Potentiometric method, measurement compounds

Liu, X., Bouchard, G., Girault, H.H., Testa, B. and Carrupt, P.A. (2003) Partition coefficients of ionizable compounds in o-nitrophenyl octyl ether/ water measured by the potentiometric method. Analytical Chemistry, 75, 7036-7039. 

Contrary to potentiometric methods that operate under null current conditions, other electrochemical methods impose an external energy source on the sample to induce chemical reactions that would not otherwise spontaneously occur. It is thus possible to measure all sorts of ions and organic compounds that can either be reduced or oxidised electrochemically. Polarography, the best known of voltammetric methods, is still a competitive technique for certain determinations, even though it is outclassed in its present form. It is sometimes an alternative to atomic absorption methods. A second group of methods, such as coulometry, is based on constant current. Electrochemical sensors and their use as chromatographic detectors open new areas of application for this arsenal of techniques. 

The polarographic and potentiometric methods are not HPLC-run. The polarographic method relies upon the measurement of half-wave potentials of various sulfur compounds reacting with a mercury electrode. It is sensitive to submicromolar concentrations (Luther, pers. com.). While sulfide, thiosulfate, polysulfide and polythionates can be measured, the initial sample must be subdivided and pretreated in different ways. The disadvantages are that sample preparation ana analysis are time-consuming and there is no way to preserve samples for later analysis nor to study organic thiols with precision., ... 

With the potentiometric approach, determination of intrinsic solubility is based upon the measurement of the pH shift caused by compound precipitation during acid-base titration of ionizable compounds. Two commercial potentiometric methods currently available are pSol [30, 39] and Cheqsol [40-42], In the pSol method developed by Avdeef, a minimum of three titrations in the direction of dissolution are performed. Normal pH versus volume titration plots are reexpressed as Bjerrum plots, that is, average number of bound protons versus pH. The Bjermm plots enable the shift in compound pKa to be more readily observed and are used to determine intrinsic solubility (S0) via Equation 2.5 ... 

Provided that the other precautions commonly employed in analyses by spectrophotometry are observed, and that the spectral characteristics of the compound are favourable, results of high accuracy can be expected if a constant temperature is employed for both the pH and the optical density measurements. Jacketed cell holders which can be connected to a thermostatically controlled bath are commercially available for this purpose. If a pH meter is used in the preparation of the buffer solutions, the precision of the method will be determined largely by its performance. Similarly the accuracy of the results will be a function of the accuracy with which it is possible to use a glass electrode, and the same limitations will apply to this method as to the potentiometric method (see p. 38). 

Base line 3 is drawn extrapolating to a value of AH (a= 1) of —7.85 kcal mole obtained by potentiometric measurements at different temperatures on the model compound mentioned above. This extrapolation leads to 2i AH of 1.07 kcal residue" The values of AH obtained by microcalorimetry have to be compared with the value of 1.16 kcal residue" obtained by the temperature dependence of potentiometric data. Taking into account the errors connected with the potentiometric method, the errors of the calorimetric one (essentially due to the uncertain choice of the baseline) and the possible difference between AH and AHc, the agreement between the two sets of data is rather good indeed. This fact is most gratifying in view of the eventually large, unexplained. 

However, there is still a strong need to develop new methods that will be able to quantitatively or at least qualitatively estimate the prediction accuracy of log D models. Such models will allow the computational chemist to distinguish reliable versus nonreliable predictions and to decide whether the available model is sufficiently accurate or whether experimental measurements should be provided. For example, when applying ALOGPS in the LIB RARY model it was possible to predict more than 50% and 30% compounds with an accuracy of MAE <0.35 for Pfizer and AstraZeneca collections, respectively [117]. This precision approximately corresponds to the experimental accuracy, s=0.4, of potentiometric lipophilicity determinations [15], Thus, depending on the required precision, one could skip experimental measurements for some of the accurately predicted compounds. 

However, solvation and entropy (which could be very different between these two types of amines) must be taken into account when comparing the two methods (titration and infrared spectroscopy). The ionization constants of a series of silylmethylpiperidines and their carbon analogs were measured potentiometric ally in methanol. The data indicates a lower basicity for these compounds, compared to non-silylated analogs, which was explained in terms of inductive effects, three-center-bond formation and (p-d)cr interactions.26 From a study of the effect of solvation by acetone on the basicity of... 

Thermodynamic functions (entropy, heat capacity, enthalpy and free energy functions) have not been reported for 1,2,4-thiadiazoles. The ionization constants of a number of 1,2,4-thiadiazoIes have been determined potentiometrically or by Hammett s method (65AHC(5)ll9). Polarographic measurements of a series of methylated 5-amino-l,2,4-thiadiazoles show that thiadiazoles are not reducible in methanolic lithium chloride solution, while thiadiazolines are uniformly reduced at E0.s = -1.6 0.02 V. This technique has been used to assign structures to compounds which may exist theoretically as either thiadiazoles or thiadiazolines (65AHC(5)119). 

The determination of ascorbic acid in foods is based, in part, on its ability to be oxidized or to act as a reducing agent. The most common method for determination of vitamin C in foods is the visual titration of the reduced form with 2,6-dichloroindophenol (DCIP) (4-7). Variations in this procedure include the use of a potentiometric titration (6), or a photometric adaptation (S) to reduce the diflSculty of visually determining the endpoint in a colored extract. The major criticisms of this technique are that only the reduced vitamin, and not the total vitamin C content of the food, is measured, and that there can be interference from other reducing agents, such as sulfhydryl compounds, reductones, and reduced metals (Fe, Sn, Cu), often present in foods. The DCIP assay can be modified to minimize the effects of the interfering basic substances, but the measurement is still only of the reduced form. Egberg et al. (9) adapted the photometric DCIP assay to an automated procedure for continuous analysis of vitamin C in food extracts. 

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