Multi-drug-resistant bacteria (MDR) are the cause of different infections and diseases that have affected humanity for a long time, and have been an emerging global health problem that has led to increased morbidity and mortality. The growing emergence of MDR bacteria has underlined the need for development and discovery of new antibacterial compounds. In this context, a series of new paeonol 1,2,3-triazole and ether derivatives were synthesized using copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and nucleophilic substitution. Paeonol has been a natural product widely studied due to its many biological activities, as well as its derivatives. Three ether derivatives (two unpublished) and ten triazole derivatives (six unpublished) of paeonol were obtained, which were determined by nuclear magnetic resonance (NMR), Fourier transform infrared spectrometry (FTIR), Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and six of them by X-rays, which is the first study of this type presented for these compounds. All the synthesized compounds were evaluated as antibacterial agents against Staphylococcus aureus and Escherichia coli, obtaining a minimum inhibitory concentration (MIC) above 100 µg mL-1. The results showed that CuAAC and nucleophilic substitution were very useful to obtain new paeonol triazole and ether derivatives and the products were obtained in yields from 21.3 to 98.5%. The advantages of these reactions (high yield in most compounds, reaction time, low impurities) show that using the method to produce new derivatives is advisable thus assisting in the discovery of new potential bioactive compounds.

Two series of allyl sulfonamides, prepared from Morita-Baylis-Hillman adducts and primary aromatic sulfonamides, were fully characterized. The Z configuration for the products derived from 2-[hydroxy(phenyl)methyl]acrylonitrile (1) and E configuration for those derived from methyl 2-[hydroxy(phenyl)methyl]acrylate (2) were confirmed by X-ray diffraction for one compound of each series (1e, 2f). Density functional theory calculations for all allyl sulfonamides agreed with the X-ray crystallographic data. X-ray diffraction studies indicate that these compounds form dimers in their crystal structures. Fingerprint plots show that compound 1e is stabilized by H⋯H, C⋯H/H⋯C, O⋯H/H⋯O and N⋯H/H⋯N interactions, while the compound 2f has no N⋯H/H⋯N contacts. Hirshfeld surface analyses were performed to gain insight into the behavior of these interactions. Calculated frontier orbitals showed that their highest occupied and lowest unoccupied molecular orbitals are antibonding orbitals. The allyl sulfonamides 1e and 2f are among the most active compounds in each series, inhibiting approximately 60% of the mycelial growth of Botrytiscinerea at 3 mmol L-1.

Resumen La estructura cristalina del compuesto ácido 2-E-((4-hidroxifenil) diazenil) benzoico se resolvió por medio del método de fase intrínseca usando datos de difracción de rayos X de monocristal, encontrando que la molécula cristaliza en el sistema cristalino ortorrómbico con grupo espacial Pbca. Dentro de su celda unidad hay cuatro moléculas por unidad asimétrica que son confórmeros moleculares. Estos confórmeros forman hélices beta a lo largo de la dirección [010]. A partir de los datos estructurales se realizó el cálculo de superficies de Hirshfeld determinando, a partir de ellas, sus correspondientes diagramas de huellas dactilares bidimensionales, lo que permitió estudiar las interacciones intermoleculares que más contribuyen al empaquetamiento cristalino. Así, se pudo determinar que la principal contribución a la superficie general está dada por los contactos H•••H (34,8%), seguida de interacciones O•••H/ H•••O (27%) y C•••H/H•••C (18,6%). También fueron calculadas las redes energéticas de interacción con un nivel de teoría DFT/B3LYP/6-31G(d,p), permitiendo cuantificar los valores de cada componente que aportan a la energía total, siendo las interacciones de dispersión (-57,5 kJ/mol) las que más contribuyen en la formación del empaquetamiento cristalino para este compuesto.

Abstract The crystalline structure of 2-E-((4-hydroxyphenyl) diazenil) benzoic acid compound was solved by intrinsic phase method using single-crystal X-ray diffraction data. The molecule crystallizes in the orthorhombic Pbca space group. in the unit cell four molecular conformers of the compound per asymmetric unit are observed, which are forming beta helix arrangement along [010] direction. Hirshfeld surface calculation was performed to determine the intermolecular interactions that contribute to the crystal packing. it was possible to observe that the main contribution to the general surface is given by the contacts H ••• H (34.8%), followed by interactions O ••• H/H ••• O (27%) and C ••• H/H ••• C (18.6%). The energy interaction networks were calculated at a DFT/B3LYP/6-31G(d,p) level, allowing to quantify the high participation of dispersion interactions (-57.5 kJ/mol) in the formation of crystal packing.

Resumo A estrutura cristalina do composto ácido 2-E-((4-hidroxifenil) diazenil) benzóico foi resolvida pelo método da fase intrínseca usando dados de difração de raios X de cristal único, constatando que a molécula cristaliza no sistema cristalino ortorrômbico com grupo espacial Pbca. Dentro de sua cela unitária, existem quatro moléculas por unidade assimétrica, que são isômeros moleculares. Esses isômeros formam hélices beta na direção [010]. A partir dos dados estruturais, foi realizado o cálculo das superfícies de Hirshfeld determinando a partir delas seus respetivos diagramas bidimensionais das impressões digitais, o que permitiu estudar as interações intermoleculares que mais contribuem para o empacotamento cristalino. Assim, foi determinado que a principal contribuição para a superfície geral é dada pelos contatos H ••• H (34,8%), seguidos pelas interações O ••• H / H••• O (27%) e C ••• H / H ••• C (18,6%). Também foram calculadas as redes de energia de interação com um nível de teoria DFT/B3LYP/6-31G(d,p), permitindo quantificar a alta participação de interações de dispersão (-57,5 kJ / mol) na formação do empacotamento cristalino para este composto.

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.

Twelve tetraphenylphosphonium allyldithiocarbimates were synthesized and fully characterized by high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), infrared and nuclear magnetic resonance (NMR) spectroscopies. The spectroscopic data indicated that the allyldithiocarbimate anions present Z configuration, as confirmed by X-ray crystallography. These new compounds inhibited the germination of Phakopsora pachyrhizi and Hemileia vastatrix at very low doses, with IC50 (concentration to achieve 50% of inhibition of spore germination) values ranging from 0.028 to 0.166 mmol L-1, and IC90 (concentration to achieve 90% of inhibition of spore germination) values varying from 0.156 to 0.528 mmol L-1. Allyldithiocarbimate salts are lead compounds for the development of new antifungals for coffee leaf rust and Asian soybean rust, devastating plant diseases with limited control options.

A combined phytochemical, crystallographic and biological study of Worsleya procera roots was performed. Fifteen alkaloids were identified by gas chromatography mass spectrometry (GC-MS) and seven of them were isolated. The structures of the alkaloids were elucidated by spectroscopic methods, and a detailed crystallographic study of tazettine was carried out. The isolated alkaloids and the obtained extracts were tested in vitro against Plasmodium falciparum (3D7 and K1 strains) and human hepatocarcinoma cells (HepG2) to assess their antiplasmodial and cytotoxic effects, respectively. One of the isolated alkaloid derivatives, lycorine, exhibited antiplasmodial activity against both sensitive (3D7) and resistant (K1) parasite strains in the low micromolar range (half-maximal sample inhibitory concentration (IC50) values of 2.5 and 3.1 µM, respectively) and displayed a low cytotoxicity profile, with a selectivity index greater than 100. Our findings indicate that lycorine is a hit for antimalarial drug discovery.

Herein, we present the serendipitous obtaining of 7-chloro-2,3-dihydro-5H-thiazolo [3,2-a]pyrimidin-5-one in 40% yield by using POCl3 and a thiobarbituric acid derivative. The thiazolopyrimidine derivative was characterized by 1H nuclear magnetic resonance (NMR), UV-Vis, and Fourier transform infrared (FTIR) spectroscopy. Additionally, the structure was confirmed by single crystal X-ray diffraction, where it was found that the compound crystallizes in the P-1 triclinic space group with two conformeric molecules of 7-chloro-2,3-dihydro-5H-thiazolo [3,2-a] pyrimidin-5-one by asymmetric unit. Also, from the structural data was studied the supramolecular interactions using Hirshfeld surface analysis and 2D fingerprint plots.

Lots of Educational Institutions hold their own geocollection due to its utility and versatileness in the practical formation of new generations of skillful professionals in many areas of Science and Technology. The Geoscience laboratory of the Federal University of São Carlos has a collection of minerals used in engineering, mineralogy and other technological courses ministered to undergraduates of different programs. Three samples of this collection were identified using Raman spectroscopy. The analysis carried out in this work enabled the characterization of the major mineral components in the samples as well as the identification of other minor crystalline phases present in the sample. It is important to notice that this information could not be obtained using the regular analyses of mineral properties, such as density, streak, hardness, brightness, cleavage, among others. As a result, the samples A170801 and A170802 were characterized as being mainly calcite (CaCO3) and spodumene (LiAlSi2O6), respectively. On the other hand, sample A170803 show the presence of three different minerals: graphite (C), quartz (SiO2) and muscovite [KAl2(Si3Al)O10(OH,F)2].

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 cis-[Ru(bpy)2(4-bzpy)(NO)](PF6)3 complex was prepared (4-bzpy = 4-benzoylpyridine), and characterized by UV-visible, infrared and nuclear magnetic resonance (NMR) spectroscopies and electrochemical techniques. The reaction with cysteine was preliminarily investigated, aiming to shed light on the potential biological mechanism for NO or HNO release mediated by thiols. Furthermore, photochemical behavior of cis-[Ru(bpy)2(4-bzpy)(NO)](PF6)3 was studied, where it was observed NO release upon ultraviolet, blue and green light irradiations. This latter long wavelength showed still good efficiency, which has not been reported for this type of complex. This feature is very important for a potential application in phototherapy. Additionally, vasorelaxant activity was investigated in rat-isolated aorta. This compound exhibited a greater maximum efficacy than sodium nitroprusside (SNP) as a blood vessel relaxant. Nevertheless, the EC50 for SNP (13.3 nmol L-1) was 52-fold smaller than the EC50 for cis-[Ru(bpy)2(4-bzpy)NO](PF6)3 (690 nmol L-1). Altogether, these results suggest this complex is a promising NO donor agent deserving further biological studies.

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.

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.

This article describes the synthesis of the new (2Z)-2-(4-methoxybenzylidene)-6-nitro-4H -benzo[1,4]thiazin-3-one, (2Z)-2-(4-methoxybenzylidene)-4-methyl-6-nitro-4H-benzo[1,4]thiazin-3-one, (2Z)-6-amino-2-(4-methoxybenzylidene)-4H -benzo[1,4]thiazin-3-one, (2Z)-6-butylamino-2-(4-methoxybenzylidene)-4-methyl-4H-benzo[1,4]-thiazin-3-one and (2E)-N-alkyl-N-(2-hydroxy-5-nitrophenyl)-3-phenylacrylamides and the spectroscopic data. The arylidenebenzothiazine compounds were prepared using the Knoevenagel condensation with substituted benzaldehydes in the presence of sodium methoxide in DMF. The presence of a nitro substituent in the 4-position, water and a slightly acid reaction medium in this condensation caused the rupture of the benzothiazine ring and subsequent formation of the phenylacrylamide compounds. A crystallographic data was presented for (2E)-3-(4-bromophenyl)-N-dodecyl-N -(2-hydroxy-5-nitrophenyl) acrylamide.