O estudo das Relações Quantitativas entre Estrutura química e Atividade biológica (QSAR/QSAR-3D) utilizando diferentes estratégias metodológicas complementares, aplicadas iterativamente, se estende a diferentes áreas de aplicação. Dentre elas destaca-se o planejamento racional de novos fármacos e o estudo de seus mecanismos de ação. Moléculas candidatas a fármacos, geradas em estudos de QSAR-3D, freqüentemente, não se tomam fármacos por apresentarem inadequadas propriedades farmacocinéticas, ou seja, ADME (absorção, distribuição, metabolismo e excreção). Nota-se assim que o conhecimento das propriedades farmacocinéticas de ligantes deve ser uma preocupação presente, em qualquer nível de desenvolvimento de um novo fármaco e ressalta-se a importância do QSAR como uma ferramenta de grande valor, principalmente na compreensão da contribuição das propriedades físico-químicas, identificadas como sendo responsáveis pela atividade. A aplicação do QSAR permite elucidar a natureza e a grandeza das propriedades físico-químicas e estruturais nas interações entre o composto e o seu alvo biológico nos processos farmacocinéticos de ADME (TESTA, 2001; MALVEZZI et al.,, 2001; GAVIRAGHI et al., 2001). Recentemente...
Pós-graduação em Química - IQ; This paper focused on fertilization procedures (nitrogen, potassium and phosphorous) in Agriculture. We have undertaken an investigation of new materials for coating surfaces of fertilizer and also studied methodologies of measurement, aiming to evaluate the performance of the products in measures of CRF (Controlled Release of Fertilizer), with direct applications in products and processes. The polymer used to coat urea, KCl and MAP (monoammonium phosphate) was developed based on a styrenated acrylic resin. In the formulation of the polymer application were used as sugar cane molasses and vinasse compounds and on the application process was added CaCO3 or CaSO4, with these decisive role in gradual release process by a cation exchange mechanism that promotes preferential release of ammonium. This paper presents a summary on the topic, reactions, structures and chemical properties related to the dissolution controlled urea and other nutrients survey. The polymer used to control the process of the slow release of the species soluble in water (moisture) of the soil was assessed from measurement techniques based on accelerated dissolution in aqueous systems, developed employing Condutometry and Potentiometry (Ion Selective Electrode). Also was investigated comparatively the salt effect of KCl and KCl coated on the ground. The polymer was chemically designed to display favorable structural and chemical properties focusing on nutrient economy (reduction of applied doses). The modified polymer applied in the lining of the nutrient was characterized by thermal analysis of DSC (Defferential Scanning Calorimetry) and TG (Thermogravimetry)...
A highly selective PVC membrane electrode based on a cobalt-salophen complex was prepared. The sensor displays an anti-Hofmeister selectivity sequence with a preference for iodide ion over many common anions. The electrode has a linear dynamic range between 5.0×10-7 to 1.0×10-1 mol L-1, with a Nernstian slope of -58.9 mV decade-1 and a detection limit of 3.0×10-7 mol L-1. The working pH range of the sensor is 3.1-9.8. It exhibits of a fast as 15 s and has a lifetime of about 2 months. The selectivity coefficients for the proposed electrode were improved for some interferences, when compared with those of available iodide membrane electrode. The proposed electrode was successfully applied for the direct determination of iodide in edible salt and as an indicator electrode in potentiometric titration of I- against Ag+.
The 5,6-benzo-4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8,8,8]hexacos-5-ene (BHDE) was used as an excellent ionophore in construction of a Zn(II) PVC-based membrane sensor. The best performance was obtained with a membrane composition of 30% poly(vinyl chloride), 64.5% nitrobenzen (NB), 2.5% BHDE and 3% sodium tetraphenylborate (NaTPB). This sensor shows very good selectivity and sensitivity towards zinc ion over a wide variety of cations, including alkali, alkaline earth, transition and heavy metal ions. The sensor revealed a great enhancement in selectivity coefficients for zinc ions, in comparison to the previously reported zinc sensors. The proposed sensor exhibits a Nernstian behavior (with slope of 29.1 ± 0.4 mV per decade) over a wide concentration range (1.0 ´ 10-6-1.0 ´ 10-1 mol L-1) with a detection limit of 6.3 ×10-7 mol L-1 (41.2 ng mL-1). It shows relatively fast response time, in the whole concentration range (< 10s), and can be used for at least 10 weeks in a pH range of 2.8-7.3. The proposed sensor was successfully used in direct determination of zinc ions in wastewater of industrial zinc electroplating companies, and also as an indicator electrode in titration with EDTA.
The characteristics, performance, and application of an electrode, namely, Pt|Hg|Hg2(NAP)2|Graphite, where NAP stands for naproxenate ion, are described. This electrode responds to NAP with sensivity of (58.1± 0.9) mV decade-1 over the range 5.0 x 10-5 - 1.0 x 10-2 mol L-1 at pH 6.0-9.0 and a detection limit of 3.9 x 10-5 mol L-1. The electrode is easily constructed at a relatively low cost with fast response time (within 10-35 s) and can be used for a period of 6 months without any considerable divergence in potentials. The proposed sensor displayed good selectivity for naproxen in the presence of several substances, especially concerning carboxylate and inorganic anions. It was used for the direct assay of naproxen in commercial tablets by means of the standard additions method. The analytical results obtained by using this electrode are in good agreement with those given by the United States Pharmacopeia procedure.
A highly selective and sensitive monohydrogen phosphate (MHP) sensor has been fabricated by constructing a poly vinyl chloride (PVC) matrix membrane containing a new oxo-molybdenum methyl-salen (MS) as a neutral carrier, hexadecyltrimethyl ammonium bromide (HTAB) as a cationic additive, benzylacetate (BA) as a plasticizing solvent mediator. The membrane sensor exhibits linear potential response in the concentration range of 1.0 ×10-1 - 4.0 × 10-7 mol L-1 of MHP. The electrode displays a Nernstian slope of -28.6 ± 0.3 mV decade-1 in the pH of 8.5. The proposed sensor also exhibits a fast response time of
This article describes the fabrication of a novel and selective polyvinylchloride (PVC) membrane potentiometric sensor for Al3+ cation based on 12-crown-4 (12C4) as an ionophore. The electrode was prepared by coating the surface of a graphite rod by a membrane containing PVC as a plastic matrix, dibutylphthalate (DBP) as plasticizer, 12C4 as an ionophore and oleic acid (OA) as an additive. Under optimized membrane composition, the constructed electrochemical sensor exhibited a Nernstian response for Al3+ cation concentration, ranging from 1.0 × 10-6 to 1.0 × 10-1 mol L-1 with a detection limit of 5.5 × 10-7 mol L-1 and a slope of 19.0 ± 0.4 mV per decade at 25 °C. The constructed potentiometric sensor showed a relatively fast response time (15 s), good reproducibility and stability, and high selectivity towards Al3+ cation in solutions. The proposed sensor was successfully used as an indicator electrode in potentiometric titration and also in the direct determination of this metal cation in real samples.
Equilibrium dialysis of dog serum albumin (DSA) against Ni(II) in 0.1 M-N-ethylmorpholine/HCl, pH 7.53, demonstrates the absence of a specific Ni(II)-binding site in DSA. To evaluate at the molecular level the influence of the genetic substitution of L-tyrosine for L-histidine at the N-terminal of DSA, a simple model tripeptide of the N-terminal residues, glycylglycyl-L-tyrosine N-methylamide, was synthesized and its Ni(II)-binding properties studied. A comparison of the visible absorption characteristics of Ni(II)-DSA with those of Ni(II)-glycylglycyl-L-tyrosine N-methylamide reveals a similar change from octahedral to planar co-ordination as the pH is increased. Both systems exhibit a low Ni(II)-binding affinity at physiological pH, with DSA binding a greater percentage of Ni(II) owing to the availability of at least two binding sites of similar affinities. The complex equilibria between Ni(II) and glycylglycyl-L-tyrosine N-methylamide were studied by analytical potentiometry (0.15 M-NaCl, 25 degrees C). Four major complex species, MHA, MH-1A2, MH-2A2 and MH-3A [where M and A represent Ni(II) ion and anionic peptide respectively], were detected, MHA being the single species at physiological pH. There is no evidence for the involvement of the phenolic hydroxy group in the octahedral MHA complex...
Polymer membrane ion-selective electrodes containing lipophilic ionophores are traditionally interrogated by zero current potentiometry, which, ideally, gives information on the sample activity of ionic species. It is shown here that a discrete cathodic current pulse across an H+-selective polymeric membrane doped with the ionophore ETH 5294 may be used for the chronopotentiometric detection of pH in well buffered samples. However, a reduction in the buffer capacity leads to large deviations from the expected Nernstian response slope. This is explained by the local depletion of hydrogen ions at the sample-membrane interface as a result of the galvanostatically imposed ion flux in direction of the membrane. This depletion is found to be a function of the total acidity of the sample and can be directly monitored chronopotentiometrically in a flash titration experiment. The subsequent application of a baseline potential pulse reverses the extraction process of the current pulse, allowing one to interrogate the sample with minimal perturbation. In one protocol, total acidity is found to be proportional to the magnitude of applied current at the flash titration endpoint. More conveniently, the square root of the flash titration endpoint time observed at a fixed applied current is a linear function of the total acid concentration. This suggests that it is possible to perform rapid localized pH titrations at ion-selective electrodes without the need for volumetric titrimetry. The technique is explored here for acetic acid...
This paper gives an overview of the newest developments of polymeric membrane ion-selective electrodes. A short essence of the underlying theory is given, emphasizing how the electromotive force may be used to assess binding constants of the ionophore, and how the selectivity and detection limit are related to the underlying membrane processes. The recent developments in lowering the detection limits of ISEs are described, including recent approaches of developing all solid state ISEs, and breakthroughs in detecting ultra-small quantities of ions at low concentrations. These developments have paved the way to use potentiometric sensors as in ultra-sensitive affinity bioanalysis in conjunction with nanoparticle labels. Recent results establish that potentiometry compares favorably to electrochemical stripping analysis. Other new developments with ion-selective electrodes are also described, including the concept of backside calibration potentiometry, controlled current coulometry, pulsed chronopotentiometry, and localized flash titration with ion-selective membranes to design sensors for the direct detection of total acidity without net sample perturbation. These developments have further opened the field for exciting new possibilities and applications.
The coordination chemistry of bisphosphonates with Yb3+ was investigated to evaluate the potential of the UV-Vis based detection method using the Yb3+-pyrocatechol complexation reaction as a sensor for bisphosphonates. The complexation chemistry of Yb3+ with phosphate and ATP analogs was previously described (E. Gaidamauskas et al J. Biol. Inorg. Chem. 13 (2008) 1291-1299), and we here study the complexation chemistry of bisphosphonates in this system. The spectrophotometric assay yields direct evidence for formation of a 4:3 metal to ligand complex at neutral pH. Direct evidence for Yb3+ : methylenebis(phosphonate) complexes with 1:1 and 1:2 stoichiometry was also obtained by potentiometry at acidic and basic pH. Direct evidence for complex formation was obtained using 1H NMR spectroscopy although the stoichiometry was not accessed at neutral pH. Our results suggest that the spectroscopic observation of the YbPV complex can be used to conveniently measure concentrations of bisphosphonates down to 2-3 μM .
The fabrication and electrochemical evaluation of two PVC membrane-based Ion-Selective electrodes responsive for ramipril drug have been proposed. The sensitive membranes were prepared using ramipril-phosphomolibdate and ramipril-tetraphenylborate ion-pair complexes as electroactive sensing materials in plasticized PVC support. The electrodes based on these materials provide near-Nernestian response (sensitivity of 53 ± 0.5–54 ± 0.5 mV/concentration decade) covering the concentration range of 1.0 × 10−2–1.0 × 10−5 mol L−1 with a detection limit of 3.0 × 10−6–4.0 × 10−6 mol L−1. The suggested electrodes have been successfully used in the determination of ramipril drug in some pharmaceutical formulations using direct potentiometry with average recovery of >96% and mean standard deviation of <3% (n = 5).
Two manganese(III) porphyrins: manganese(III) tetraphenylporphyrin chloride and manganese(III)-tetrakis(3-hydroxyphenyl)porphyrin chloride were tested as ionophores for the construction of new diclofenac–selective electrodes. The electroactive material was incorporated either in PVC or a sol–gel matrix. The effect of different plasticizers and additives (anionic and cationic) on the potentiometric response was studied. The best results were obtained for the PVC membrane plasticized with dioctylphtalate and having sodium tetraphenylborate as a lipophilic anionic additive incorporated. The sensor response was linear in the concentration range 3 × 10−6 – 1 × 10−2 M with a slope of −59.7 mV/dec diclofenac, a detection limit of 1.5 × 10−6 M and very good selectivity coefficients. It was used for the determination of diclofenac in pharmaceutical preparations, by direct potentiometry. The results were compared with those obtained by the HPLC reference method and a good agreement was found between the two methods.
Platinum(IV) am(m)ine complexes are of interest as potential anticancer pro-drugs, but there are few reports of their acid–base properties. We have studied the acid–base properties of three photoactivatable anticancer platinum(IV)-diazidodiam(m)ine complexes (cis,trans,cis-[PtIV(N3)2(OH)2(NH3)2], trans,trans,trans-[PtIV(N3)2(OH)2(NH3)2], and cis,trans-[PtIV(N3)2(OH)2(en)]) using multinuclear NMR methods and potentiometry. In particular, the combination of both direct and indirect techniques for the detection of 15N signals has allowed changes of the chemical shifts to be followed over the pH range 1–11; complementary 14N NMR studies have been also carried out. A distinct pKa value of approximately 3.4 was determined for all the investigated complexes, involving protonation/deprotonation reactions of one of the axial hydroxido groups, whereas a second pH-dependent change for the three complexes at approximately pH 7.5 appears not to be associated with a loss of an am(m)ine or hydroxido proton from the complex. Our findings are discussed in comparison with the limited data available in the literature on related complexes.
Differential scanning calorimetry, laser Raman spectroscopy, optical densitometry, and pH potentiometry have been used to investigate DNA melting profiles in the presence of the chloride salts of Ba2+, Sr2+, Mg2+, Ca2+, Mn2+, Co2+, Ni2+, and Cd2+. Metal-DNA interactions have been observed for the molar ratio [M2+]/[PO2-] = 0.6 in aqueous solutions containing 5% by weight of 160 bp mononucleosomal calf thymus DNA. All of the alkaline earth metals, plus Mn2+, elevate the melting temperature of DNA (Tm > 75.5 degrees C), whereas the transition metals Co2+, Ni2+, and Cd2+ lower Tm. Calorimetric (delta Hcal) and van't Hoff (delta HVH) enthalpies of melting range from 6.2-8.7 kcal/mol bp and 75.6-188.6 kcal/mol cooperative unit, respectively, and entropies from 17.5 to 24.7 cal/K mol bp. The average number of base pairs in a cooperative melting unit () varied from 11.3 to 28.1. No dichotomy was observed between alkaline earth and transition DNA-metal complexes for any of the thermodynamic parameters other than their effects on Tm. These results complement Raman difference spectra, which reveal decreases in backbone order, base unstacking, distortion of glycosyl torsion angles, and rupture of hydrogen bonds, which occur after thermal denaturation. Raman difference spectroscopy shows that transition metals interact with the N7 atom of guanine in duplex DNA. A broader range of interaction sites with single-stranded DNA includes ionic phosphates...
In the present work, a study of the effect of anions, cations and pH in the potentiometric response of a graphite-epoxy composite is reported. The results obtained indicate a better response for anionic than for cationic ions, with those of greater magnitude being towards OH- and H+ respectively. It is possible to give an explication that is in agreement with the results obtained, for some behaviors in the response of chemical sensors and biosensors based on the study of this transducer; likewise some interesting direct and practical applications, are suggested and explored.
Corrosion of rebar in concrete is commonly associated with, and to a large degree influenced by, the free chloride concentration in the pore water. The amount of chloride in concrete is important because chloride can promote corrosion of steel reinforcement when moisture and oxygen are present. A potentiometric procedure that makes use of direct measurement with a chloride ion selective electrode has been developed to analyze free chloride in the pore water extracted from cement paste.16 The accuracy and reliability of this analytical technique has been checked against a certified reference material, Merck sodium chloride solution. Confidence levels (CL095), of 0.03 and relative standard deviations of 0.2 % for chloride were determined for ordinary Portland cement (OPC) chloride binding capacity.