Probing the mid-gorge of cholinesterases with spacer-modified bivalent quinazolinimines leads to highly potent and selective butyrylcholinesterase inhibitors

The spacer structure of homobivalent quinazolinimes acting as potent acetyl-(AChE)- and butyrylcholinesterase (BChE) inhibitors was chemically modified introducing tertiary amine and acyl-amide moieties, and the activities at both ChEs were evaluated. Molecular docking was applied to explain the data and probe the capacity of the mid-gorge site of both ChEs. The novel spacer structures considerably alter the biological profile of bivalent quinazolinimines with regard to both inhibitory activity and selectivity. Mutual interaction of binding to the various sites of the enzymes was further investigated by applying also different spacer lengths and ring sizes of the alicycle of the tricyclic quinazolinimines. In order to achieve selectivity toward BChE and to improve inhibitory activities, the spacer structure was optimized and identified a highly potent and selective BChE inhibitor. (C) 2010 Elsevier Ltd. All rights reserved.

Modified Silicone Elastomer Vaginal Gels for Sustained Release of Antiretroviral HIV Microbicides

We previously reported nonaqueous silicone elastomer gels (SEGs) for sustained vaginal administration of the CCR5-targeted entry inhibitor maraviroc (MVC). Here, we describe chemically modified SEGs (h-SEGs) in which the hydrophobic cyclomethicone component was partially replaced with relatively hydrophilic silanol-terminated polydimethylsiloxanes (st-PDMS). MVC and emtricitabine (a nucleoside reverse transcriptase inhibitor), both currently under evaluation as topical microbicides to counter sexual transmission of human immunodeficiency virus type 1 (HIV-1), were used as model antiretroviral (ARV) drugs. Gel viscosity and in vitro ARV release were significantly influenced by st-PDMS molecular weight and concentration in the h-SEGs. Unexpectedly, gels prepared with lower molecular weight grades of st-PDMS showed higher viscosities. h-SEGs provided enhanced release over 24 h compared with aqueous hydroxyethylcellulose (HEC) gels, did not modify the pH of simulated vaginal fluid (SVF), and were shown to less cytotoxic than standard HEC vaginal gel. ARV solubility increased as st-PDMS molecular weight decreased (i.e., as percentage hydroxyl content increased), helping to explain the in vitro release trends. Dye ingression and SVF dilution studies confirmed the increased hydrophilicity of the h-SEGs. h-SEGs have potential for use in vaginal drug delivery, particularly for ARV-based HIV-1 microbicides.

Sensitive bi-enzymatic biosensor based on polyphenoloxidases–gold nanoparticles–chitosan hybrid film–graphene doped carbon paste electrode for carbamates detection

A bi-enzymatic biosensor (LACC–TYR–AuNPs–CS/GPE) for carbamates was prepared in a single step by electrodeposition of a hybrid film onto a graphene doped carbon paste electrode (GPE). Graphene and the gold nanoparticles (AuNPs) were morphologically characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, dynamic light scattering and laser Doppler velocimetry. The electrodeposited hybrid film was composed of laccase (LACC), tyrosinase (TYR) and AuNPs entrapped in a chitosan (CS) polymeric matrix. Experimental parameters, namely graphene redox state, AuNPs:CS ratio, enzymes concentration, pH and inhibition time were evaluated. LACC–TYR–AuNPs–CS/GPE exhibited an improved Michaelis–Menten kinetic constant (26.9 ± 0.5 M) when compared with LACC–AuNPs–CS/GPE (37.8 ± 0.2 M) and TYR–AuNPs–CS/GPE (52.3 ± 0.4 M). Using 4-aminophenol as substrate at pH 5.5, the device presented wide linear ranges, low detection limits (1.68×10− 9 ± 1.18×10− 10 – 2.15×10− 7 ± 3.41×10− 9 M), high accuracy, sensitivity (1.13×106 ± 8.11×104 – 2.19×108 ± 2.51×107 %inhibition M− 1), repeatability (1.2–5.8% RSD), reproducibility (3.2–6.5% RSD) and stability (ca. twenty days) to determine carbaryl, formetanate hydrochloride, propoxur and ziram in citrus fruits based on their inhibitory capacity on the polyphenoloxidases activity. Recoveries at two fortified levels ranged from 93.8 ± 0.3% (lemon) to 97.8 ± 0.3% (orange). Glucose, citric acid and ascorbic acid do not interfere significantly in the electroanalysis. The proposed electroanalytical procedure can be a promising tool for food safety control.

Fabrication Of Potentiometric Sensors For The Determination Of Certain Metal Ions

In this study Fabrication of Potentiometric sensors for the determination of certain metal ions, presents the synthesis and characterization of seven ionophores, their use in the fabrication of potentiometric sensors and the results and discussion of fourteen sensors developed for the determination of five transition metal ions. As part of the present investigations a total of fourteen potentiometric sensors have been developed and fabricated. A three fold approach has been taken in developing he sensors, PVC plasticized membrane sensor, carbon paste electrode and chemically modified carbon paste electrode. All the sensors are highly useful in the determination of metal ions such as manganese, nickel, copper, mercury and lead. A through analytical study has been carried out with respect to each other developed. Based on these studies, optimum conditions have been developed for the quantitative determinations of the selected metal ions using the sensors. Systematic application studies have also been carried out for all the developed sensors and the results revealed that the presently developed sensors are far superior than most of the sensors reported.

Fabrication of Electrochemical Sensors for the Determination of Pharmaceuticals

Voltammetric sensors are an important class of electrochemical sensors in which the analytical information is obtained from the measurement of current obtained as a result of electrochemical oxidation/reduction.This current is proportional to the concentration of the analyte.Chemically modified electrodes(CMEs) have great significance as important analytical tools for the electrochemical determination of pharmaceuticals.The modification of electrode results in efficient determination of electro-active biomolecules at very lower potential without its major interferences.The operation mechanism of CMEs depends on the properties of the modifier materials that are used to promote selectivity towards the target analytes.Modified electrodes can be prepared by deposition of various compounds such as organic compounds ,conducting polymers,metal oxides,etc. on the various electrode surfaces.The thesis presents the development ,electrochemical characterization and analytical application studies of eight voltammetric sensors developed for six drugs viz.,Ambroxol,Sulfamethoxazole,PAM Chloride, Lamivudine,Metronidazole and Nimesulide.The modification techniques adopted as part of the present work include Multiwalled Carbon Nanotube(MWCNT) based modification.Electropolymerisation and Gold Nanoparticle (AuNP) based modifications.

Electrochemical studies on Metal phthalocyanines

The primary aim of these investigations was to probe the elecnuchemical and material science aspects of some selected metal phthalocyanines(MPcs).Metal phthalocyanines are characterised by a unique planar molecular structure. As a single class of compounds they have been the subject of ever increasing number of physicochemical and technological investigations. During the last two decades the literature on these compounds was flooded by an outpour of original publications and patents. Almost every branch of materials science has benefited by their application-swface coating, printing, electrophotography, photoelectrochemistry, electronics and medicine to name a few.The present study was confined to the electrical and electrochemical properties of cobalt, nickel, zinc. iron and copper phthalocyanines. The use of soluble Pes as corrosion inhibitor for aluminium was also investigated.In the introductory section of the thesis, the work done so far on MPcs is reviewed. In this review emphasis is given to their general methods of synthesis and the physicochemical properties.In phthalocyanine chemistry one of the formidable tasks is the isolation of singular species. In the second chapter the methods of synthesis and purification are presented with necessary experimental details.The studies on plasma modified films of CoPe, FePc, ZnPc. NiPc and CuPc are also presented.Modification of electron transfer process by such films for reversible redox systems is taken as the criterion to establish enhanced electrocatalytic activity.Metal phthalocyanines are p- type semiconductors and the conductivity is enhanced by doping with iodine. The effect of doping on the activation energy of the conduction process is evaluated by measuring the temperature dependent variation of conductivity. Effect of thennal treatment on iodine doped CoPc is investigated by DSC,magnetic susceptibility, IR, ESR and electronic spectra. The elecnucatalytic activity of such doped materials was probed by cyclic voltammetry.The electron transfer mediation characteristics of MPc films depend on the film thickness. The influence of reducing the effective thickness of the MPc film by dispersing it into a conductive polymeric matrix was investigated. Tetrasulphonated cobalt phthalocyanine (CoTSP) was electrostatically immobilised into polyaniline and poly(o-toluidine) under varied conditions.The studies on corrosion inhibition of aluminium by CoTSP and CuTSP and By virtue of their anionic character they are soluble in water and are strongly adsorbed on aluminium. Hence they can act as corrosion inhibitors. CoTSP is also known to catalyze the reduction of dioxygen.This reaction can accelerate the anodic dissolution of metal as a complementary reaction. The influence of these conflicting properties of CoTSP on the corrosion of aluminium was studied and compared with those of CuTSP.In the course of these investigations a number of gadgets like cell for measuring the electrical conductivity of solids under non-isothermal conditions, low power rf oscillator and a rotating disc electrode were fabricated.

Fabrication of Potentiometric Sensors for the Determination of Lanthanide Ions

In many fields such as earth science biology, environment and electronics, the knowledge about elemental distributions and chemical speciation is important. The determination of metal levels especially the toxic ones both in the environment and in biological materials are increasingly demanded by the society.Ion selective sensors have become one of the most effective ad powerful means for analytical scientists for the trace level monitoring of metal ions. The wide range of applications ,low material requirements and simplicity of analytical procedure have not only brought ion-selective electrodes in to the lime light of analytical chemistry,but have promoted their use as tools for physiologists,medical researchers,biologists,geologists,environmental protection specialists etc.Potentiometric ion-selective sensors have been developed for the determination of lanthanide ions such as La3+,Nd3+,Pr3+,Sm3+, and Gd3+.The sensors fabricated include both PVC membrane sensor and chemically modified carbon paste sensor. A set of 10 sensors have been developed. The response parameters of all the sensors have been studied and the sensors were applied as an indicator electrode in the potentiometric titration and for the determination of metal ions in real samples.

Development of Electrochemical Sensors for Various Pharmaceuticals

The development of electrochemical sensors is currently one of the active areas of research in analytical chemistry.Voltammetric sensors as an important class of electrochemical sensors are extensively used in pharmaceutical applications.In voltammetric analysis,many active compounds in dosage forms,in contrast to excipients,can be readily oxidised or reduced at the electrode surface by applying a potential.Chemically modified electrodes have great significance in the electrochemical determination of pharmaceuticals.The modification of electrode results in efficient determination of electroactive species at very lower potential without any major interferences.The present study involves the fabrication of 8 voltammetric sensors for the drugs Metronidazole Benzoate, Sulfamethoxazole, Acyclovir, Pam Chloride , Trimethoprim , Tamsulosin Hydrochloride and Ceftriaxone Sodium.Two sensors were developed for the drug tamsulosin hydrochloride while one sensor each was developed for the other drugs.

Electrochemical studies of tamsulosin hydrochloride using multiwalled carbon nanotube-modified glassy carbon sensor

A differential pulse voltammetric sensor for the determination of tamsulosin hydrochloride (TAM) using multiwalled carbon nanotubes (MWNTs)–Nafion-modified glassy carbon electrode (GCE) has been developed. MWNTs were dispersed in water with the help of Nafion and were used to modify the surface of GCE via solvent evaporation. At MWNT-modified electrode, TAM gave a well-defined oxidation peak at a potential of 1084 mV in 0.1 M acetate buffer solution of pH 5. Compared to the bare electrode, the peak current of TAM showed a marked increase and the peak potential showed a negative deviation. The determination conditions, such as the amount of MWNT–Nafion suspension, pH of the supporting electrolyte and scan rate, were optimised. Under optimum conditions, the oxidation peak current was proportional to the concentration of TAM in the range 1 × 1023 M–3 × 1027 M with a detection limit of 9.8 × 1028 M. The developed sensor showed good stability, selectivity and was successfully used for the determination of TAM in pharmaceutical formulations and urine samples

Electrocatalytic behavior of glassy carbon electrodes modified with multiwalled carbon nanotubes and cobalt phthalocyanine for selective analysis of dopamine in presence of ascorbic acid

This work describes the development, electrochemical characterization and utilization of a cobalt phthalocyanine modified carbon nanotube electrode for the quantitative determination of dopamine in 0.2 mol L-1 phosphate buffer contaminated with high concentration of ascorbic acid. The electrode surface was analyzed by cyclic voltammetry and electrochemical impedance spectroscopy which showed a modified surface presenting a charge transfer resistance of 500 Omega, against the 16.46 k Omega value found for the bare glassy carbon surface. A pseudo rate constant value of 5.4 x 10(-4) cm s(-1) for dopamine oxidation was calculated. Voltammetric experiments showed a shift of the peak potential of DA oxidation to less positive value at 390 mV as compared with that of a bare GC electrode at 570 mV. The electrochemical determination of dopamine, in presence of ascorbic acid in concentrations up to 0.1 mol L-1 by differential pulse voltarnmetry, yielded a detection limit as low as 2.56 x 10(-7) mol L-1.

An electrochemical sensor for (L)-dopa based on oxovanadium-salen thin film electrode applied flow injection system

An oxovanadium-salen complex (NAP-ethylene-bis(salicylidenciminato) oxovanadium) thin film deposited on a graphite-polyurethane electrode was investigated with regard to its potential use for detection of L-dopa in flow injection system. The oxovanadium(IV)/oxovanadium(V) redox couple of the modified electrode was found to mediate the L-dopa oxidation before its use in the FIA system. Experimental parameters, such as pH of the carrier solution, flow rate, sample volume injection and probable interferents were investigated. Under the optimized FIA conditions, the amperometric signal was linearly dependent on the L-dopa concentration over the range 1.0 x 10(-1) to 1.0 x 10(-4) mol L-1 (I-anodic, mu A) = 0.01 + 0.25 [L-dopa mu mol L-1]) with a detection limit (S/N = 3) of 8.0 x 10(-7) mol L-1 and a sampling frequency of 90 h(-1) was achieved. For a concentration of 1.0 x 10(-5) mol L-1 L-dopa, the R.S.D. of nine consecutive measurements was 3.7%. (c) 2006 Elsevier B.V. All rights reserved.

Electrochemical investigation of the dimeric oxo-bridged ruthenium complex in aqueous solution and its incorporation within a cation-exchange polymeric film on the electrode surface for electrocatalytic activity of hydrogen peroxide oxidation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Image analysis of modified cellulose fibers from sugarcane bagasse by zirconium oxychloride

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Electrochemical study of o-toluidine blue impregnated in mesoporous silica channels

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Voltammetric studies of titanium (IV) phosphate modified with copper hexacyanoferrate and electroanalytical determination of N-acetylcysteine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)