Biheterocyclic ligands: synthesis, characterization and coordinating properties of bis(4-amino-5-mercapto-1,2,4-triazol-3-yl) alkanes with transition metal ions and their thermokinetic and biological studies

The Co(II), Ni(II) and Cu(II) metal ions complexes of Bis(4-amino-5-mercapto-1,2,4-triazol-3-yl) alkanes (BATs) have been prepared and characterized by elemental analysis, conductivity measurements infrared, magnetic susceptibility, the electronic spectral data and thermal studies. Based on spectral and magnetic results, the ligands are tetradentate coordinating through the N and S-atoms of BATs; six-coordinated octahedral or distorted octahedral and some times four-coordinated square planar were proposed for these complexes. Activation energies computed for the thermal decomposition steps were compared. The ligands and their metal complexes were tested in vitro for their biological effects. Their activities against two gram-positive, two gram-negative bacteria and two fungal species were found to vary from moderate to very strong.

Electrochemical properties of Cu4[PhN3C6H4N3(H)Ph]4(µ-O)2, a tetranuclear Copper(II) complex with 1-phenyltriazenido-2-phenyltriazene-benzene as ligand

Bis-(µ2-oxo)-tetrakis{[1-feniltriazene-1,3-diil)-2-(phenyltriazenil)benzene copper(II) is a tetranuclear complex which shows four Cu(II) ions coordinated by four 1,2-bis(phenyltriazene)benzene bridged ligands, with one diazoaminic deprotonated chain, and two O2- ligands. The complex reduces at E1/2 = -0.95 V vs Fc+/Fc, a two electrons process. Cyclic voltammetric and spectroelectrochemical studies showed a reversible process. When immobilized on carbon paste electrode, the complex electrocatalyses the reduction of O2 dissolved on aqueous solution at -0.3 V vs SCE potential. The obtained current shows linearity with O2 concentration.

Highly sensitive spectrophotometric methods for the determination of olanzapine

Highly sensitive and selective spectrophotometric methods (A and B) were developed for the determination of micro amounts of olanzapine (OLZ). Method A (direct method) is based on the oxidation of olanzapine with a known excess of iodine monochloride (ICl) in an acidic medium. Under the same condition, thymol blue was iodinated by unreacted ICl, and the absorbance of uniodinated thymol blue was measured at 536 nm. The decrease in ICl concentration is a measure of drug concentration. In method B (indirect method), oxidation of OLZ by a known excess of Ce(IV) in sulfuric acid medium followed by the reaction of unreacted Ce(IV) with leuco crystal violet (LCV) to crystal violet (CV), which is measured in an acetate buffer medium ( pH 4.9) at 580 nm. These methods obey the Beer's law in the concentration range of 0.2-1.6 µg mL-1 (method A) and 0.1-1.4 µg mL-1 (method B). The developed procedures have been successfully applied to the determination of OLZ in pure and in dosage forms. The results exhibit no interference from the presence of excipients. The reliability of the methods was established by parallel determination of OLZ against the reference method.

Anacardic acid derivatives from Brazilian propolis and their antibacterial activity

Propolis is a sticky, gummy, resinous substance collected by honeybees (Apis mellifera L.) from various plant sources, which has excellent medicinal properties. This paper describes the isolation and identification of triterpenoids and anacardic acid derivatives from Brazilian propolis and their antibacterial activity. Their structures were elucidated by ¹H and 13C NMR, including uni- and bidimensional techniques; in addition, comparisons were made with data from academic literature. These compounds were identified as: cardanols (1a + 1b), cardols (2a + 2b), monoene anacardic acid (3), a-amirine (4), b-amirine (5), cycloartenol (6), 24-methylene-cycloartenol (7) and lupeol (8). The determination of the position of the double bond after a reaction with Dimethyl disulfide (DMDS) is described for the phenol derivatives. The ethanolic extract was tested in vitro for antimicrobial activity by using the disc diffusion method and it showed significant results against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Shigella spp.

Polarographic study and electrode kinetics of [Zn(II) - antibiotics - cephaloglycin] system vis a vis kinetics of electrode reactions

Electrode kinetics and complex formation of Zn(II) using doxycycline, chlortetracycline, oxytetracycline, tetracycline, minocycline, amoxicillin, chloramphenicol and cephaloglycin were reported at pH = 7.30 ± 0.01 in = 1.0 molL-1 NaClO4 used as supporting electrolyte at 25.0°C. Kinetic parameters viz. transfer coefficient (α), degree of irreversibility (λ) and rate constant (k) were determined. The study showed that 'Transition state' behaves between reactant (O) and product (R) response to applied potential. The stability constants varied from 2.14 to 10.31 showing that these drugs or their complexes could be used against Zn toxicity.

Evaluation of group electronegativities and hardness (softness) of group 14 elements and containing functional groups through density functional theory and correlation with NMR spectra data

Quantum Chemical calculations for group 14 elements of Periodic Table (C, Si, Ge, Sn, Pb) and their functional groups have been carried out using Density Functional Theory (DFT) based reactivity descriptors such as group electronegativities, hardness and softness. DFT calculations were performed for a large series of tetracoordinated Sn compounds of the CH3SnRR'X type, where X is a halogen and R and R' are alkyl, halogenated alkyl, alkoxy, or alkyl thio groups. The results were interpreted in terms of calculated electronegativity and hardness of the SnRR'X groups, applying a methodology previously developed by Geerlings and coworkers (J. Phys. Chem. 1993, 97, 1826). These calculations allowed to see the regularities concerning the influence of the nature of organic groups RR' and inorganic group X on electronegativities and hardness of the SnRR'X groups; in this case, it was found a very good correlation between the electronegativity of the fragment and experimental 119Sn chemical shifts, a property that sensitively reflects the change in the valence electronic structure of molecules. This work was complemented with the study of some compounds of the EX and ER types, where E= C, Si, Ge, Sn and R= CH3, H, which was performed to study the influence that the central atom has on the electronegativity and hardness of molecules, or whether these properties are mainly affected for the type of ligand bound to the central atom. All these calculations were performed using the B3PW91 functional together with the 6-311++G** basis set level for H, C, Si, Ge, F, Cl and Br atoms and the 3-21G for Sn and I atoms.

Determination of atenolol in pharmaceutical formulations by diffuse reflectance spectroscopy

A simple analytical method for quantification of atenolol in pharmaceutical formulations by diffuse reflectance spectroscopy is described. The method is based on the reaction, on the filter paper surface, between the drug and p-chloranil producing a colored compound. The best reaction conditions were obtained with 20 µL of atenolol solution and 20 µL of p-chloranil. All reflectance measurements were carried out at 550 nm and the linear range was from 1.13x10-2 to 7.88x10-2 mol L-1 (r = 0.9992). The limit of detection was 2.80 x 10-3 mol L-1. The proposed method was successfully applied to analysis of different commercial brands of pharmaceutical formulations and the results obtained by the proposed method were in good agreement with those obtained using the British Pharmacopoeia method.

Dinâmica molecular: teoria e aplicações em planejamento de fármacos

Dinâmica Molecular (DM) é uma ferramenta computacional poderosa usada em Química Medicinal para o planejamento racional de fármacos. DM é uma extensão da Mecânica Molecular, onde o comportamento dinâmico de um sistema molecular é simulado através da integração numérica das equações de movimento. Esta técnica tem sido usada extensivamente para auxiliar e complementar o planejamento de novos ligantes de um alvo terapêutico, bem como estimar a sua potência. Este artigo enfoca a teoria básica da DM clássica e suas importantes aplicações no planejamento racional de potenciais compostos bioativos, particularmente compostos com atividade anti-HIV.

Otimização multivariada e aplicação do sorvente SiO2-Nb2O5 para determinação em linha de Ni(II) em matriz aquosa

Neste estudo foi desenvolvido uma metodologia para determinação de Ni(II) em amostras de água usando a extração em fase sólida (SPE) em um sistema por injeção em fluxo (FI) e detecção por espectrometria de absorção atômica em chama (F AAS). O adsorvente utilizado para a extração e pré-concentração do Ni(II) foi a sílica gel modificada com óxido de nióbio(V). Variáveis químicas e de fluxo do sistema em linha foram otimizadas usando planejamento fatorial completo (N = 2k + 3). As condições iniciais do sistema FI-F AAS foram volume de amostra de 10 mL e concentração de Ni(II) de 100 µg L-1. O tampão Sörensen foi selecionado neste estudo. A resposta analítica utilizada foi absorvância integrada. Após a otimização foram obtidos os parâmetros analíticos de mérito: faixa linear de trabalho estudada de 5-100 µg L-1; R = 0.9999; RSD = 1,5% (35 µg L-1, n = 7); limite de detecção de 0,8 µg L-1; limite de quantificação de 2,7 µg L-1 e fator de enriquecimento de 92,25. Foram analisadas amostras de água do rio Araranguá e a da rede de abastecimento da cidade de Florianópolis, ambas do estado de Santa Catarina. As duas amostras não apresentaram concentração de níquel acima do limite de detecção e após fortificação das mesmas os valores de recuperação foram na faixa de 100,2 a 103,8%.

Thermodynamic quantities of solvation and dilution for some acetanilide derivatives in octanol and water mutually saturateds

Based on published thermodynamic quantities for solution, partitioning and sublimation of acetanilide (ACN), acetaminophen (ACP) and Phenacetin (PNC), the thermodynamic quantities for drugs solvation in octanol-saturated water (W(ROH)) and water-saturated octanol (ROH(W)) as well as the drugs dilution in ROH(W) were calculated. The Gibbs energies of solvation were favourable in all cases. The respective enthalpies and entropies were negative indicating an enthalpy-driving for the solvation process in all cases. On the other hand, the Gibbs energies of dilution were favourable for ACP and PNC but unfavourable for ACN, whereas the respective enthalpies and entropies were negative for ACP and PNC but positive for ACN indicating enthalpy-driving for the dilution process in the case of the former drugs and entropy-driving for the latter. From the obtained values for the transfer processes, an interpretation based on solute-solvent interactions was developed.

Spectrophotometric determination of metronidazole through Schiff's base system using vanillin and PDAB reagents in pharmaceutical preparations

Two simple sensitive and reproducible spectrophotometric methods have been developed for the determination of metronidazole either in pure form or in their tablets. The proposed methods are based on the reduction of the nitro group to amino group of the drug. The reduction of metronidazole was carried out with zinc powder and 5 N hydrochloric acid at room temperature in methanol. The resulting amine was then subjected to a condensation reaction with aromatic aldehyde namely, vanillin and p-dimethyl amino benzaldehyde (PDAB) to yield yellow colored Schiff's bases. The formed Schiff's bases are quantified spectrophotometrically at their absorption maxima at 422 nm for vanillin and 494 nm for PDAB. Beer's law was obeyed in the concentration ranges 10 to 65 µg mL-1 and 5 to 40 µg mL-1 with a limit of detection (LOD) of 0.080 µg mL-1 and 0.090 µg mL-1 for vanillin and PDAB, respectively. The mean percentage recoveries were found to be 100.05 ± 0.37 and 99.01 ± 0.76 for the two methods respectively. The proposed methods were successfully applied to determine the metronidazole in their tablet formulations and the results compared favorably to that of reference methods. The proposed methods are recommended for quality control and routine analysis.

Inhibitors of Clostridium histolyticum colagenase

Different substances were tested as inhibitors of Clostridium histolyticum collagenase, both experimental and theoretically. The in vitro collagenase activity, alone and in the presence of inhibitors, was quantified by reaction with bovine collagen and dosage of the releasing amino acids. Collagenase-inhibitor interaction was studied theoretically by docking computational calculations. Only one among the tested substances showed inhibitor activity against the bacterial collagenase.

Determination of phenolic compounds and evaluation of antioxidant capacity of Campomanesia adamantium leaves

Five flavanones and three chalcones were isolated from Campomanesia adamantium Berg. (Myrtaceae) leaves. The contents of these compounds were determined by HPLC. The phenolic contents were also determined. The monitoring of the antioxidant activity was carried out by inhibition of peroxidation using the linoleic acid system and radical-scavenging (DPPH). The plants were collected from 4 distinct cities of the Mato Grosso do Sul State, Brazil. The different samples exhibited a range of 4.67-232.35 mg/g chalcones and 15.62-50.71 mg/g flavanones and phenolic contents of the 7.24-21.19 mg/g gallic acid. All extracts showed high antioxidant activity with a wide range of the radical-scavenging (DPPH) from 52.0 to 92.2 % and inhibition oxidation of linoleic acid from 14.6 to 94.2%.

Synthesis and characterization of solid 2-methoxycinnamylidenepyruvic acid

The 2-methoxycinnamylidenepyruvic acid (2-MeO-HCP) was synthesized and characterized for nuclear magnetic resonance (¹H and 13C NMR), mass spectrometry (MS), Infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The application of DSC for purity determination is well documented in literature and is used in the analysis of pure organic compounds. The molecular geometry and vibrational frequencies of 2-MeO-HCP have been calculated.

Desenvolvimento e aplicação de método GC-MS/MS para análise simultânea de 17 HPAs em material particulado atmosférico

Os hidrocarbonetos policíclicos aromáticos (HPAs) estão associados ao aumento da incidência de diversos tipos de cânceres no homem. Essas moléculas são formadas principalmente na queima incompleta de matéria orgânica, sendo encontradas em todos os compartimentos ambientais. Órgãos regulamentadores das áreas ambiental e de saúde ocupacional consideram 17 HPAs como contaminantes atmosféricos prioritários. Este trabalho apresenta um método para análise simultânea destes HPAs utilizando-se a cromatografia a gás acoplada à espectrometria de massas operando no modo tandem (GC-MS/MS). Os limites de detecção e quantificação do método mostraram-se até 5 vezes inferiores aos obtidos no método GC-MS (SCAN). O método mostrou-se seletivo para análise de HPAs em extratos de amostras de material particulado atmosférico. Uma análise comparativa de dois sistemas de solventes (diclorometano/metanol 4:1 v/v e hexano/acetona 1:1 v/v) para a extração de HPAs, utilizando amostras de material particulado atmosférico, revelou que ambas as misturas de solventes possuem poder de extração semelhante. Os resultados sugerem que é possível realizar extração de HPAs de material particulado atmosférico em ultra-som com a mistura hexano/acetona (1:1), que é menos tóxica em relação à mistura diclorometano/metanol (4:1), bastante utilizada nestas análises, sem perdas significativas na exatidão do método.