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Conductometric and indirect AAS determination of antimalarials.

Two methods are described for the determination of amodiaquine hydrochloride, chloroquine phosphate and primaquine phosphate, based on the formation of their ion-associates with [Cd(2+), Co(2+), Mn(2+) and Zn(2+)] thiocyanate, ammonium reineckate and/or sodium cobaltinitrite. The molar combining ratio reveal that (1:1) (drug:reagent) ion associates are formed for all reagents except for ammonium reineckate which form (1:2) ion associates with all studied drugs. The optimum conditions for the ion-association have been studied. Conductometric method was applied for the direct determination of the suggested drugs in bulk powders, whereas indirect atomic absorption spectrometric method, depending on the measurement of the excess metal ion present in supernatant solutions after precipitation of the ion associates is used to calculate the drug concentration. Optimum concentration ranges for the determination of aminoquinoline antimalarial drugs under consideration were 0.46-12.90 and 0.155-3.87 mg using conductometric and indirect atomic absorption spectral methods, respectively. The proposed procedures have been applied successfully to the analysis of these drugs in certain formulations and the results are favourably comparable to the official methods.

Antimalarials↗

Conductometric method for the quantitative analysis of Pb(II) and Cd(II) with 2-mercapto-5-R-amino-1, 3, 4-thiadiazole derivatives.

The reactions of the cations with 2-mercapto-5-R-amino-1,3,4-thiadiazole derivatives were studied conductometrically with the purpose of establishing a new conductometric method for the quantitative analysis of Pb(II) and Cd(II). Aqueous solutions of Pb(NO3)2 and Cd(CH3COO)2 were titrated with hidroalcoholic solutions of 2-mercapto-5-amino-1,3,4-thiadiazole (MATD), 2-mercapto-5-allylamino-1,3,4-thiadiazole (MA1ATD) and 2-mercapto-5-acetylamino-1,3,4-thiadiazole (MAcATD) and 2-mercapto-5-phenilamino-1,3,4-thiadiazole (MFATD) in different concentrations. The reactions takes place at pH 6.5 (realised with acetate buffer). A linear classical titration curves was obtained. In solutions more concentrated than 10(-2) M just one equivalence point can be noticed, corresponding to 1:2 Me:R stoechiometries. For concentration less than 10(-2) M two equivalence point were observed at 1:1 and 2:1 ratio of Me:R, indicating the step formation of the complex. Accurate conductometric determinations can be made using the second break points of the titration curves as equivalence points. The amounts of Cd(II) and Pb(II) taken and recovered are good, with an error less than 1%.

Cadmium↗

Alternating current aspects of antimicrobial molecular complexes.

A novel method was designed involving the titration of alternating current titration in a cell where one electrode was shielded by a capillary enclosure restricting access to it by charge carriers. With this cell, charge transfer complex titration of several thiazines all with some antimicrobial properties was effected in acetonitrile, against the electron accepting molecule iodine. The maxima of the Job plots generated by these titrations exhibited displacement of their positions for the forward and reverse titrations with respect to electron donor-acceptor complexation conductivity and apparent stoichiometry. A plot of inverse conductivity maxima differences against literature-cited dipole moments squared yielded a straight line passing through the origin. The titration plot profiles are discussed in terms of the type, number, and mobility of charge carriers produced in the complexation interaction. This novel method may be used to determine dipole moments of bioactive homologues empirically. There was correlation between thiazine drug dipole moments and minimal inhibitory concentrations of these drugs for some bacterial and yeast species. Several new avenues of investigation of possible relevance to microbiology are suggested.

Anti-Bacterial Agents↗

Charge transfer complexes of K vitamins with several classes of antimicrobials.

The charge transfer donor (D)-acceptor (A) complexes formed between three classes of vitamin K (all electron acceptors in this study) with several thiazine psychotropes, used also as antimicrobials, antimalarials, antibiotics, and anticoagulants, were studied by means of alternating current titrations. The monochloride thiazines formed 2:1 (D:A) complexes, interacting from 26 to 47.5%; the dihydrochloride formed a 3:1 (D:A) complex. The antimalarials quinine and its isomer quinidine yielded 2:1 (D:A) complexes, interacting 51 and 60%, respectively. Quinacrine did not complex with vitamin K. The antibiotics sulfisoxasole and sulfamethisole gave 1:1 complexes, respectively interacting 6.2 and 11.7%. The anticoagulants warfarin, coumarin and dicumarol, rather than forming complexes proceeded rapidly to chemical reaction. When the above thiazine antimicrobials, antimalarials and antibiotics are present in patients receiving vitamin K post-operatively the dosage of administered vitamin K should be increased to counteract the donor-acceptor interaction effect.

Anti-Bacterial Agents↗

Stability of polycationic complexes of an antisense oligonucleotide in rat small intestine homogenates.

Presystemic degradation in the gastrointestinal tract is one of the major problems contributing to the poor oral absorption of antisense oligonucleotides. Complexes between the antisense phosphorothioate oligodeoxynucleotide ISIS 2302 and the polycationic carriers protamine sulfate grade X, protamine chloride grade V, protamine phosphate grade X, poly-L-lysine hydrobromide (PLL), spermidine phosphate salt, spermine diphosphate salt, and Protasan G113 and CL113 were formulated in order to increase stability against intestinal nucleolytic degradation. Specific conductivity measurements were carried out to determine the charge ratio of the complex systems. Nuclease stability assays were performed in a rat small intestine homogenate model, which displayed significant exo- and endonuclease activity. Full-length oligonucleotide and metabolites were analyzed by capillary gel electrophoresis with UV detection at 260 nm. Most of the complexes of ISIS 2302 and the polycationic materials, except PLL-based systems, showed a better protection against enzymatic metabolism than free oligonucleotide. Protamine sulfate and protamine chloride considerably enhanced the nuclease stability of the phosphorothioate antisense oligonucleotide. The association of oligonucleotides with several polycationic substances proved to be an alternative to chemical modification in order to stabilize oligonucleotides in the gastrointestinal tract against nucleolytic degradation.

Animals↗

An ultrathin platinum film sensor to measure biomolecular binding.

A sensitive conductimetric immunosensor has been demonstrated based on an ultrathin platinum film on an oxidized silicon base. The film is about 25 A thick and is seen to consist of a discontinuous layer with channels 20-30 A wide. Monoclonal antibodies were bound to the sensor surface using conventional biosensor chemistry. Impedance at fixed frequencies across the film was used to track modification and binding at the surface. Impedance increased 55% at 20 Hz during the activation of the surface with anti-alkaline phosphatase (anti-AP). Binding of alkaline phosphatase (AP) to the prepared surface results in a further increase of 12%. p-Nitrophenyl phosphate hydrolysis confirmed binding and activity of the AP. About 40 amol AP were bound on the 0.5 cm(2) electrode. Non-specific binding of horseradish peroxidase caused an impedance change <6%. Control experiments showed small impedance changes and trace enzyme activity. Since the mechanism of electrical conduction of the thin film was not established, modeling of thin-film response was used to distinguish between redox processes, capacitance and tunneling mechanisms. The data fit well with the diffusion distributed elements (DE) model as well as a transmission line distribution element (DX) model. The first model, DE, is distributed elements for diffusion. The second DX model represents a transmission line. The sensors behave in a distributed network or like a transmission line.

Alkaline Phosphatase↗

Thermodynamics of substituted pyrazolone IX: potentiometric, spectrophotometric and conductometeric studies of 4-(4-chlorophenylazo)-3-methyl-1-[2-hydroxy-3-morphilinopropane 1-yl]-2-pyrazolin-5-one and its metal complexes.

The dissociation constants of 4-(4-chlorophenylazo)-3-methyl-1-[2-hydroxy-3-morphilinopropane-1-yl]-2-pyrazolin-5-one (CAMP) has been determined potentiometrically in 0.1 M KCl and 40% (v/v) ethanol-water mixture. The stepwise stability constants of the formed complexes of Mn2+, Co2+, Ni2+, Cu2+, Zn2+, La3+, Ce3+ and UO(2)2+, with CAMP have been determined. The stability of the formed complexes were found as follows: UO(2)2+ > Ce3+ > La3+ > Mn2+ < Co2+ < Ni2+ < Cu+ > Zn2+. The thermodynamic parameters (deltaG, deltaH and deltaS) for CAMP and its complexes were evaluated and discussed. The dissociation process is non-spontaneous, endothermic and entropically unfavourable. The formation of the complexes have been found to be spontaneous, exothermic or endothermic (depending on the metal) and entropically favourable. The stoichiometries of these complexes were determined spectrophotometrically and conductometrically and indicated the formation of 1:1 and 1:2 (metal:ligand) complexes.

Azo Compounds↗

A comparison of the levels of faecal indicator bacteria in water and human faeces in a rural area of a tropical developing country (Sierra Leone).

The levels of faecal coliforms (FC), indole-positive FC (presumptive Escherichia coli), faecal streptococci (FS), Streptococcus faecalis and Clostridium perfringens in the natural water sources used by 29 rural settlements in Sierra Leone were investigated. Levels of the same indicators in human faeces were also investigated. The incidence of Salmonella spp. in both habitats and the temperature, pH and conductivity of water sources were also recorded. All water sources were contaminated with the indicator bacteria, mean numbers of which occurred in the relationship FC greater than presumptive E. coli congruent to FS congruent to C. perfringens greater than S. faecalis. FC were also predominant in human faeces, the relationship of means being FC congruent to presumptive E. coli greater than FS greater S. faecalis greater than C. perfringens. The need for confirmation of FC counts obtained from water sources was indicated by the large number of positive tubes produced in the FC multiple-tube dilution test from some samples which could not be confirmed as presumptive E. coli. Salmonella spp. Were isolated from 13 water sources and 6% of faecal samples. Mean water temperature was high (26.2 degrees C), pH low (5.04) and conductivity low (34 microS cm-1). Presumptive E. coli was considered the most appropriate indicator of faecal pollution of the types of water investigated.

Bacteria↗

Use of ac admittance voltammetry to study very fast electron-transfer reactions. The [Ru(NH3)6]3+/2+ system in water.

The kinetics of electroreduction of Ru(NH3)6(3+) has been studied at a polycrystalline gold electrode using high-frequency ac admittance voltammetry. It is shown that precise kinetic data may be obtained for a very fast electron-transfer reaction using this technique. The kinetic data show a small double layer effect when the concentration of HClO4 used as background electrolyte is varied. This is discussed in terms of the point of zero charge, which is very close to the standard potential for the studied reaction.

Conductometry↗