On an accidental degeneracy in the 31P{¹H} NMR chemical shifts in ruthenium diphosphine complexes

The [RuCl(bipy)(dppb)(4-pic)]PF6 complex was prepared and fully characterized. The X-ray crystal structure of this complex was determined in order to make an unambiguous distinction between the two possible positions of the 4-methylpyridine ligand (4-pic) in the compound: trans to phosphorus atom or trans to nitrogen atom. The [RuCl(bipy)(dppb)(4-pic)]PF6 complex exhibits an unusual temperature-dependent accidental degeneracy of the 31P chemical shifts in its solution NMR spectrum

A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells.

Combination of multifunctionalities into one compound is a rational strategy in medicinal chemical design, and have often been used with metallodrug-based compounds. In the present study, we synthesized a novel ruthenium-based 5-fluorouracil complex [Ru(5-FU)(PPh3)2(bipy)]PF6 (PPh3?=?triphenylphosphine; and bipy?=?2,2?-bipyridine) with enhanced cytotoxicity in different cancer cells, and assessed its apoptosis induction action in human colon carcinoma HCT116 cells. The complex was characterized by infrared, cyclic voltammetry, molar conductance measurements, elemental analysis, NMR experiments and X-ray crystallographic analysis. In both 2D and 3D cell culture models, the complex presented cytotoxicity to cancer cells more potent than 5-FU. A typical morphology of apoptotic cell death, increased internucleosomal DNA fragmentation, without cell membrane permeability, loss of the mitochondrial transmembrane potential, increased phosphatidylserine externalization and caspase-3 activation were observed in complex-treated HCT116 cells. Moreover, the pre-treatment with Z-DEVD-FMK, a caspase-3 inhibitor, reduced the apoptosis induced by the complex, indicating cell death by apoptosis through caspase-dependent and mitochondrial intrinsic pathways. The complex failed to induce reactive oxygen species production and DNA intercalation. In conclusion, the novel complex displays enhanced cytotoxicity to different cancer cells, and is able to induce caspase-mediated apoptosis in HCT116 cells

Nucleobase derivatives as building blocks to borm Ru(II)-based complexes with high cytotoxicity.

Two new Ru(II)-based complexes containing 2-thiouracil derivatives, known as 2-thiouracil (2TU) and 6-methyl-2-thiouracil (6m2TU), were synthesized using cis,trans-[RuCl2(PPh3)2(bipy)] as a precursor. The obtained compounds with a general formula trans-[Ru(2TU)(PPh3)2(bipy)]PF6 (1) and trans-[Ru(6m2TU)(PPh3)2(bipy)]PF6 (2) were characterized by analytical techniques such as NMR, UV?vis, and IR spectroscopies, elementary analysis, mass spectrometry, and single-crystal X-ray diffraction. Moreover, the investigation of the complexes?DNA interaction were carried out using spectrophotometric titrations and showed that the complexes present a weak interaction with this biomolecule. The compounds were evaluated against HL-60, K-562, HepG2, and B16-F10 cancer cells and against noncancer cells (PBMCs). The results of the biological assay revealed that complex 2 is more promising than complex 1. Finally, the present study suggests that complexes 1 and 2 causes cell death by apoptosis, significantly increasing the percentage of apoptotic HL-60 cells, in which the compounds altered the cell cycle, reducing the cells in G1/G0, G2/M, and S phases

Antitumor and anti-Mycobacterium tuberculosis agents based on cationic ruthenium complexes with amino acids.

Six new complexes of Ru(II)/phenanthroline/1,4-bis(diphenylphosphino)butane containing amino acids (Glycine, L-Alanine, L-Valine, L-Tyrosine, L-Methionine or L-Tryptophan) were synthesized and characterized by IR, 31P{1H}, 13C and 1H NMR spectroscopies and cyclic voltammetry experiments. These data suggest the presence of diastereoisomers, except for the complex with glycine, amino acid that does not exhibit chiral carbon. The compounds are active against the MDA-MB-231 tumor cells and against Mycobacterium tuberculosis. The cationic ruthenium complexes with amino acids, reported here, show similar cytotoxicity against the MDA-MB-231 tumor cells. When compared with analogs complexes containing 2,20-bipyridine as ligands, instead of 1,10-phenatroline, the new complexes studied here are, in general, roughly twice more active than the 2,20-bipyridine ones and their IC50 values comparable with the cisplatin. In addition, low MICs values were obtained against Mycobacterium tuberculosis compared with the reference drugs, cycloserine and ethambutol

Novel zwitterionic oxorhenium(V) complexes: synthesis, characterization and crystal structure of [ReOX2(Hdhp)(PPh3)] (X = Cl, Br; H2dhp = 2,3-dihydroxypyridine)

Dois novos complexos zwitteriônicos de oxorrênio(V), [ReOCl2(Hdhp)(PPh3)] (1) e [ReOBr2(Hdhp)(PPh3)] (2) (H2dhp = 2,3-dihidroxipiridina), foram sintetizados e caracterizados por espectroscopia de absorção no infravermelho, ressonância magnética nuclear de ¹H e 31P, análise elementar e determinação da estrutura cristalina e molecular por difração de raios X em monocristais. Os complexos apresentam geometria de coordenação octaédrica bastante distorcida, com os dois ligantes haletos arranjados em posições cis equatoriais, o ligante trifenilfosfina em posição trans a um dos haletos e o ligante Hdhp- coordenado de forma bidentada através de seus átomos de oxigênio, sendo um em posição trans ao ligante oxo e o outro em posição trans com relação ao outro haleto. Este ligante tem seu átomo de nitrogênio protonado. Os compostos 1 e 2 apresentam empacotamento cristalino bastante diferente, influenciado em ambos os casos por ligações de hidrogênio intermoleculares dos tipos N-H...X (X = Cl, Br) e N-H...O.Two novel zwitterionic oxorhenium(V) complexes, [ReOCl2(Hdhp)(PPh3)] (1) and [ReOBr2(Hdhp)(PPh3)] (2) (H2dhp = 2,3-dihydroxypyridine), were synthesized and characterized by infrared spectroscopy, ¹H and 31P nuclear magnetic resonance, elemental analysis and crystal and molecular structure determination by X-ray diffraction on single crystals. Both complexes show distorted octahedral coordination geometry, with the halide ligands arranged in equatorial cis positions, the triphenylphosphine ligand in a trans position to one of the halides and the Hdhp- ligand coordinated in a bidentate form through its oxygen atoms, one in trans position to the oxo-ligand and the other in trans position to the second halide. The nitrogen atom of this ligand is protonated. Compounds 1 and 2 show quite different crystal packing, both influenced by hydrogen bonds of the types N-H...X (X = Cl, Br) and N-H...O

Facile synthesis and characterization of symmetric N-[(Phenylcarbonyl) carbamothioyl]benzamide thiourea : experimental and theoretical investigations.

A thiourea derivative, N-[(phenylcarbonyl)carbamothioyl]benzamide, was synthesized and characterized by elemental analysis, thermal analysis, spectroscopic methods (Fourier transform infrared (FTIR), UV-Vis, Raman, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF), tandem mass spectrometry (MS/MS) and nuclear magnetic resonance (NMR)) and quantum-chemical calculations. The synthetic route was simple and efficient, conducted just by one-step and no purification step was needed. The compound crystallizes in a non-centrosymmetric orthorhombic crystal system with a P21 21 21 space group, with a= 5.06220(10) ?, b= 11.8623(3) ?, c= 21.9682(8) ?. The molecular conformation of the solid is stabilized by the N-H???O intramolecular hydrogen bond, which was present in the X-ray structure and was also found in the optimized geometry. The theoretical analysis showed that this strong interaction remains even when molecules are solvated, i.e., the rotation barrier and the hydrogen bond strength are greater than the solvent stabilization energy. In addition to this hydrogen bond effect, the relative position of phenyl groups has a certain influence on the chemical behavior of this thiourea and probably for other phenylthioureas

Palladium(II) complexes with thiosemicarbazones: syntheses, characterization and cytotoxicity against breast cancer cells and Anti-Mycobacterium tuberculosis activity

Três complexos de PdII com tiossemicarbazonas N(4)-substituídas foram preparados: [Pd(aptsc)(PPh3)](NO3) H2O, 1, [Pd(apmtsc)(PPh3)](NO3), 2, e [Pd(apptsc)(PPh3)](NO3) H2O, 3, sendo PPh3 = trifenilfosfina; Haptsc = 2-acetilpyridina-tiossemicarbazona; Hapmtsc = 2-acetilpiridina-N(4)-metil-tiossemicarbazona e Happtsc = 2-acetilpiridina-N(4)-fenil-tiossemicarbazona. Os complexos foram caracterizados por análise elementar, IR, UV-Vis, ¹H e 31P{¹H} NMR e tiveram suas estruturas cristalinas determinadas por difratometria de raios X em monocristal. Os ligantes tiossemicarbazonatos monoaniônicos atuam de modo tridentado, ligando-se ao metal pelos átomos de nitrogênio piridínico, nitrogênio azometínico e enxofre. A atividade citotóxica frente à linhagem de células tumorais MDA-MB231 (tumor de mama) e a atividade anti-Mycobacterium tuberculosis H37Rv ATCC 27294 dos compostos foram investigadas. Os complexos de PdII mostraram-se altamente ativos contra as células tumorais, com valores de IC50 em torno de 5 µmol L-1, enquanto o agente antitumoral em uso clínico cisplatina mostrou-se inativo. Os compostos apresentaram atividade anti-M. tuberculosis significante, com valores de CIM comparáveis ou melhores que aqueles referentes a alguns fármacos usados clinicamente contra tuberculose.Three PdII complexes were prepared from N(4)-substituted thiosemicarbazones: [Pd(aptsc)(PPh3)](NO3) H2O, 1, [Pd(apmtsc)(PPh3)](NO3), 2, and [Pd(apptsc)(PPh3)](NO3) H2O, 3, where PPh3 = triphenylphosphine; Haptsc = 2-acetylpyridine-thiosemicarbazone; Hapmtsc = 2-acetylpyridine-N(4)-methyl-thiosemicarbazone and Happtsc = 2-acetylpyridine-N(4)-phenyl-thiosemicarbazone. All complexes were characterized by elemental analysis, IR, UV-Vis, ¹H and 31P{¹H} NMR spectroscopies, and had their crystalline structures determined by X-ray diffractometry from single crystals. The monoanionic thiosemicarbazonate ligands act in a tridentate mode, binding to the metal through the pyridine nitrogen, the azomethine nitrogen and the sulfur atoms. The cytotoxic activity against the breast cancer cell line MDA-MB231 and the anti-Mycobacterium tuberculosis H37Rv ATCC 27294 activity were evaluated for the compounds. All PdII complexes were highly active against the studied cell line, presenting similar values of IC50, around 5 µmol L-1, while the clinically applied antitumor agent cisplatin was inactive. The compounds show remarkable anti-M. tuberculosis activities, presenting MIC values comparable or better than some commercial anti-M tuberculosis drugs

Reactive nitrogen/oxygen species production by nitro/nitrosyl supramolecular ruthenium porphyrin complexes.

This manuscript reports on new nitro/nitrosyl Ru-based complexes, which were synthesized with the purpose of using them as precursors to obtain supramolecular ruthenium porphyrin species ({TPyP[Ru (NO2)(5,50-Mebipy)2]4}(PF6)4) and ({TPyP[Ru(NO)(5,50-Mebipy)2]4}(PF6)12). The photochemical and photophysical properties of these porphyrin species were investigated. Results show that the complex containing nitrite is able to produce NO by homolytic O?NO cleavage (FPPh NO = 0.05) while the {TPyP[Ru (NO)(5,50-Mebipy)2]4}(PF6)12 does it by direct labilization (FPPh NO = 0.53) of the Ru NO bond. Furthermore, a triplet quantum yield of 0.09 and 0.27 was observed for complexes containing nitrite and nitric oxide, respectively. The reactive oxygen species quantum yield for the complex {TPyP[Ru(NO) (5,50-Mebipy)2]4}(PF6)12 (0.78) is consistent with the sum of quantum yields NO release (0.53) and triplet state (0.27), which suggests that both processes participate in the formation of the reactive species. Our results show that combining these characteristics, NO production and triplet states, on the same platform could induce a synergic effect, leading to a considerable improvement in the photodynamic action of these complexes