New series of metal complexes by amphiphilic biopolymeric Schiff bases from modified chitosans: Preparation, characterization and effect of molecular weight on its biological applications.

To improve biological activity of chitosans, new Zn(II), Pd(II) and Pt(II) complexes with biopolymeric amphiphilic Schiff bases anchored in different molecular weight chitosans matrices modified with salicylaldehyde and glycidol were prepared. Salicylaldehyde was introduced to generate complexing Schiff base sites in the chitosans matrix while glycidol is intended to increase the water solubility of the resulting biopolymeric complexes. These novel complexes were characterized using various techniques and assayed for antimicrobial and antitumor activity. The effectiveness of modification was evaluated using FTIR spectroscopy, and thermal behavior of the complexes by TG/DTG-DTA. XPRD showed that the crystallinity of the ligand diminished after the metal complexation. Surface morphologies, investigated by SEM, revealed that the complexes are rougher than chitosan matrix, and the presence of metallic ions was confirmed by EDX. Electronic spectra suggested square planar geometry for Pd(II) and Pt(II) complexes. Concerning antimicrobial activity, the novel complexes exhibited higher antibacterial efficiency against Pseudomonas syringae than against the Fusarium graminearum fungi regarding the free ligand. Complexes also exhibited high antitumor effects against the MCF-7 breast cancer cells, with certain selectivity regarding non-tumor cells (Balb/C 3T3 clone A31) depending on concentration and molar mass, indicating that they could potentially be used for antitumor applications.

Simultaneous determination of environmental contaminants using a graphite oxide - Polyurethane composite electrode modified with cyclodextrin.

A composite electrode based on graphite oxide (GrO)-polyurethane (PU) modified with ß-cyclodextrin (CD) was proposed for the simultaneous determination of three drugs: terbutaline (TER), nimesulide (NIM), and methocarbamol (MET), as possible contaminants in river water samples. To evaluate the performance of the proposed CD-GrOPUE, voltammetric techniques were used and two other electrodes were fabricated (GrOPUE and GrPUE) for comparison. The functionalization of the GrO was confirmed by scanning electron microscopy images, energy-dispersive X-ray spectroscopy analysis, and thermogravimetry. Cyclic voltammograms obtained for TER, NIM, and MET indicated an irreversible behaviour at 0.6 V, 0.9 V and 1.2 V (vs. Ag/AgCl (3 mol L-1 KCl)), respectively, on each working electrode, with the highest peak current values been obtained using the CD-GrOPUE. Under optimal conditions, using square-wave voltammetry, the linear ranges obtained (and limit of detection) for TER, NIM, and MET were 2.5-30 (0.55), 0.62-7.3 (0.083), and 0.62-7.3 (0.077) µmol L-1, respectively. The analytical method developed were applied in the simultaneous determination of TER, NIM, and MET in river water samples, with results like those obtained using a reference spectrophotometric method (at a confidence level of 95%). One can conclude, that the modification of GrO with CD arrays made possible the development of a robust and simple sensor platform for environmental analyses.

The influence of reaction parameters on complexation of Zn(II) complexes with biopolymeric Schiff bases prepared from chitosan and salicylaldehyde.

Influence of some reactional parameters as mol ratio (Schiff base:metal), solvent, temperature and reaction time were evaluated in order to improve the extension of complexation during the preparation of zinc complexes of biopolymeric Schiff base from chitosan and salicylaldehyde. Zinc(II) complex was used as a model system in order to improve the degree of complexation for further synthesis of different Schiff bases complexes from other aldehydes and metallic centers. The complexation yields for each synthesis were estimated on the basis of the zinc oxide formed after thermal degradation. Thus thermogravimetry was used to determine the experimental percentage of metal that interact with the free biopolymeric Schiff base. In conclusion, complexation reaction of zinc(II) with biopolymeric Schiff bases was more effective at 40 °C in ethanol as a solvent with intermediary dielectric constant, which resulted in higher metallic contents. Other experimental conditions that resulted in highest degree of complexation were mol ratio 1.0:1.0 (mol/mol, Schiff base:metal), reaction temperature 40 °C and reaction time of 8 h in ethanol. Biological activity of free ligand and its Zn(II) complex obtained under optimized conditions were evaluated against tumor cells.

Comparative performances of a bare graphite-polyurethane composite electrode unmodified and modified with graphene and carbon nanotubes in the electrochemical determination of escitalopram.

A bare composite graphite-polyurethane electrode (EGPU) and two other modified with graphene (EGPU-GR) and functionalized multi-walled carbon nanotubes (EGPU-CNTs) were prepared and compared regarding their voltammetric response to escitalopran (EST). The modifiers were characterized by Raman spectroscopy and the resulting electrode materials by contact angle measurements with a hydrophilicity character in the ascending order for the composites: GPU > GPU-GR > GPU-CNTs and scanning electron microscopy (SEM). The electroactive areas of the EGPU, EGPU-GR, and EGPU-CNTs were 0.065, 0.080, and 0.092cm2, respectively, calculated from the chronocoulometry using K3[Fe(CN)6] as a probe and the Cottrell equation. The cyclic voltammograms obtained for EST indicated irreversible electrochemical behavior, with an anodic peak at ca. +0.80V (νs. SCE). These measurements were carried out with the three electrodes, and comparison of the analytical responses led to the EGPU-GR electrode being selected for use in the subsequent experiments. Under optimal conditions, square wave and differential pulse voltammetry at EGPU-GR presented linear dynamic ranges between 1.5 × 10-6 and 1.2 × 10-5mol L-1, with a detection limit of 2.5 × 10-7molL-1 (SWV) and 1.5 × 10-6 and 1.2 × 10-5molL-1, with a detection limit of 3.2 × 10-7molL-1 (DPV) for EST. The proposed method was applied for the quantification of EST in synthetic urine and cerebrospinal fluid samples, offering advantages including simplicity of fabrication, no requirement for analyte preconcentration and surface renewal, fast response, and selectivity.

Synthesis, Characterization and Biological Activities of Biopolymeric Schiff Bases Prepared with Chitosan and Salicylaldehydes and Their Pd(II) and Pt(II) Complexes.

In an attempt to enhance chitosan biological activities, biopolymeric Schiff bases of chitosan and different salicylaldehydes and their palladium(II) and platinum(II) complexes were synthesized and tested. The chemical structures of these derivatives were characterized using ¹H-NMR, FTIR spectroscopy and XPRD. Thermal analysis was done through TGA/DTG-DTA. Electronic absorption spectra and surface morphologies were analyzed by SEM-EDAX. Chitosan and its derivatives were evaluated for their in vitro antimicrobial activity against two common bacterial and fungal plant pathogens Pseudomonas syringae pv. tomato and Fusarium graminearum, respectively, and for their antitumor activity against a human breast cancer cell line (MCF-7). It was found that, compared to the nonmodified chitosan, chitosan modified with Schiff bases and their complexes was highly toxic against the MCF-7 cell line and had antibacterial effects against P. syringea. However, the modified chitosan derivatives had less pronounced antifungal effects against F. graminearum compared to the nonmodified chitosan, suggesting different modes of action.

Synthesis, characterization and biological activity of Cu(II), Ni(II) and Zn(II) complexes of biopolymeric Schiff bases of salicylaldehydes and chitosan.

Schiff bases have been prepared from biopolymer chitosan and salicylaldehyde, 5-methoxysalicylaldehyde, and 5-nitrosalicylaldehyde. Ligands were synthesized in a 1:1.5mol ratio, and their Cu(II), Ni(II) and Zn(II) complexes in a 1:1mol ratio (ligand:metal). Ligands were characterized by 1H NMR and FTIR, resulting in degrees of substitution from 43.7 to 78.7%. Complexes were characterized using FTIR, electronic spectra, XPRD. The compounds were confirmed by the presence of an imine bond stretching in the 1630-1640cm-1 and νMetal-N and νMetal-O at <600cm-1. Electronic spectra revealed that both Cu(II) and Ni(II) complexes present a square plane geometry. The crystallinity values were investigated by X-ray powder diffraction. Thermal behavior of all compounds was evaluated by TGA/DTG and DTA curves with mass losses related to dehydration and decomposition, with characteristic events for ligand and complexes. Schiff base complexes presented lower thermal stability and crystallinity than the starting chitosan. Residues were the metallic oxides as confirmed by XPRD, whose amounts were used in the calculation of the percentage of complexed metal ions. Surface morphologies were analyzed with SEM-EDAX. Preliminary cytotoxicity tests were performed using MTT assay with HeLa cells. Despite the differences in solubility, the free bases presented relatively low toxicity.

Thermoanalytical studies of carbamazepine: hydration/dehydration, thermal decomposition, and solid phase transitions

Carbamazepine (CBZ), a widely used anticonvulsant drug, can crystallize and exhibits four polymorphic forms and one dihydrate. Anhydrous CBZ can spontaneously absorb water and convert to the hydrate form whose different crystallinity leads to lower biological activity. The present study was concerned to the possibility of recovering the hydrated form by heating. The thermal behavior of spontaneously hydrated carbamazepine was investigated by TG/DTG-DTA and DSC in dynamic atmospheres of air and nitrogen, which revealed that the spontaneous hydration of this pharmaceutical resulted in a Form III hydrate with 1.5 water molecules. After dehydration, this anhydrous Form III converted to Form I, which melted and decomposed in a single event, releasing isocyanic acid, as shown by evolved gas analysis using TG-FTIR. Differential scanning calorimetry analyses revealed that Form III melted and crystallized as Form I, and that subsequent cooling cycles only generated Form I by crystallization. Solid state decomposition kinetic studies showed that there was no change in the substance after the elimination of water by heating to 120 °C. Activation energies of 98 ± 2 and 93 ± 2 kJ mol-1 were found for the hydrated and dried samples, respectively, and similar profiles of activation energy as a function of conversion factor were observed for these samples.

A carbamazepina (CBZ) é um anticonvulsivante frequentemente utilizado no Brasil e em vários países. Ela apresenta quatro formas polimórficas e um diidrato. Todas as formas são ativas farmacologicamente, porém a Forma III é a preferível do ponto de vista farmacêutico, em função de suas propriedades físico-químicas. Entretanto, essa forma é altamente higroscópica, podendo converter-se ao diidrato, menos ativo biologicamente. Nesse trabalho propõe-se avaliar o comportamento térmico da forma hidratada, visando à recuperação da forma ativa, por aquecimento. Para tanto, foi feito um estudo do comportamento térmico por TG/DTG-DTA e DSC em atmosfera dinâmica de ar e nitrogênio, que evidenciou hidratação espontânea da Forma III, gerando um hidrato contendo 1,5 moléculas de água. Essa forma sofre desidratação, seguida de fusão e conversão para a Forma I. Segue-se a decomposição em uma única etapa, na qual ocorre liberação do ácido isociânico, conforme análise de gases evolvidos, por termogravimetria acoplada ao infravermelho (TG-FTIR). Estudos por calorimetria exploratória diferencial mostraram que a Forma III se funde e se cristaliza imediatamente na Forma I, durante o aquecimento. A Forma I também se funde e ciclos de aquecimento/resfriamento posteriores evidenciaram que a substância se cristaliza apenas na Forma I por resfriamento. Estudos cinéticos da decomposição, em estado sólido, mostraram que não há alteração na substância pela eliminação da água por aquecimento, sendo determinados valores de energia de ativação da ordem de 98 ± 2 e 93 ± 2 kJ mol-1, respectivamente, para a amostra hidratada e submetida à secagem, assim como perfis semelhantes nas curvas de energia de ativação em função do fator de conversão.

Flow-injection spectrophotometric determination of captopril in pharmaceutical formulations using a new solid-phase reactor containing AgSCN immobilized in a polyurethane resin

A simple flow-injection analysis procedure was developed for determining captopril in pharmaceutical formulations employing a novel solid-phase reactor containing silver thiocyanate immobilized in a castor oil derivative polyurethane resin. The method was based on silver mercaptide formation between the captopril and Ag(I) in the solid-phase reactor. During such a reaction, the SCN- anion was released and reacted with Fe3+, which generated the FeSCN2+ complex that was continuously monitored at 480 nm. The analytical curve was linear in the captopril concentration range from 3.0 × 10-4 mol L-1 to 1.1 × 10-3 mol L-1 with a detection limit of 8.0 × 10-5 mol L-1. Recoveries between 97.5% and 103% and a relative standard deviation of 2% for a solution containing 6.0 × 10-4 mol L-1 captopril (n = 12) were obtained. The sample throughput was 40 h-1 and the results obtained for captopril in pharmaceutical formulations using this procedure and those obtained using a pharmacopoeia procedure were in agreement at a 95% confidence level.

Um procedimento simples de análise por injeção em fluxo foi desenvolvido para a determinação de captopril em formulações farmacêuticas empregando um novo reator em fase sólida contendo tiocianato de prata imobilizado em resina poliuretana obtida a partir de óleo de mamona. O método foi baseado na formação de um mercapto composto de prata, no reator em fase sólida, obtido entre o captopril e Ag (I) imobilizada. Durante a reação, íons SCN- eram liberados e reagiam com Fe3+, gerando o complexo FeSCN2+, que foi continuamente monitorado em 480 nm. A curva analítica foi linear no intervalo de concentração de captopril entre 3,0 × 10-4 a 1,1 × 10-3 mol L-1 com um limite de detecção de 8,0 × 10-5 mol L-1. Recuperações entre 97,5-103% e desvio padrão relativo de 2% para uma solução contendo 6,0 × 10-4 mol L-1 de captopril (n = 12) foram obtidos. A frequência de amostragem foi de 40 h-1 e os resultados obtidos para captopril em formulações farmacêuticas utilizando este procedimento e o da Farmacopeia, estão de acordo em um nível de confiança de 95%.

Graphite-silicone rubber composite electrode: Preparation and possibilities of analytical application.

Composite electrodes were prepared using graphite powder and silicone rubber in different compositions. The use of such hydrophopic materials interned to diminish the swallowing observed in other cases when the electrodes are used in aqueous solutions for a long time. The composite was characterized for the response reproducibility, ohmic resistance, thermal behavior and active area. The voltammetric response in relation to analytes with known voltammetric behavior was also evaluated, always in comparison with the glassy carbon. The 70% (graphite, w/w) composite electrode was used in the quantitative determination of hydroquinone (HQ) in a DPV procedure in which a detection limit of 5.1x10(-8)molL(-1) was observed. HQ was determined in a photographic developer sample with errors lower then 1% in relation to the label value.

Evaluation of a carbon paste electrode modified with organofunctionalised SBA-15 nanostructured silica in the simultaneous determination of divalent lead, copper and mercury ions.

The performance of a carbon paste electrode (CPE) modified with SBA-15 nanostructured silica organofunctionalised with 2-benzothiazolethiol in the simultaneous determination of Pb(II), Cu(II) and Hg(II) ions in natural water and sugar cane spirit (cachaça) is described. Pb(II), Cu(II) and Hg(II) were pre-concentrated on the surface of the modified electrode by complexing with 2-benzothiazolethiol and reduced at a negative potential (-0.80 V). Then the reduced products were oxidised by DPASV procedure. The fact that three stripping peaks appeared on the voltammograms at the potentials of -0.48 V (Pb2+), -0.03 V (Cu2+) and +0.36 V (Hg2+) in relation to the SCE, demonstrates the possibility of simultaneous determination of Pb2+, Cu2+ and Hg2+. The best results were obtained under the following optimised conditions: 100 mV pulse amplitude, 3 min accumulation time, 25 mV s(-1) scan rate in phosphate solution pH 3.0. Using such parameters, calibration graphs were linear in the concentration ranges of 3.00-70.0 x 10(-7) mol L(-1) (Pb2+), 8.00-100.0 x 10(-7) mol L(-1) (Cu2+) and 2.00-10.0 x 10(-6) mol L(-1) (Hg2+). Detection limits of 4.0 x 10(-8) mol L(-1) (Pb2+), 2.0 x 10(-7) mol L(-1) (Cu2+) and 4.0 x 10(-7) mol L(-1) (Hg2+) were obtained at the signal noise ratio (SNR) of 3. The results indicate that this electrode is sensitive and effective for simultaneous determination of Pb2+, Cu2+ and Hg2+ in the analysed samples.

Determination of atenolol at a graphite-polyurethane composite electrode.

A bare graphite-polyurethane composite was evaluated as an alternative electrode in the determination of atenolol (ATN) in pharmaceutical formulations. Using a DPV procedure, a linear analytical curve was observed in the 4-100mumolL(-1) range with a LOD=3.16mumolL(-1), without need of surface renewing between successive runs, with recoveries between 95.5 and 108%. Interference of other antihypertensive drugs was observed, but not from the usual components of tablets. The results of the proposed method agreed with HPLC ones within 95% confidence level.

The use of a graphite-castor oil polyurethane composite electrode for the determination of hydroquinone in photographic developers.

The performance of a new graphite-castor oil polyurethane composite electrode in the determination of hydroquinone in photographic developers in a differential pulse voltammetric (DPV) procedure is described. The 60% (graphite, w/w) composite electrode presented good stability, repeatability and accurate response. Limit of detection of 934 nmol L(-1) was observed for hydroquinone within a linear dynamic range from 66 to 530 nmol L(-1). The determination of hydroquinone in a photographic developer sample showed agreement with the label values in a 95% confidence level with maximum 2% relative error and recoveries between 100.1 and 100.4%. No need of sample preparation was required since the p-methylaminophenolsulfate (metol) present in the developer formulation did not interfered in the measurements.

Evaluation of the electrochemical behavior and analytical potentialities of a carbon paste electrode modified with a ruthenium (III) piperidinedithiocarbamate complex.

The preparation and electrochemical characterization of a carbon paste electrode modified with bis(N,N-piperidinedithiocarbamate)-mu-tris(N,N-piperidinedithiocarbamate)diruthenium(III) complex, alpha-[Ru2(Pip)5]Cl are described. The best voltammetric response was obtained for a 10% (m/m) alpha-[Ru2(Pip)5]Cl content in the paste, potassium acid phthalate solution pH 4.0 as supporting electrolyte and scan rate of 100 mV s-1. The analytical potentialities of the electrode have been evaluated using L-ascorbic acid (vitamin C) as a probe. A sensitive linear voltammetric response for L-ascorbic acid was obtained in the concentration range 4.50-113x10(-5) mol l-1 (7.92-200 mg l-1) with a slope of 1.12x10(4) microA mol-1, and a detection limit (3sigma/slope) of 7.00x10(-6) mol l-1 using cyclic voltammetry. The concentrations of L-ascorbic acid in pharmaceutical formulations (tablets and liquid) were determined using the modified electrode and compared with an iodimetric procedure with good agreement at the 95% confidence and relative error lower than 1%.

The use of carbon paste electrode in the direct voltammetric determination of tryptophan in pharmaceutical formulations.

A simple, fast and sensitive method is proposed for Tryptophan (Trp) determination in pharmaceutical formulations containing other non-electroative aminoacids, vitamins and hydroxycobalamines. Optimized conditions for differential pulse voltammetry allowed the determination of Trp with detection limit of 1.7 microM in 2-30 mM linear dynamic range (n=7; r=0.999), at a bare, non-treated carbon paste electrode. Ascorbic acid interference was evaluated and eliminated by choosing a suitable baseline for determination of peak currents for Trp.