RESUMEN
In this paper, three different Zn(II) complexes with (E)-2-(2-(1-(6-bromopyridin-2-yl)ethylidene)hydrazinyl)-N,N,N-trimethyl-2-oxoethan-1-aminium chloride (HLCl) have been synthesized and characterized by single crystal X-ray diffraction, elemental analysis, IR and NMR spectroscopy. All complexes are mononuclear, with the ligand (L) coordinated in a deprotonated formally neutral zwitterionic form via NNO donor set atoms. Complex 1 forms an octahedral geometry with the composition [ZnL2](BF4)2, while complexes 2 [ZnL(NCO)2] and 3 [ZnL(N3)2] form penta-coordinated geometry. Density functional theory (DFT) calculations were performed to enhance our understanding of the structures of the synthesized complexes and the cytotoxic activity of the complexes was tested against five human cancer cell lines (HeLa, A549, MDA-MB-231, K562, LS 174T) and normal human fibroblasts MRC-5. Additionally, antibacterial and antifungal activity of these complexes was tested against a panel of Gram-negative and Gram-positive bacteria, two fungal strains, and a yeast strain. It is noteworthy that all three complexes show selective antifungal activity comparable to that of amphotericin B. Molecular docking analysis predicted that geranylgeranyl pyrophosphate synthase, an enzyme essential for sterol biosynthesis, is the most likely target for inhibition by the tested complexes.
Asunto(s)
Antibacterianos , Antifúngicos , Antineoplásicos , Complejos de Coordinación , Teoría Funcional de la Densidad , Hidrazonas , Pruebas de Sensibilidad Microbiana , Zinc , Humanos , Hidrazonas/química , Hidrazonas/farmacología , Hidrazonas/síntesis química , Zinc/química , Zinc/farmacología , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Línea Celular Tumoral , Estructura Molecular , Simulación del Acoplamiento Molecular , Ensayos de Selección de Medicamentos Antitumorales , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Modelos Moleculares , Hongos/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
In this paper, Cu(II), Mn(II) and Zn(II) complexes with N,N,N-trimethyl-2-oxo-2-(2-(1-(thiazol-2-yl)ethylidene)hydrazinyl)ethan-1-aminium chloride (HL1Cl) were synthesized and characterized by single-crystal X-ray diffraction, IR spectroscopy, elemental analysis and DFT calculations. In all three complexes, a ligand (L1) is coordinated in a deprotonated formally neutral zwitterionic form via NNO donor set atoms. Cu(II) and Zn(II) form mononuclear penta-coordinated complexes [CuL1(N3)(CH3OH)]BF4 and [ZnL1(N3)2], respectively, while Mn(II) forms a binuclear [Mn2L12(µ-1,1-N3)2(N3)2]·2CH3OH complex, with unusual distorted trigonal-prismatic geometry around the metal centers. The antimicrobial activity of these complexes was tested against a panel of Gram-negative and Gram-positive bacteria, two yeasts and one fungal strain. The binuclear Mn(II) complex showed antifungal activity of similar intensity to amphotericin B. Based on the results of the brine shrimp test and DPPH radical scavenging activity, the most active Cu(II) and Mn(II) complexes were selected for evaluation of cytotoxic activity against five malignant cancer cell lines (HeLa, A375, MCF7, PC-3 and A549) and one normal cell line HaCaT. Both complexes showed significant activity. It should be pointed out that the activity of the Mn(II) complex against the MCF7 breast cancer cell line is only slightly weaker than that of cisplatin, but with selectivity to the tumor cell line in comparison to normal HaCaT cells, which is non-existent in the case of cisplatin.
Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Antineoplásicos/farmacología , Antioxidantes/farmacología , Complejos de Coordinación/farmacología , Teoría Funcional de la Densidad , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Antioxidantes/síntesis química , Antioxidantes/química , Artemia/efectos de los fármacos , Compuestos de Bifenilo/antagonistas & inhibidores , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Cobre/química , Cobre/farmacología , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Hongos/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Hidrazonas/química , Hidrazonas/farmacología , Manganeso/química , Manganeso/farmacología , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Picratos/antagonistas & inhibidores , Compuestos de Amonio Cuaternario/química , Compuestos de Amonio Cuaternario/farmacología , Zinc/química , Zinc/farmacologíaRESUMEN
Two new Zn(II) complexes with tridentate hydrazone-based ligands (condensation products of 2-acetylthiazole) were synthesized and characterized by infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy and single crystal X-ray diffraction methods. The complexes 1, 2 and recently synthesized [ZnL3(NCS)2] (L3 = (E)-N,N,N-trimethyl-2-oxo-2-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)ethan-1-aminium) complex 3 were tested as potential catalysts for the ketone-amine-alkyne (KA2) coupling reaction. The gas-phase geometry optimization of newly synthesized and characterized Zn(II) complexes has been computed at the density functional theory (DFT)/B3LYP/6-31G level of theory, while the highest occupied molecular orbital and lowest unoccupied molecular orbital (HOMO and LUMO) energies were calculated within the time-dependent density functional theory (TD-DFT) at B3LYP/6-31G and B3LYP/6-311G(d,p) levels of theory. From the energies of frontier molecular orbitals (HOMO-LUMO), the reactivity descriptors, such as chemical potential (µ), hardness (η), softness (S), electronegativity (χ) and electrophilicity index (ω) have been calculated. The energetic behavior of the investigated compounds (1 and 2) has been examined in gas phase and solvent media using the polarizable continuum model. For comparison reasons, the same calculations have been performed for recently synthesized [ZnL3(NCS)2] complex 3. DFT results show that compound 1 has the smaller frontier orbital gap so, it is more polarizable and is associated with a higher chemical reactivity, low kinetic stability and is termed as soft molecule.
Asunto(s)
Teoría Funcional de la Densidad , Hidrazonas/química , Hidrazonas/síntesis química , Zinc/química , Catálisis , Cristalografía por Rayos X , Conformación Molecular , Teoría Cuántica , TermodinámicaRESUMEN
(1-(2,4-Dioxo-1,2,3,4-tetrahydroquinolin-3-yl)-1H-1,2,3-triazol-4-yl)methyl acetates substituted on nitrogen atom of quinolinedione moiety with propargyl group or (1-substituted 1H-1,2,3-triazol-4-yl)methyl group, which are available from the appropriate 3-(4-hydroxymethyl-1H-1,2,3-triazol-1-yl)quinoline-2,4(1H,3H)-diones unsubstituted on quinolone nitrogen atom by the previously described procedures, were deacetylated by acidic ethanolysis. Thus obtained primary alcohols, as well as those aforenamed unsubstituted on quinolone nitrogen atom, were oxidized to aldehydes on the one hand with pyridinium chlorochromate (PCC), on the other hand with manganese dioxide, and to carboxylic acids using Jones reagent in acetone. The structures of all prepared compounds were confirmed by 1H, 13C and 15N NMR spectroscopy. The corresponding resonances were assigned on the basis of the standard 1D and gradient selected 2D NMR experiments (1H-1H gs-COSY, 1H-13C gs-HSQC, 1H-13C gs-HMBC) with 1H-15N gs-HMBC as a practical tool to determine 15N NMR chemical shifts at the natural abundance level of 15N isotope.
RESUMEN
The reaction of N-(2-pyridyl)thiourea with CuCl2 in methanol yields four different crystalline products: yellow dimeric complex, [Cu2Cl2(?-Cl)2(L)2] (1), red polymeric complex, [Cu3Cl8L2]n (2), orange crystalline product with ionic structure, L2[CuCl4] (3), and colourless ionic compound LCl (4), where L = 2-amino-[1,2,4]thiadiazolo[2,3-a]pyridin-4-ium cation as a result of oxidative cyclization of N-(2-pyridyl)thiourea. The crystal structures of all these crystalline products have been determined by single-crystal X-ray diffraction analysis. Compound 1 involves a copper(I) ion while in 2 and 3 the copper centre is in the divalent state. 1H NMR spectra for compounds 1-3 are identical and confirm deprotonated thioamide groups of N-(2-pyridyl)thiourea and the formation of a thiadiazolopyridinium cation in solution. The hydrogen bonding and ?-? stacking interactions were investigated in the solid state. In addition, all crystalline products 1-4 exhibit also S···Cl bonding interactions which consolidate the complexes into networks. The X-ray diffraction analyses indicate the absence of other crystalline phases in the crude reaction mixture.
RESUMEN
In this work synthesis, characterization and crystal structures of two isothiocyanato Fe(III) complexes with 2,2'-[2,6-pyridinediylbis(ethylidyne-1-hydrazinyl-2-ylidene)]bis[N,N,N-trimethyl-2-oxoethanaminium] dichloride (H2LCl2) ligand, with composition [FeL(NCS)2]SCN·2H2O and [FeL(NCS)2]2[Fe(H2O)(NCS)5]·4H2O, has been reported. Both iron(III) complexes possess the same pentagonal-bipyramidal complex cation, while the nature of their anions depends on mole ratio of NH4SCN and FeCl3·6H2O used in reaction. Cytotoxic activity of new Fe(III) complexes, as well as of previously synthesized isothiocyanato Co(II), Ni(II), Mn(II), Zn(II) and Cd(II) complexes with the same ligand, was tested against five human cancer cell lines (HeLa, MDA-MB-453, K562, LS174 and A549) and normal cell line MRC-5. The best activity was observed in the case of Fe(III), Co(II) and Cd(II) complexes. The investigation of potential of these complexes to induce HeLa and K562 cell cycle perturbations was also evaluated. Mechanism of cell death mode was elucidated on the basis of morphological changes of HeLa cells as well as identification of target caspases. It was established that DNA damage could be responsible for the activity of Fe(III) and Co(II) complexes. SYNOPSIS: Pentagonal-bipyramidal Fe(III) complexes with dihydrazone of 2,6-diacetylpyridine and Girard's T reagent have been synthesized and characterized. Cytotoxic activity of Fe(III) complexes and Co(II), Ni(II), Mn(II), Zn(II) and Cd(II) complexes with the same ligand was tested. The best activity was observed in the case of Fe(III), Co(II) and Cd(II) complexes.
Asunto(s)
Antineoplásicos , Betaína/análogos & derivados , Ciclo Celular/efectos de los fármacos , Compuestos Férricos , Hidrazonas , Piridinas , Células A549 , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Betaína/química , Betaína/farmacología , Muerte Celular/efectos de los fármacos , Daño del ADN , Compuestos Férricos/síntesis química , Compuestos Férricos/química , Compuestos Férricos/farmacología , Células HeLa , Humanos , Hidrazonas/química , Hidrazonas/farmacología , Células K562 , Piridinas/química , Piridinas/farmacologíaRESUMEN
Novel tetrachloridoruthenium(III) complex Na[trans-RuCl4(DMSO)(PyrDiaz)] (3) with pyridine-tethered diazenedicarboxamide PyrDiaz ligand (PyrDiaz = N1-(4-isopropylphenyl)-N2-(pyridin-2-ylmethyl)diazene-1,2-dicarboxamide) was synthesized by direct coupling of PyrDiaz with sodium trans-bis(dimethyl sulfoxide)tetrachloridoruthenate(III) (Na-[trans-Ru(DMSO)2Cl4]). Compound 3 is the analogue of the antimetastatic Ru(III) complex NAMI-A and NAMI-Pyr. Single crystal X.
Asunto(s)
Antineoplásicos/síntesis química , Dimetilsulfóxido/análogos & derivados , Compuestos Organometálicos/química , Rutenio/química , Antineoplásicos/química , Cristalografía por Rayos X , Dimetilsulfóxido/química , Imidas/síntesis química , Imidas/químicaRESUMEN
A novel bis(pyridyl-functionalized 1,2,3-triazol-5-ylidene)-palladium(II) complex [Pd(Py-tzNHC)2](2+) catalyses the copper-, amine-, phosphine-, and additive-free aerobic Sonogashira alkynylation of (hetero)aryl bromides in water as the only reaction solvent. The catalysis proceeds along two connected Pd-cycles with homogeneous bis-carbene Pd(0) and Pd(II) species, as demonstrated by electrospray ionization mass spectrometry.
RESUMEN
Metal complexes with ML or ML2 stoichiometry have been isolated in the reaction of Zn(NO3)2, ZnBr2 or M(NO3)2/NaBF4, M = Zn(ii), Co(ii) or Ni(ii), with either amino acid or amine substituted tridentate nitrogen ligands based on bis(2-picolyl)amine (bpa) or bis(2-quinaldyl)amine (bqa). The stoichiometry (M : L = 1 : 1 or 1 : 2) and stereochemistry (mer, trans-fac or cis-fac) of the products have been studied by NMR and IR spectroscopy, X-ray single crystal analysis and quantum-chemical calculations with an implicit SMD solvation model.
Asunto(s)
Aminas/química , Aminoácidos/química , Cobalto/química , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Níquel/química , Ácidos Picolínicos/química , Zinc/química , Cristalografía por Rayos X , Ligandos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Espectrometría de Masa por Ionización de Electrospray , EstereoisomerismoRESUMEN
Square-planar azido Ni(II) complex with condensation product of 2-(diphenylphosphino)benzaldehyde and Girard's T reagent was synthesized and its crystal structure was determined. Cytotoxic activity of the azido complex and previously synthesized isothiocyanato, cyanato and chlorido Ni(II) complexes with this ligand was examined on six tumor cell lines (HeLa, A549, K562, MDA-MB-453, MDA-MB-361 and LS-174) and two normal cell line (MRC-5 and BEAS-2B). All the investigated nickel(II) complexes were cytotoxic against all tumor cell lines. The newly synthesized azido complex showed selectivity to HeLa and A549 tumor cell lines compared to the normal cells (for A549 IC50 was similar to that of cisplatin). Azido complex interferes with cell cycle phase distribution of A549 and HeLa cells and possesses nuclease activity towards supercoiled DNA. The observed selectivity of the azido complex for some tumor cell lines can be connected with its strong DNA damaging activity.
Asunto(s)
Antineoplásicos/farmacología , Benzaldehídos/química , Halógenos/química , Hidrazonas/química , Níquel/química , Antineoplásicos/química , Cristalografía por Rayos X , Células HeLa , Humanos , Microscopía Fluorescente , Espectrometría de Fluorescencia , Espectrofotometría Infrarroja , Espectrofotometría UltravioletaRESUMEN
1,3-Diaryltriazenes (1) were let to react with [RuCl2(p-cymene)]2 in the presence of trimethylamine to give neutral 1,3-diaryltriazenido(p-cymene)ruthenium(II) complexes, [RuCl(p-cymene)(ArNNNAr)] (2). The molecular composition of the products 2 was confirmed by NMR spectroscopy and mass spectrometry. The structures of the selected complexes were confirmed by a single crystal X-ray analysis. All triazenido-ruthenium complexes were highly cytotoxic against human cervical carcinoma HeLa cells with IC50 below 6µM, as determined by a spectrophotometric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) method. The most active was [RuCl(p-cymene)(ArNNNAr)] (Ar=4-Cl-3-(CF3)-C6H3) (2g) with IC50 of 0.103±0.006µM. In comparison with the data for the non-coordinated triazenes 1, the triazenido-ruthenium complexes 2 exhibited up to 560-times higher activity. Three selected complexes were highly cytotoxic also against several tumor cell lines: laryngeal carcinoma HEp-2 cells and their drug-resistant HEp-2 subline (7T), colorectal carcinoma HCT-116 cells, lung adenocarcinoma H460 cells, and mammary carcinoma MDA-MB-435 cells. The compounds 2g and [RuCl(p-cymene)(ArNNNAr)] (Ar=4-I-C6H4) (2j) were similarly cytotoxic against parental and drug-resistant cells. Time and dose dependent accumulation of the cells in the S phase of the cell cycle was induced by the compound 2g, triggering apoptosis. Our preliminary results indicate triazenido-ruthenium complexes as promising anticancer drug candidates.
Asunto(s)
Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Triazenos/farmacología , Animales , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Bovinos , Complejos de Coordinación/síntesis química , Cristalografía por Rayos X , ADN/química , Células HeLa , Humanos , Triazenos/síntesis químicaRESUMEN
The synthesis and spectroscopic characterization of some pyrimidinium hexafluoridosilicate salts with the formula (RH)2[SiF]6 (where R = 2-aminopyrimidine (1), cytosine (2) and 5-cyanocytosine (3)) is obtained in the reaction of SiO2 with hydrofluoric acid solution and subsequent addition of 2-aminopyrimidine, cytosine or 4-amino-2-chloropyrimidine-5-carbonitrile. The crystal structures of 1 and 3 have been determined by single-crystal Xâray diffraction analysis. The combination of NâH···F hydrogen bonds along with πâπ interactions between aromatic rings resulted in supramolecular architecture of cations and anions in the solid state.
RESUMEN
The synthesis and characterization of two new zinc(II) coordination compounds with 3- and 4-aminopyridine are reported. They were obtained after adding a water solution of Zn(CH3COO)2·2H2O or dissolving solid Zn(CH3COO)2 â 2H2O in methanol solutions of 3- and 4-aminopyridine. The products were characterized structurally by single-crystal X-ray diffraction analysis. Colourless crystals of the compound synthesized by the reaction of Zn(CH3COO)2·2H2O and 3-aminopyridine (3-apy), are built of trinuclear complex molecules with the formula [Zn3(O2CCH3)6(3-apy)2(H2O)2] (1). The molecules consists of two terminal Zn atoms, coordinated tetrahedrally, and one central Zn atom, coordinated octahedrally. Colourless crystals, obtained by the reaction of Zn(CH3COO)2·2H2O with 4-aminopyridine (4-apy), consist of a mononuclear complex [Zn(O2CCH3)2(4-apy)2] (2). Hydrogenâbonding interactions in the crystal structures of both complexes are reported.
Asunto(s)
Acetatos/síntesis química , Aminopiridinas/síntesis química , 4-Aminopiridina , Acetatos/química , Aminopiridinas/química , Cristalografía por Rayos X , Enlace de Hidrógeno , Acetato de ZincRESUMEN
A general protocol to independently access stereoisomerically pure ß'-hydroxy-ß-amino acid derivatives that is based on dibutylboron triflate-mediated aldol reaction of suitably protected ß-amino acids bearing chiral oxazolidinone auxiliary is reported. The method smoothly afforded syn-aldol (α,ß'-syn) products in pure form and excellent isolated yield. Both α,ß-syn and α,ß-anti isomers are readily accessible solely through the choice of the oxazolidinone chirality. This method allows for the preparation of stereoisomeric ß'-hydroxy-ß-amino acid derivatives that were previously unreported.
Asunto(s)
Aldehídos/química , Aminoácidos/química , Catálisis , Técnicas Químicas Combinatorias , Ésteres/química , Estructura Molecular , EstereoisomerismoRESUMEN
Three square-planar complexes of Ni(II) with condensation derivative of 2-(diphenylphosphino)benzaldehyde and 4-phenylsemicarbazide and monodentate pseudohalides have been synthesized and characterized on the basis of the results of X-ray, NMR and IR spectroscopy and elemental analysis. Investigated complexes exhibited moderate antibacterial and cytotoxic activity. The most pronounced cytotoxic activity (in the range of cisplatin) to HeLa cell line was observed for ligand and all the complexes. Azido complex and ligand induced concentration dependent cell cycle arrest in the S phase, as well as decrease of percentage of cells in G1 phase, without significant increase of apoptotic fraction of cells. The interaction of the azido complex and ligand with CT-DNA results in changes in UV-Vis spectra typical for non-covalent bonding. The observed intrinsic binding constant of azido complex-CT-DNA and ligand-CT-DNA were 3.22 × 10(5) M(-1) and 2.79 × 10(5) M(-1). The results of DNA cleavage experiments showed that azido complex nicked supercoiled plasmid DNA.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Níquel/química , Teoría Cuántica , Amidas/química , Animales , Antineoplásicos/síntesis química , Antineoplásicos/metabolismo , Apoptosis/efectos de los fármacos , Bovinos , Ciclo Celular/efectos de los fármacos , Técnicas de Química Sintética , Complejos de Coordinación/síntesis química , Complejos de Coordinación/metabolismo , ADN/metabolismo , División del ADN/efectos de los fármacos , Estabilidad de Medicamentos , Electrones , Células HeLa , Humanos , LigandosRESUMEN
2-Picolyl azide reacts with cis-[PtCl2(DMSO)2] to form the diimino complex [Pt(II)Cl2{NHâC(H)Py}] with subsequent dinitrogen liberation. The formation of the latter complex is scrutinized in a combined experimental and theoretical analysis. We establish in silico that the transformation involves a highly reactive intermediate containing a PtâN double bond formed after the extrusion of N2 from the azide functionality. The prerequisites for N2 liberation and for the stabilization of the nitrene-related intermediate are analyzed in detail.
RESUMEN
In the title compound, C(16)H(13)NO(2), the quinoline system is approximately planar with a maximum deviation from the least-squares plane of 0.059â (1)â Å for the N atom. The phenyl ring is rotated by 62.16â (4)° with respect to the plane of the quinoline system. In the crystal, O-Hâ¯O hydrogen bonds link mol-ecules into infinite chains running along the b-axis direction.
RESUMEN
In the title compound, C(12)H(13)NO(3), the quinoline ring system is approximately planar with a maximum deviation from the least-squares plane of 0.058â (2)â Å. In the crystal, N-Hâ¯O and O-Hâ¯O hydrogen bonds link the mol-ecules into chains running along the b-axis direction. The chains also feature π-π inter-actions between pyridine and benzene rings of inversion-related mol-ecules [centroid-centroid distance = 3.609â (2)â Å].
RESUMEN
In the title hydrate, C(12)H(13)NO(4)·H(2)O, the piperidine ring that is fused to the benzene ring is in a sofa conformation with the chiral C atom lying 0.4084â (18)â Å out of the plane of the nine fused-ring atoms. In the crystal, O-Hâ¯O and N-Hâ¯O hydrogen bonds link the organic mol-ecules and water mol-ecules into chains running along the b-axis direction. The chains are further connected into layers parallel to the bc plane by π-π inter-actions between inversion-related benzene rings [centroid-centroid distance = 3.8846â (9)â Å].
RESUMEN
The complexes [(C5Me4R)TiF(µ-F)µ-O2P(OSiMe3)2]2 [R = Me (1), Et (2)] were prepared from [(C5Me4R)TiF3]2, (R = Me, Et) and OP(OSiMe3)3. The molecular structure of 2 has been determined by single-crystal X-ray diffraction analysis. An eight-membered Ti2O4P2 metallacycle bridged by two fluorine ligands between two titanium centers is observed.