This work reports the synthesis, structure and catalytic activity of a novel ruthenium(II) complex, [RuCl(dppb)(44bipy)(4-pic)]PF6 (where dppb = 1,4-bis(diphenylphosphine)butane; 44bipy = 4,4’-dimethyl-2,2’-dipyridyl; 4-pic = 4-picoline). The molecular structure and catalytic activity were studied by Fourier transform infrared (FTIR), UV-Vis and nuclear magnetic resonance (NMR) spectroscopies, cyclic voltammetry, and X-ray crystallography, while the electronic structure was investigated by density-functional theory (DFT) and time dependent DFT (TD-DFT) methods. Electrochemical studies showed the substitution of the chlorido ligand from the precursor by the 4-pic ligand, exhibiting the RuII/RuIII process at 1.21 V. The structure of the compound was optimized using DFT simulations and showed data similar to the X-ray structure. The UV-Vis absorption spectrum showed a good agreement with TD-DFT simulations. The highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies were determined at the Becke, 3-parameter, Lee-Yang-Parr (B3LYP) level. The study of the catalytic activity in the transfer hydrogenation of ketones by the 1H NMR showed efficient transfer hydrogenation reaction at 60 ºC, employing acetophenone as substrate and resulting in a high conversion. The formation of two ruthenium-hydride species was observed.

Mononuclear and binuclear RuII/arene/triphenylphosphine complexes with p-substituted benzoic acid derivatives were prepared and characterized. These monocationic complexes of type [Ru(η6-p-cymene)(PPh3)L] (L = benzoic acid (1), p-hydroxybenzoic acid (2), p-nitrobenzoic acid (3) and terephthalic acid (4)) were characterized using various techniques, such as nuclear magnetic resonance (NMR) and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry, and the crystal structure of 1, 3 and 4 were determined by X-ray diffraction analysis. The cytotoxicity of the complexes was evaluated, in vitro, against tumorigenic [MDA-MB-231, MCF-7 (breast), A549 (lung) and DU-145 (prostate)] and non-tumorigenic [MCF-10A (breast), MRC-5 (lung) and PNT-2 (prostate)] cells. The binuclear complex (4) was inactive due to its low solubility. Complexes 1, 2 and 3 showed similar cytotoxicity, however, complex 1 presented better selectivity index against MDA-MB-231 than compounds 2 and 3. Cellular ruthenium absorption was explored by inductively coupled plasma mass spectrometry (ICP-MS) analyzing the whole cells and the culture medium. Complementary studies showed that complex 1 inhibited colony formation, induced morphology changes in cells and promoted cell cycle arrest in the Sub-G1 phase for the MDA-MB-231 cells.

The preparation, characterization, theoretical calculations and biological application of four RuII complexes with 2-picolinate (pic), 2,2’-bipyridine (bipy) and P-P as ligands [P-P = 1,1-bis(diphenylphosphino)methane (dppm-1), 1,2-bis(diphenylphosphino)ethane (dppe-2), 1,3-bis(diphenylphosphino)propane (dppp-3) or 1,1’-bis(diphenylphosphino)ferrocene (dppf-4)], is here presented. The complexes 1-4, with general formula [Ru(pic)(P-P)(bipy)]PF6, were characterized by elemental analysis and by infrared (IR), UV-Vis, nuclear magnetic resonance (NMR 1H and 13P{1H}) spectroscopies, cyclic voltammetry and X-ray crystallography technique. Additionally, preliminary in vitro tests against human breast (MDA-MB-231) and murine ascitic sarcoma 180 (S180) tumor cell lines were carried out, and compared with cisplatin, a reference drug. The drug concentration at which 50% of the cells are viable relative to the control (IC50) values found for complexes 1, 2, 3 and 4 against MDA-MB-231 tumor cells were around 14.6, 7.6, 3.3 and 0.4 µM, respectively, while against S180 tumor cells these complexes showed IC50 values of 71.9, 31.3, 11.2 and 3.5 µM, respectively. Therefore, the complexes were more active against MDA-MB-231 than S180.

Herein we present four new ruthenium(II) complexes: [Ru(mtz)2(dppb)] (1), [Ru(mmi)2(dppb)] (2), [Ru(dmp)2(dppb)] (3), and [Ru(mpca)2(dppb)] (4), where mtz = 2-mercaptothiazoline; mmi = 2-mercapto-1-methyl-imidazole; dmp = 4,6-diamino-2-mercaptopyrimidine; mpca = 6-mercaptopyridine-3-carboxylic acid; dppb = 1,4-bis(diphenylphosphino)butane. In vitro cell culture experiments revealed cytotoxic activity for complexes 2, 3 and 4 against MCF-7 (breast, non-invasive), MDA-MB-231 (breast, invasive), A549 (lung), DU-145 (prostate) and HepG2 (liver) tumor cells, in some cases lower than the half maximal inhibitory concentration (IC50) for the reference drug (cisplatin). The deoxyribonucleic acid (DNA) interactions studied by viscosity measurements, gel electrophoresis and square-wave voltammetry indicated that the DNA binding affinity primarily occurs through non-covalent interactions. Only complex 2 was able to fully inhibit the DNA supercoiled relaxation mediated by human topoisomerase IB (Top IB). The analysis indicates that complex 2 inhibits the cleavage and the reconnection steps of the catalytic cycle, being both a poison and a catalytic inhibitor.

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) Å, b= 11.8623(3) Å, c= 21.9682(8) Å. 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.

The syntheses, characterization, cytotoxicity against tumor cells and anti-Mycobacterium tuberculosis activity assays of PtII/PPh3/N,N-disubstituted-N'-acylthioureas complexes with general formulae [Pt(PPh3)2(L)]PF6, PPh3 = triphenylphosphine; L = N,N-disubstituted-N'-acylthiourea, are here reported. The complexes were characterized by elemental analysis, molar conductivity, infrared (IR), nuclear magnetic resonance (NMR) (1H, 13C{1H} and 31P{1H}) spectroscopy. The 31P{1H} NMR data are consistent with the presence of two PPh3 ligands cis to each other position, and one N,N-disubstituted-N'-acylthiourea coordinated to the metal through O and S, in a chelate form. The structures of the complexes were determined by X-ray crystallography, forming distorted square-planar structures. The complexes were tested in human cell lines carcinomas and also screened with respect to their anti-Mycobacterium tuberculosis activity (H37RvATCC 27294). It was found that complexes with N,N-disubstituted-N'-acylthiourea containing open and small chains as R2 groups show higher cytotoxic and higher anti-Mycobacterium tuberculosis activity than those containing rings in this position.

This paper describes a new series of four DNA-intercalating agents with promising anticancer activities, based on ruthenium(II) with the planar ligand dpqQX (dpqQX = dipyrido[3,2-a:2',3'-c]quinoxaline[2,3-b]quinoxaline). The complexes identified as trans-[RuCl2(dppb)(dpqQX)], cis-[RuCl2(dppb)(dpqQX)], ct-[RuCl(CO)(dppb)(dpqQX)]PF6 and ct-[RuCl2(PPh3)2(dpqQX)] (dppb = 1,4-bis(diphenylphosphine)butane and PPh3 = triphenylphosphine) were characterized by 31P{1H} nuclear magnetic resonance (NMR) and infrared spectroscopies, cyclic voltammetry, molar conductance measurements, elemental analysis, mass spectrometry and X-ray diffraction analysis for complex ct-[RuCl2(PPh3)2(dpqQX)]. Their in vitro cytotoxic activities against MDA-MB-213 and MCF-7 breast cancer cells were evaluated and compared with normal L-929 cells. Low drug concentration at which 50% of the cells are viable relative to the control (IC50) values were obtained for all four complexes compared with a reference metallodrug, cisplatin. In addition, DNA affinity studies from titrations, as well as the images obtained by atomic force microscopy (AFM) involving pBR322 plasmid DNA, suggest interactions between the metal complexes and the DNA macromolecule, in which they act as intercalating agents. The intercalation of the complexes with DNA was confirmed by viscosity measurements.

The [Ru(Spym)(bipy)(P–P)]PF6, [Spym = pyrimidine-2-thiolate anion; P–P = 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)propane and 1,1'-bis(diphenylphosphino)ferrocene] complexes were synthesized and characterized by spectroscopic, electrochemical and elemental analysis, and by X-ray crystallography. The minimal inhibitory concentration (MIC) of the compounds against Mycobacterium tuberculosis and the complex concentration causing 50% tumor cell growth inhibition (IC50) against breast cancer cells, MDA-MB-231, were determined. All three compounds gave promising values in both tests. It is interesting to mention that all three complexes display MICs against Mycobacteriumtuberculosis showing higher activity than cycloserine, a second line drug used in the treatment of the illness. The complexes interact weakly with the DNA.

The synthesis, characterization and cytotoxic activity of cis-[Ru(dicl)(dppm)2]PF6 and cis-[Ru(ibu)(dppm)2]PF6, (dppm = 1,1-bis(diphenylphosphine)methane; dicl = diclofenac anion and ibu = ibuprofen anion), are described in this work. Complexes were characterized by elemental analysis, Fourier transform infrared spectroscopy (FTIR), UV-Vis, 31P{1H} nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRESIMS). X-ray structure of cis-[Ru(ibu)(dppm)2]PF6 is also described. Preliminary calf thymus DNA (ct-DNA) binding studies were carried out by UV-Vis and viscosity experiments, with results suggesting the existence of electrostatic interactions between ruthenium complexes and ct-DNA. Cytotoxicity assays were carried out on a panel of human cancer cell lines and a human normal cell line. Complexes displayed a high to moderate cytotoxicity with IC50 ranging from 5 to 47 µmol L-1. cis-[Ru(ibu) (dppm)2]PF6 was found to be the most active, with IC50 values lower than cisplatin. The degree of cytotoxicity was maintained for the normal cell line, although cis-[Ru(ibu)(dppm)2]PF6 exhibited a similar selectivity to that of cisplatin but with a higher activity for at least two tumor cell lines which evidences a promising anticancer candidate and selects this complex for further experiments.

A porfirina 5,10,15,20-Tetra(4-piridil)manganês(III), [Mn-TPyP(H2O)2]PF6, e a porfirina supramolecular eletropolimerizável (ESP), {Mn-TPyP(H2O)2[RuCl3(dppb)]4}PF6 (dppb = 1,4-bis(difenilfosfina)butano), foram sintetizadas e caracterizadas. Um filme fino da PSE foi obtido na superfície do eletrodo de carbono vítreo utilizando o método de voltametria cíclica. Foi observado um aumento da corrente de pico com o aumento do número de ciclos voltamétricos, mostrando um comportamento típico de espécies sendo adsorvidas na superfície do eletrodo. O eletrodo modificado com a ESP foi utilizado para a quantificação de acetoaminofeno por voltametria cíclica. O eletrodo modificado apresentou resposta linear de corrente de pico anódico em função da concentração de acetoaminofeno na faixa de concentração entre 0,05 e 0,70 mmol L- 1. O eletrodo modificado foi utilizado para a determinação de acetoaminofeno em uma amostra comercial e os resultados foram satisfatórios, pois apresentaram concordância quando comparado pelo método de HPLC.

Porphyrin 5,10,15,20-Tetra(4-pyridyl)manganese(III), [Mn-TPyP(H2O)2]PF6, and electropolymerized supramolecular porphyrins (ESP), {Mn-TPyP(H2O)2[RuCl3(dppb)]4}PF6 (dppb = 1,4-bis(diphenilphosphine)butane), were synthesized and characterized. A thin solid film of ESP was obtained on a glass carbon electrode surface by a cyclic voltammetry method. The peak current increased with the number of voltammetric cycles, which shows a typical behavior of the species being adsorbed on the surface of the electrode. Cyclic voltammetry was also employed for acetaminophen quantification using an ESP modified electrode. The modified electrode shows a linear relationship between the anodic peak current and the concentration of acetaminophen (in the rage 0.05 to 0.7 mmol L- 1). The performance of the modified electrode was verified by the determination of acetaminophen in a commercial pharmaceutical product and the results were in good agreement with those obtained by a control HPLC method.

As reações de substituição [RuCl2(P-P)(N-N)] + L → [RuCl(L)(P-P)(N-N)]+ + Cl-, onde P-P = 1,4-bis(difenilfosfino)butano e N-N = 2,2´-bipiridina, 4,4´-dimetóxi-2,2´-bipiridina, 4,4´-dimetil-2,2´-bipiridina e 4,4´-dicloro-2,2´-bipiridina, L = piridina (py) ou 4-metilpiridina (4-pic), foram estudadas sob condições de pseudo-primeira ordem. As reações ocorrem por um mecanismo dissociativo e as constantes de velocidade nas reações de substituição aumentam com o aumento do pKa dos ligantes N-heterocíclicos e com a diminuição dos potenciais de oxidação do centro metálico. Quanto mais alta é a porcentagem de participação dos orbitais atômicos d do metal na formação do HOMO, conforme calculado pelo método DFT, mais fácil é a dissociação do cloreto da esfera de coordenação do complexo. Nos espectros de 31P{¹H} RMN da série de complexos de fórmula geral [RuCl(L)(P-P)(N-N)]PF6, há dois dubletos com Δσ < 1, o que é consistente com produtos formados pela dissociação do cloreto trans ao átomo de fósforo nos precursores.

The substitution reactions [RuCl2(P-P)(N-N)] + L → [RuCl(L)(P-P)(N-N)]+ + Cl-, where P-P = 1,4-bis(diphenylphosphino)butane and N-N = 2,2´-bipyridine, 4,4´-dimethoxy-2,2´-bipyridine, 4,4´-dimethylpyridine-2,2´-bipyridine and 4,4´-dichloro-2,2´-bipyridine, L = pyridine (py) or 4-methylpyridine (4-pic), were studied under pseudo-first order conditions. The reactions proceeded by means of a dissociative mechanism. The rate constants of the substitution reactions increased as the pKa of the N-heterocyclic ligands increased and as the oxidation potential of the metal center decreased. The greater the participation of the atomic d orbitals of the metal in the HOMO, according to DFT calculations, the easier is the dissociation of the chloride from the coordination sphere of the complex. In the 31P{¹H} NMR spectra of the series of complexes of general formula [RuCl(L)(P-P)(N-N)]PF6, there are two doublets with Δσ < 1. This is consistent with products formed by dissociation of the chloride trans to one of the phosphorus atoms in the precursors.

Um novo derivado da piperazina, 5-oxopiperazinio-3-sulfonato monohidratado, foi produzido a partir de uma rota sintética simples como resultado da adição do íon bisulfito, HSO3-, ao anel e do ataque nucleofílico de moléculas de água a moléculas de pirazina. O material isolado foi caracterizado por RMN, espectrometria de massa, infravermelho e difração de raios-X.

A new derivative of piperazine, 5-oxopiperazinium-3-sulfonate monohydrate, was produced from a simple synthetic route as a result of the nucleophilic addition to HSO3- bisulphite ion and of the nucleophilic attack of water molecules on pyrazine molecules. The isolated material was characterized by means of NMR, mass spectrometry, infrared, and X-ray diffraction.

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.

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.

Modificações no sinal de absorção de estado excitado da 5,10,15,20-tetra(4-piridil)-21H,23H-porfirina, provocadas tanto pela substituição do íon central quanto pela adição de grupos periféricos, são investigadas empregando-se pulsos laser de 5 ns com 532 nm, juntamente com medidas de absorção linear e tempo de decaimento da fluorescência. A absorção saturada reversa (RSA) aumenta consideravelmente quando os íons H+ são substituídos pelo Zn2+ na posição central do anel porfirínico. Contudo, esta diminui quando os grupos RuCl2(CO)(PPh3)2 e RuCl2(CO)(dppb) são ligados através dos anéis piridínicos às posições periféricas da porfirina, tanto para a base livre quanto para a zinco porfirina. Um modelo teórico baseado no diagrama de Jablonski foi usado para verificar qual a principal causa da diminuição do sinal de RSA provocada pelos grupos de rutênio.

Investigations on the excited state absorption signal of 5,10,15,20-tetra(4-pyridyl)-21H,23H-porphyrin, modified by either changing the central ion or adding peripheral groups, were performed using 5 ns laser pulses at 532 nm, in association with linear absorbance and fluorescence decay time measurements. The reverse saturable absorption (RSA) increases remarkably when Zn2+ replaces H+ at the central position of the porphyrin ring. However, it decreases when RuCl2(CO)(PPh3)2 and RuCl2(CO)(dppb) groups are attached at outlying positions through the pyridine rings, for both the free base and zinc porphyrins. A theoretical model based on Jablonski diagram was used to verify the main reason for the decrease on the RSA signal caused by ruthenium groups.