Gwenola Burgot

Determination simultanee de l'enthalpie, de l'enthalpie libre via le coefficient de partage et de l'entropie de transfert eau/n-octanol de l'ephedrine par titrimetrie thermometrique

Abstract Thermometric titrimetry allows the simultaneous determination of the three thermodynamic parameters of transfer (Δ G 0 T , Δ H 0 T and Δ S 0 T ) of ephedrine from water to n -octanol. Principle, methods, results and discussion are given.

Thermodynamics of partitioning in the n-octanol/water system of some β-blockers

Abstract It is possible to obtain by therrnometric titrimetry the water/ n -octanol transfer enthalpy of a series of β-blockers. The transfer entropy can be assessed by combining these results with the corresponding values of the partition coefficients determined independently. The results obtained are discussed according to the pharmacological properties of these substances.

Determination of Entacapone by Differential Pulse Polarography in Pharmaceutical Formulation

Abstract The electrochemical methods, sampled direct current, and differential pulse polarography, were developed successfully and applied to the routine determination of Entacapone in pharmaceutical formulation. Both methods gave rise to three reduction waves or peaks respectively. The irreversibility and the diffusion‐controlled of the first reduction were confirmed by cyclic voltammetry. The limiting currents are directly proportional to the concentration of entacapone with a correlation coefficient of 0.99. The within‐day coefficients of variation and the day‐to‐day coefficient of variation were less than 3.5% for entacapone and Comtan®. The percentage recovery for entacapone in tablets is satisfactory for both methods. The method is simple without any pretreatment.

log P Estimation of 1,2-Dithiole-3-thiones and 1,2-Dithiole-3-ones: A Comparison of Experimental and Calculative Approaches

PurposeTo 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.MethodsExperimental 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.ResultsQuality of calculations significantly differs depending on the subset under consideration. For database compounds 01–48, comprising alkyl and aryl substitution in 4- and 5-position, the fragmental methods ACD/log P, CLOGP, and KOWWIN perform significantly better than the atom-based approach XLOGP and the whole-molecule method QLOGP. For database compounds 49–68, comprising formyl and acyl substitution in 4- and 5-position, superiority of the whole-molecule method QLOGP over the substructure-based approaches is observed. The strong underestimation of log P for compounds 49–68 probably indicates hidden physicochemical phenomena resulting from the juxtaposition of the acyl and dithiole moieties.ConclusionsAll calculation methods included in this study need a thorough refinement to adequately cope with particular solvation behavior suspected to prevail in formyl- or acyl-DTT and DTO, which represent a chemical class of high pharmacological interest.

First relationships between detoxication properties of some 1,2-dithiole-3-thiones and their log P

First quantitative structure-activity relationships (QSAR) between electrophile detoxication properties of 1,2-dithiole-3-thiones and their log P values were checked. A very significant linear property was found with some disubstituted derivatives. In all cases, it was found that the less lipophilic dithiolethiones were the most active.

Principe de l'estimation par titrimétrie thermométrique de l'enthalpie et de l'entropie de transfert eau/n-octanol de solutes très lipophiles

Abstract Titrimetric thermometry allows estimation of the enthalpy of transfer of very lipophilic solutes from water to n-octanol. Combining these values with those of the corresponding transfer coefficients obtained independently gives an estimation of the entropy of transfer. A number of examples are given.

A first estimation of the thermodynamic parameters of water/n-octanol partitioning of some tricyclic antidepressants: Similarities and differences with the values of other psychotropic drugs

Abstract Thermometric titrimetry allows the determination of the thermodynamic parameters of transfer from water to n -octanol for tricyclic antidepressants. Their transfers are both entropy and enthalpy driven, whereas those of phenothiazinic neuroleptics are solely entropy driven. The hypothesis of the folding of the lateral chain upon the tricyclic nucleus in antidepressive drugs gives a satisfactory explanation of the results. Differences and analogies of behavior during the partitioning of antidepressants and phenothiazinic compounds are also underlined.

Determination simultanee de l'enthalpie, du coefficient de partage et de l'entropie de transfert EAU/n-octanol de l'ephedrine par titrimetrie thermometrique: aspects cinetiques

Abstract The kinetics of the thermometric titration of ephedrine by an aqueous solution of a strong acid in the presence of n-octanol are studied. The theory is tested at different experimental conditions. The importance of some parameters is outlined and a practical limit beyond which the kinetics of the transfer must be taken into account is defined.

Water/n-octanol thermodynamic parameters of some phenothiazines

Abstract Thermometric titrimetry allows the determination of the water/ n -octanol transfer enthalpies of a series of phenothiazines. By combining these results with the corresponding average values of the partition coefficient determined independently, their transfer entropies can be assessed. The transfer enthalpies of the series studied are significantly more endothermic for the compounds endowed with major neuroleptic activity.

Elimination of linear parameters in non-linear regressions : a fast and effective method for the determination of binding parameters

Abstract A semi-linear least-squares regression methodology is proposed to extract binding parameters from experimental binding data. After legitimation of simplification and suitable mathematical transformation, the only non-linear parameter which remains to be searched for by a non-linear least-squares regression is the affinity constant. As a result, number of sites and affinity constants are easier to grasp than with a full non-linear regression. This methodology can be applied to saturation as well as to displacement binding studies. It has been tested with binding data of QNB and aBTX on rat hippocampus synaptosomes.