Validation of a new method using the reactivity of electrogenerated superoxide radical in the antioxidant capacity determination of flavonoids.

This article lays out a new method to measure the antioxidant capacity of some flavonoids. The methodology developed is based on the kinetics of the reaction of the antioxidant substrate with the superoxide radical (O(2)(*-)). A cyclic voltammetric technique was used to generate O(2)(*-) by reduction of molecular oxygen in aprotic media.

log P estimation of 1,2-dithiole-3-thiones and 1,2-dithiole-3-ones: a comparison of experimental and calculative approaches.

Purpose: To estimate experimental log P values of formerly described 5-formyl- and 5-acyl-dithiole-3-thiones (DTT) and -dithiole-3-ones (DTO) and to check the validity of five log P calculation programs via experimental log P for a database of 68 DTT and DTO.

Methods: Experimental log P values were measured by means of octanol/water partitioning; for determining solute concentrations in water, RP-HPLC with spectrophotometric detection was used. For calculating log P, the fragmental methods ACD/log P, CLOGP, and KOWWIN, the atom-based approach XLOGP, and the whole-molecule approach QLOGP were applied.

Spray-dried redispersible oil-in-water emulsion to improve oral bioavailability of poorly soluble drugs.

A physically stabilized dry emulsion dosage form reforming the original emulsion after rehydration was developed by spray-drying a liquid oil-in-water emulsion containing maltodextrin as carrier and sodium caseinate as emulsifying agent. Several oil:water as well as maltodextrin:water ratios were tested, the homogenization and spray-drying processes and the reconstitution properties were investigated and an optimum formulation was selected for poorly soluble drug incorporation, having an identical oil:water and carrier:water ratio of 10% (w/w) and a load of solid material of 20% (w/w). Lipophilic 5-phenyl-1,2-dithiole-3-thione (5-PDTT) was selected as a model drug.

[Which species actually exist in relation with time and pH when compounds exhibit several dissociation and kinetic constants: the striking case of a thieno-1,4-diazepine].

A solution of a molecule having several dissociation and kinetic constants evolves with time and pH-value. Now it is important from a pharmacological standpoint to know which species actually exist in solution. The knowledge of the kinetic and dissociation constants allows to plot the concentrations profiles versus time and versus pH-values of the whole protolytes.

Protometric thermometric titrations of sparingly soluble compounds in water in the presence of n-octanol.

Thermometric titrimetry permits titration of acido-basic compounds in water in the presence of n-octanol. n-Octanol permits the solubilization of protolytes and moreover may also displace the equilibria of the titration reactions. Hydrochlorides of highly insoluble derivatives such as phenothiazine derivatives can be titrated with satisfactory accuracy and precision by sodium hydroxide despite their high pK(a) values.

On the reduction of dithiolethiones and dithiolylium ions by NADPH and glutathione reductase.

Results of in vitro experiments carried out in water at 25 degrees C and at pH 7.56 proved that NADPH in the presence of yeast glutathione reductase did not react with 1,2-dithiole-3-thiones and 1,2-dithiole-3-ones. On the other hand, 3-methylthiodithiolylium ions did react in these conditions.

[Rigorous algorithms for calculating the exact concentrations and activity levels of all the different species during acid-base titrations in water].

The principles of two algorithms allowing the calculations of the concentration and activity levels of the different species during acid-base titrations in water are described. They simulate titrations at constant and variable ionic strengths respectively. They are designed so acid and base strengths, their concentrations and the titrant volume added can be chosen freely.

Biopharmaceutics and pharmacokinetics of 5-phenyl-1, 2-dithiole-3-thione complexed with sulfobutyl ether-7-beta-cyclodextrin in rabbits.

The biopharmaceutics and pharmacokinetics of 5-phenyl-1, 2-dithiole-3-thione (5PDTT) were investigated in rabbits, after administration as a complex with sulfobutyl-ether-7-beta-cyclodextrin (SBE7-beta-CD) by intravenous and oral routes and as a micronized powder by oral route. 5PDTT had a rapid and large red blood cell partitioning that was not dependent on drug concentration either in vitro or ex vivo. The blood clearance was very high (354 +/- 131 mL/min) suggesting extrahepatic metabolism and/or nonrenal elimination and a significant volume of distribution (67 +/- 76 L).

Improvement in solubility and dissolution rate of 1, 2-dithiole-3-thiones upon complexation with beta-cyclodextrin and its hydroxypropyl and sulfobutyl ether-7 derivatives.

Inclusion complexes between beta-cyclodextrin derivatives and 1, 2-dithione-3-thiones were studied in aqueous solution and in the solid state. Phase solubility study was used to evaluate the complexation in solution, at 37 degrees C, of three cyclodextrins, i. e.

Correlations between n-octanol/water partition coefficients and RP-HPLC capacity factors of 1,2-dithiole-3-thiones and 1,2-dithiol-3-ones.

From the experimental n-octanol/water partition coefficients (log Poct) of 33 1,2-dithiole-3-thiones and 18 1,2-dithiol-3-ones and their respective log k, Collander-type relationships were established at various volume fractions of methanol in the mobile phase and on an ODS 2 stationary phase. Collander-type relationships were also established between log Poct and log K0 (capacity factor extrapolated to 0% of organic modifier). The correlations are good, and their parameters depend on the volume fraction of organic modifier, as expected.

Ionization constants of ginkgolide B in aqueous solution.

The thermodynamic ionization constants (pK(a)(1), pK(a)(2), and pK(a)(3)) of ginkgolide B (9H-1,7a-(epoxymethano)-1H,6aH-cyclopenta[c]furo[2,3-b]furo-[3',2':3,4]cyclopenta[1,2-d]furan-5,9,12-(4H)-trione, 3-tert-butylhexahydro-4,7b,11-trihydroxy-8-methyl-) in aqueous solution have been settled by pH-metric and NMR studies. The three macroscopic pK(a) values as well as the water solubility and the water/n-octanol partition coefficient have been extracted from pH-metric data by means of a nonlinear regression methodology. NMR spectroscopy provided confirmation of the values of the macroscopic constants, information about the effective ionization pathways, and an estimation of the proportions of the various forms under physiologically relevant conditions.

Water/n-octanol partition coefficients of 1,2-dithiole-3-thiones.

Water/n-octanol partition coefficients (log P) for 33 1,2-dithiole-3-thiones and for 18 1,2-dithiol-3-ones were determined by RP-HPLC measurement of the concentration of the solute in aqueous solution after equilibrium. Depending on the nature of the substituents (alkyl or aryl) and their position(s) (4,5, or both) on the dithiole nucleus, some peculiar behaviors were revealed. Therefore, different fragmental constants containing the 1,2-dithiole-3-thione nucleus were inferred in order to calculate in a complementary work, a priori, the log P values of new dithiolethiones and dithiolones.

A new pH-metric methodology for the determination of thermodynamic inclusion constants of guest/cyclodextrin complexes.

A new methodology of pH-metric data treatment was developed to extract the stoichiometry and the thermodynamic association constants of guest-cyclodextrin inclusion complexes in dilute aqueous solution when the guest is a participant in an acid-base equilibrium. pH-metric titration curves in the presence of cyclodextrin (CD) were treated by a curve-fitting technique according to a nonlinear least-squares regression. Equations corresponding to the different kinds of acid-base pairs (AH/A-, BH+/B) and stoichiometries (1:1 and 1:2) were established.

[Determination by thermometric titrimetry of the thermodynamic parameters of water/n-octanol transfer of several non-steroidal anti-inflammatory drugs].

The calorimetric determination by thermometric titrimetry of the water/n-octanol transfer enthalpies of some non steroidic anti-inflammatory compounds is described. By combining the values obtained with that of the free enthalpies of transfer issuing from the values of corresponding log P, it is possible to determinate the transfer entropies of the solutes. The whole results of the show that almost the transfers are both enthalpy and entropy driven.

[Chemical potentials of solutes and quantitative structure-activity relationships: study in a series of barbiturates].

The part, displayed by the solvatation of the solute in 2 solvents with witch log P is determined, is studied by 2 indirect process. They consist to test some QSAR where the corresponding chemical potentials are effective but with different weighs than in log P. The results obtained with barbiturics confirm the importance of the couple water/n-octanol and show that taking account of two partitionning process can improve the significativity of the QSAR.

[Preparation and schistosomicidal activity of vinylogues of 1,3-dithio-3-thione].

The synthesis of vinylogues of 1,2-dithiol-3-thione is described. The activity in experimental schistosomiasis (schistosomicidal activity and, for the most interesting ones, on the egg-laying) was tested in mice with Schistosoma mansoni in comparison with oltipraz.

[Not Available].

The reversibility of the determination reaction is the most frequent cause of deviations from linearity of thermometric titration curves. Because of this, determination of the equivalence point by the tangent method is associated with a systematic error. The authors propose a relationship which connects this error quantitatively with the equilibrium constant.

[Not Available].

The variation in heat capacity and the thermal shifts which accompany a thermometric determination make the thermogram, even in the case of a very rapid and irreversible reaction, hyperbolic instead of formed of straight segments. These departures from linearity, which are inconvenient in the interpretation and exploitation of the thermograms, can be calculated as a function of the degree of titration. The relation obtained introduces a parameter which the authors call the apparent change of capacity at the equivalence point, and which takes into account the two causes of deviation from linearity.

[Not Available].

Acids conjugated to various phenothiazine derivatives are titrated directly with sodium hydroxide, by means of an automatic thermometric titrimeter. The titration curves have sharp breaks, suitable for analytical use, and these are discussed, in the case of promethazine hydrochloride, as functions of various parameters such as pK(a), the solubility of the product and the enthalpy of neutralization (determined in this work).

[Not Available].

Maleic, fumaric, tartaric, glutaric and adipic acids are titrated directly with sodium hydroxide by means of an automatic thermometric titrimeter. The titration curves have two break-points, corresponding to the successive neutralization of the two acid groups. Previous standardization permits measurement of the heats of neutralization, from which the enthalpies of dissociation can be deduced.