes, [Cu(L1)Cl] (1), [Cu(L1)Br] (2), [Cu(L2)Cl] (3) and [Cu(L2)Br] (4). Single crystal X-ray analyzes showed distorted square planar geometry to the metal centers, which tridentate ligands coordinated by the NNS system and an additional halogen (Cl- or Br-) to complete the coordination sphere. Mass spectrometry data indicated the presence of [Cu(L1)(DMF)]+ and [Cu(L2)(DMF)]+, due to the exchanging of chloride/bromide ions and characteristic fragmentations of the compounds. The DFT composite method B97-3c was employed to optimize the geometries of ligands and complexes and IR spectra were calculated revealing good agreement with experimental data. Hydrogen bonds and π⋅⋅⋅π stacking interactions upon the molecular packing were investigated by Hirshfeld surface and fingerprint plots with the main interactions attributed to the H⋅⋅⋅H contacts. The biological activity of the dithiocarbazates and their Cu(II) complexes were evaluated in vitro against the human glioma U251 cells. Results revealed that the free dithiocarbazates present great in vitro antitumor activity that is increased after the complexation with copper. The measurement of cytotoxicity of the compounds showed biological activity in a low range of concentration, which indicates high efficiency as potential drugs.

Asunto(s)

Complejos de Coordinación , Cobre , Humanos , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Cobre/química , Cristalografía por Rayos X , Halógenos , Enlace de Hidrógeno , Ligandos , Metales/química

RESUMEN

In this work, one oxidomethoxidovanadium(V) [VVO(L)(OMe)] (1) and two mixed-ligand oxidovanadium(IV) [VIVO(L)(phen)] (2), and [VIVO(L)(bipy)] (3) complexes have been synthesized using a tridentate bi-negative ONS donor dithiocarbazate as main ligand, H2L [where, H2L = S-benzyl-3-(2-hydroxy-3-ethoxyphenyl)methylenedithiocarbazate] along with 1,10-phenanthroline (phen) (for 2) and 2,2'-bipyridine (bipy) (for 3) as co-ligands. The ligand and complexes have been characterised by FT-IR, UV-vis, NMR, and HR-ESI-MS techniques. Distorted square pyramidal for 1, and distorted octahedral geometry for 2 and 3 was confirmed by single crystal X-ray crystallography. The behavior of 1-3 in solution medium has been investigated through various physicochemical techniques. It is observed that 1 completely and 2-3 partially decomposes and converts into a penta-coordinated species, [VIVO(L)(DMSO/H2O)] after the release of the methoxido group (1) or breaking of the diimine based co-ligands (2 and 3) in DMSO/aqueous solution. Interestingly, in DMSO/aqueous solution, 1 gets completely reduced and converted into the corresponding oxidovanadium(IV) species. Interaction of 1-3 with calf thymus DNA (CT-DNA) was investigated and the results show, complex 2 exhibited the maximum binding constants, Kb = 7.12 × 104 M-1. The anticancer potential of 1-3 was evaluated by cell viability assay against human breast carcinoma cell, MCF-7, and noncancerous mouse embryonic cell, NIH-3T3 and 2 was found to be the most cytotoxic complex (IC50 = 6.73 ± 0.36 µM) in the series. In addition, 2 selectively inhibit colony formation compared to the rest complexes. Also, the cell cycle studies of the complexes were performed using flow cytometry analysis.

Asunto(s)

Complejos de Coordinación , Dimetilsulfóxido , Animales , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Cristalografía por Rayos X , ADN/química , Ligandos , Ratones , Fenantrolinas/química , Espectroscopía Infrarroja por Transformada de Fourier

RESUMEN

The present work reports the synthesis and a structural study of two novel dithiocarbazate, the 4,6-diacetylresorcinol-S-benzyldithiocarbazate (H3L1) and the 4,6-diacetylresorcinol-bis(S-benzyldithiocarbazate) (H4L2), and their Ni(II) complexes, [Ni(HL1)(Py)] (1) and [Ni2(L2)(PPh3)2] (2). Single crystal X-ray analyzes reveal mono and binuclear complexes and the metal centers with distorted square planar geometry. The analyses of the Hirshfeld surface and fingerprints plots revealed intermolecular contacts attributed to the H···H and C···H/H···C bonds. The Density Functional Theory (DFT), with the B3LYP functional and 6-311-G(d,p)/LanL2DZ basis sets, was employed to optimize the geometries of synthesized compounds. From the resulting geometries, the highest occupied and lowest unoccupied molecular orbital maps (HOMO-LUMO), orbital energy gap, electron localization function (ELF), electron density, natural bond orbital (NBO) analysis, and complexation of the ligands with Ni(II) were calculated supporting the experimental data. The ESI (+)-MS/MS data indicated the presence in solution of the characteristic fragmentation with the [H3L1]+ and [H4L2]+ molecular ions for the ligands. The pharmacological potential of the dithiocarbazate ligands and their Ni(II) complexes were evaluated in vitro against MDA-MB-231 human breast cancer cells. A remarkable cytotoxic activity was observed, more evident for free ligands than complexes at low concentrations; however, this latter showed a better dose-response pattern, being more attractive in terms of pharmacokinetics and therapeutic window.

Asunto(s)

Complejos de Coordinación/química , Hidrazinas/química , Níquel/química , Resorcinoles/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/farmacología , Cristalografía por Rayos X/métodos , Teoría Funcional de la Densidad , Humanos , Hidrazinas/farmacología , Ligandos , Estructura Molecular , Níquel/farmacología , Resorcinoles/farmacología , Espectrometría de Masas en Tándem/métodos

RESUMEN

Schiff bases (SB) obtained from S-methyl dithiocarbazate and aromatic aldehydes: salicylaldehyde (H2L1), o-vanillin (H2L2), pyridoxal (H2L3) and 2,6-diformyl-4-methylphenol (H3L4), and their corresponding Zn(II)-complexes (1-4), are synthesized. All compounds are characterized by elemental analyses, infrared, UV-Vis, nuclear magnetic resonance spectroscopy and mass spectrometry. The structures of H2L2 and [Zn2(L1)2(H2O)(DMF)] (1a) (DMF = dimethylformamide) are solved by single crystal X-ray diffraction. The SB coordinates the metal center through the Ophenolate, Nimine and Sthiolate atoms. The radical scavenging activity is tested using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, with all ligand precursors showing IC50 values ~40 µM. Cytotoxicity studies with several tumor cell lines (PC-3, MCF-7 and Caco-2) as well as a non-tumoral cell line (NHDF) are reported. Interestingly, 1 has relevant and selective antiproliferative effect against Caco-2 cells (IC50 = 9.1 µM). Their antimicrobial activity is evaluated in five bacterial strains (Klebsiella pneumoniae, Acinetobacter baumannii, Listeria monocytogenes, Pseudomonas aeruginosa and Staphylococcus aureus) and two yeast strains (Candida albicans and Candida tropicalis) with some compounds showing bacteriostatic and fungicidal activity. The minimal inhibitory concentration (MIC90) of HnL against Mycobacterium tuberculosis is also reported, with H2L2 and H3L4 showing very high activity (MIC90 < 0.6 µg/mL). The ability of the compounds to bind bovine serum albumin (BSA) and DNA is evaluated for H3L4 and [Zn2(L4)(CH3COO)] (4), both showing high binding constants to BSA (ca. 106 M-1) and ability to bind DNA. Overall, the reported compounds show relevant antitumor and antimicrobial properties, our data indicating they may be promising compounds in several fields of medicinal chemistry.

Asunto(s)

Antiinfecciosos , Antineoplásicos , Bacterias/crecimiento & desarrollo , Candida albicans/crecimiento & desarrollo , Candida tropicalis/crecimiento & desarrollo , Complejos de Coordinación , Neoplasias/tratamiento farmacológico , Zinc , Antiinfecciosos/síntesis química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Células CACO-2 , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Humanos , Células MCF-7 , Neoplasias/metabolismo , Neoplasias/patología , Células PC-3 , Bases de Schiff/síntesis química , Bases de Schiff/química , Bases de Schiff/farmacología , Zinc/química , Zinc/farmacología

RESUMEN

The structures are described of two bis-chelated metal complexes of nickel(II) and copper(II) with S-n-hexyl 3-(1-phenyl-ethyl-idene)di-thio-carbazate Schiff bases in a cis configuration, namely, bis-[S-n-hexyl 3-(1-phenyl-ethyl-idene)di-thio-carbazato-κ2 N 3,S]nickel(II), [Ni(C15H21N2S2)2], and bis-[S-n-hexyl 3-(1-phenyl-ethyl-idene)di-thio-carbazato-κ2 N 3,S]copper(II), [Cu(C15H21N2S2)2]. In both complexes, the metals have distorted square-planar geometries. A search in the Cambridge Structural Database [Groom et al. (2016 ▸). Acta Cryst. B72, 171-179] for bis-chelated nickel(II) and copper(II) complexes with similar Schiff bases retrieved 55 and 36 hits for the two metals, respectively. An analysis of the geometrical parameters of complexes showing cis and trans configurations is reported and the values compared with those for the complexes described in this work.

RESUMEN

Development of new chemotherapeutic agents and strategies are urgently needed to curb and halt the growing menace caused by hard-to-treat microbes. Coordination of metals to bioactive organic ligands is now considered to be an efficient strategy for delivering bioactive compounds inside the microbial cell membranes. Metal complexes have been effectively used to treat many dreadful diseases were other treatment modalities had failed. Use of metal complexes to treat microbial infections is now conceived to be an alternative and efficient strategy. Towards this, some new homoleptic transition metal complexes, obtained by coordination of metal ions to bioactive S-benzyldithiocarbazate Schiff-base ligands were evaluated for their anti-Candida activity and their potential to disrupt the membrane architecture. The complexes displayed remarkable antifungal activity against a wide spectrum of fluconazole susceptible and resistant Candida albicans isolates, with Ni complex (dtc3) being highly active with minimum inhibitory concentration (MIC) values ranging from 1 to 32 µg/mL. Cell viability assay confirmed the fungicidal activity of these metal complexes, especially the complex dtc3. These metal complexes kill Candida albicans by inducing cellular apoptosis and necrosis thereby causing phosphatidylserine externalization as revealed by Annexin V-FITC and propidium iodide staining assays.

Asunto(s)

Antifúngicos/farmacología , Apoptosis/efectos de los fármacos , Candida albicans/efectos de los fármacos , Complejos de Coordinación/farmacología , Hidrazinas/farmacología , Iminas/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Relación Dosis-Respuesta a Droga , Hidrazinas/química , Iminas/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-Actividad

RESUMEN

A series of Schiff bases have been successfully synthesized through the acid-catalyzed condensation of S-substituted dithiocarbazates and three enantiomerically pure monoterpenes, (1 R )-(+)-camphor, (1 S )-(-)-camphor, (1 R )-(-)-camphorquinone, (1 S )-(+)-camphorquinone, ( R )-(-)-carvone and ( S )-(+)-carvone. Spectroscopic results revealed that the Schiff bases containing camphor or carvone likely adopted an E -configuration along the characteristic imine bond while those containing camphorquinone assumed a Z -configuration. The antidengue potential of these compounds was evaluated based on DENV 2 caused cytopathic effect (CPE) reduction-based in vitro evaluation. The compounds were validated through secondary foci forming unit reduction assay (FFURA). Compounds were also tested for their cytotoxicity against Vero cells. The compounds showed variable degrees of antiviral activity with the camphor compounds displaying the highest antidengue potential. The enantiomers of the compounds behaved almost similarly during the antiviral evaluation.

RESUMEN

Six new organotin(IV) compounds of Schiff bases derived from S-R-dithiocarbazate [R = benzyl (B), 2- or 4-methylbenzyl (2M and 4M, respectively)] condensed with 2-hydroxy-3-methoxybenzaldehyde (oVa) were synthesised and characterised by elemental analysis, various spectroscopic techniques including infrared, UV-vis, multinuclear (¹H, 13C, 119Sn) NMR and mass spectrometry, and single crystal X-ray diffraction. The organotin(IV) compounds were synthesised from the reaction of Ph2SnCl2 or Me2SnCl2 with the Schiff bases (S2MoVaH/S4MoVaH/SBoVaH) to form a total of six new organotin(IV) compounds that had a general formula of [R2Sn(L)] (where L = Schiff base; R = Ph or Me). The molecular geometries of Me2Sn(S2MoVa), Me2Sn(S4MoVa) and Me2Sn(SBoVa) were established by X-ray crystallography and verified using density functional theory calculations. Interestingly, each experimental structure contained two independent but chemically similar molecules in the crystallographic asymmetric unit. The coordination geometry for each molecule was defined by thiolate-sulphur, phenoxide-oxygen and imine-nitrogen atoms derived from a dinegative, tridentate dithiocarbazate ligand with the remaining positions occupied by the methyl-carbon atoms of the organo groups. In each case, the resulting five-coordinate C2NOS geometry was almost exactly intermediate between ideal trigonal-bipyramidal and square-pyramidal geometries. The cytotoxic activities of the Schiff bases and organotin(IV) compounds were investigated against EJ-28 and RT-112 (bladder), HT29 (colon), U87 and SJ-G2 (glioblastoma), MCF-7 (breast) A2780 (ovarian), H460 (lung), A431 (skin), DU145 (prostate), BE2-C (neuroblastoma) and MIA (pancreatic) cancer cell lines and one normal breast cell line (MCF-10A). Diphenyltin(IV) compounds exhibited greater potency than either the Schiff bases or the respective dimethyltin(IV) compounds. Mechanistic studies on the action of these compounds against bladder cancer cells revealed that they induced the production of reactive oxygen species (ROS). The bladder cancer cells were apoptotic after 24 h post-treatment with the diphenyltin(IV) compounds. The interactions of the organotin(IV) compounds with calf thymus DNA (CT-DNA) were experimentally explored using UV-vis absorption spectroscopy. This study revealed that the organotin(IV) compounds have strong DNA binding affinity, verified via molecular docking simulations, which suggests that these organotin(IV) compounds interact with DNA via groove-binding interactions.

Asunto(s)

Benzaldehídos/síntesis química , Benzaldehídos/farmacología , Simulación por Computador , Compuestos Orgánicos de Estaño/síntesis química , Compuestos Orgánicos de Estaño/farmacología , Bases de Schiff/síntesis química , Bases de Schiff/farmacología , Benzaldehídos/química , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Cristalografía por Rayos X , ADN/metabolismo , Humanos , Cinética , Conformación Molecular , Simulación del Acoplamiento Molecular , Compuestos Orgánicos de Estaño/química , Especies Reactivas de Oxígeno/metabolismo , Bases de Schiff/química

RESUMEN

In the title di-thio-carbazate ester, C16H17N3S2 (systematic name: (Z)-{[(benzyl-sulfan-yl)methane-thio-yl]amino}[1-(6-methyl-pyridin-2-yl)ethyl-idene]amine), the central methyl-idenehydrazinecarbodi-thio-ate (C2N2S2) core is almost planar (r.m.s. deviation = 0.0111 Å) and forms dihedral angles of 71.67 (3)° with the approximately orthogonally inclined thio-ester phenyl ring, and 7.16 (7)° with the approximately coplanar substituted pyridyl ring. The latter arrangement and the Z configuration about the imine-C=N bond allows for the formation of an intra-molecular hydrazine-N-H⋯N(pyrid-yl) hydrogen bond that closes an S(6) loop. In the crystal, phenyl-C-H⋯S(thione), methyl-ene-C-H⋯π(pyrid-yl), methyl-ene- and phenyl-C-H⋯π(phen-yl) contacts connect mol-ecules into supra-molecular layers propagating in the bc plane; the layers stack along the a axis with no directional inter-actions between them. The analysis of the Hirshfeld surface indicates the relative importance of an intra-layer phenyl-H⋯H(pyrid-yl) contact upon the mol-ecular packing.

RESUMEN

The title di-thio-carbazate ester (I), C18H18N2S2 [systematic name: (E)-4-methyl-benzyl 2-[(E)-3-phenyl-allyl-idene]hydrazinecarbodi-thio-ate, comprises an almost planar central CN2S2 residue [r.m.s. deviation = 0.0131 Å]. The methyl-ene(tolyl-4) group forms a dihedral angle of 72.25 (4)° with the best plane through the remaining non-hydrogen atoms [r.m.s. deviation = 0.0586 Å] so the mol-ecule approximates mirror symmetry with the 4-tolyl group bis-ected by the plane. The configuration about both double bonds in the N-N=C-C=C chain is E; the chain has an all trans conformation. In the crystal, eight-membered centrosymmetric thio-amide synthons, {⋯HNCS}2, are formed via N-H⋯S(thione) hydrogen bonds. Connections between the dimers via C-H⋯π inter-actions lead to a three-dimensional architecture. A Hirshfeld surface analysis shows that (I) possesses an inter-action profile similar to that of a closely related analogue with an S-bound benzyl substituent, (II). Computational chemistry indicates the dimeric species of (II) connected via N-H⋯S hydrogen bonds is about 0.94 kcal mol-1 more stable than that in (I).

RESUMEN

The title di-thio-carbazate ester, C16H16N2O2S2, comprises two almost planar residues, i.e. the phenyl ring and the remaining 14 non-H atoms (r.m.s. deviation = 0.0410 Å). These are orientated perpendicularly, forming a dihedral angle of 82.72 (5)°. An intra-molecular hy-droxy-O-H⋯N(imine) hydrogen bond, leading to an S(6) loop, is noted. An analysis of the geometric parameters is consistent with the mol-ecule existing as the thione tautomer, and the conformation about the C=N bond is E. The thione S and imine H atoms lie to the same side of the mol-ecule, facilitating the formation of inter-molecular N-H⋯S hydrogen bonds leading to eight-membered {⋯HNCS}2 synthons in the crystal. These aggregates are connected by phenyl-C-H⋯O(hy-droxy) inter-actions into a supra-molecular layer in the bc plane; these stack with no directional inter-actions between them. An analysis of the Hirshfeld surface confirms the nature of the inter-molecular inter-actions.

RESUMEN

Copper (II) complexes synthesized from the products of condensation of S-methyl- and S-benzyldithiocarbazate with 2,5-hexanedione (SMHDH2 and SBHDH2 respectively) have been characterized using various physicochemical (elemental analysis, molar conductivity, magnetic susceptibility) and spectroscopic (infrared, electronic) methods. The structures of SMHDH2, its copper (II) complex, CuSMHD, and the related CuSBHD complex as well as a pyrrole byproduct, SBPY, have been determined by single crystal X-ray diffraction. In order to provide more insight into the behaviour of the complexes in solution, electron paramagnetic resonance (EPR) and electrochemical experiments were performed. Antibacterial activity and cytotoxicity were evaluated. The compounds, dissolved in 0.5% and 5% DMSO, showed a wide range of antibacterial activity against 10 strains of Gram-positive and Gram-negative bacteria. Investigations of the effects of efflux pumps and membrane penetration on antibacterial activity are reported herein. Antiproliferation activity was observed to be enhanced by complexation with copper. Preliminary screening showed Cu complexes are strongly active against human breast adenocarcinoma cancer cell lines MDA-MB-231 and MCF-7.

Asunto(s)

Cobre/farmacología , Compuestos Macrocíclicos/farmacología , Bases de Schiff/química , Antibacterianos/química , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Línea Celular Tumoral , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Cobre/química , Humanos , Hidrazinas/química , Hidrazinas/farmacología , Compuestos Macrocíclicos/química , Bases de Schiff/farmacología

RESUMEN

The title compound, C14H20N2OS2 [systematic name: S-hexyl (E)-2-(2-hy-droxy-benzyl-idene)hydrazine-1-carbodi-thio-ate], crystallizes with four independent mol-ecules (A-D) in the asymmetric unit. All four mol-ecules adopt an E conformation with respect to the C=N bond of the benzyl-idene moiety and have an intra-molecular O-H⋯N hydrogen bond generating an S(6) ring motif. In the crystal, the A and D mol-ecules are connected by a pair N-H⋯S hydrogen bonds, forming a dimer with an R 2 (2)(8) ring motif. In the case of mol-ecules B and C, they are linked to themselves by pairs of N-H⋯S hydrogen bonds, forming B-B and C-C inversion dimers with R 2 (2)(8) ring motifs.