Solubility potentiometry

Since many new substances of interest are very poorly soluble in water, the assessment of the pKa in aqueous solution can be difficult and problematic. Potentiometry can be a quick technique for such assessment, provided the solubility of the substance is at least 100 pM. (Solutions as dilute as 10 pM can still be analyzed, but special attention must be given to electrode calibration, and ambient carbon dioxide must be excluded.) If the substance is soluble to only 1-10 pM and possesses a pH-sensitive UV chromophore, then spectrophotometry can be applied. CE methods may also be useful since very small sample quantities are required, and detection methods are generally quite sensitive. 

Potentiometry is used in the determination of various physicochemical quantities and for quantitative analysis based on measurements of the EMF of galvanic cells. By means of the potentiometric method it is possible to determine activity coefficients, pH values, dissociation constants and solubility products, the standard affinities of chemical reactions, in simple cases transport numbers, etc. In analytical chemistry, potentiometry is used for titrations or for direct determination of ion activities. 

In order to determine the stability constants for a series of complexes in solution, we must determine the concentrations of several species. Moreover, we must then solve a rather complex set of equations to evaluate the stability constants. There are several experimental techniques that are frequently employed for determining the concentrations of the complexes. For example, spectrophotometry, polarography, solubility measurements, or potentiometry may be used, but the choice of experimental method is based on the nature of the complexes being studied. Basically, however, we proceed as follows. A parameter is defined as the average number of bound ligands per metal ion, N, which is expressed as... 

To leam how the solubility constant, AT, can be measured potentiometri-cally. 

The ISEs described in this section are useful primarily for determination of halide ions by direct potentiometry, where the silver halide in the membrane is identical with the determinand. As follows from the discussion on p. 48 an electrode made of a less soluble silver halide X can be used to determine other halide Y" if the condition... 

In a related application, polyelectrolyte microgels based on crosslinked cationic poly(allyl amine) and anionic polyfmethacrylic acid-co-epoxypropyl methacrylate) were studied by potentiometry, conductometry and turbidimetry [349]. In their neutralized (salt) form, the microgels fully complexed with linear polyelectrolytes (poly(acrylic acid), poly(acrylic acid-co-acrylamide), and polystyrene sulfonate)) as if the gels were themselves linear. However, if an acid/base reaction occurs between the linear polymers and the gels, it appears that only the surfaces of the gels form complexes. Previous work has addressed the fundamental characteristics of these complexes [350, 351] and has shown preferential complexation of cationic polyelectrolytes with crosslinked car-boxymethyl cellulose versus linear CMC [350], The departure from the 1 1 stoichiometry with the non-neutralized microgels may be due to the collapsed nature of these networks which prevents penetration of water soluble polyelectrolyte. 

In essence there are three ways of determining these constants, namely, conductimetry 195,886), potentiometry 184, 289,887, 866), and the determination of the solubility of sparingly soluble metallic salts in presence of triphosphate (I48, 167, 335). 

The fluoride ion selective electrode is the most popular means of fluoride ion determination after sample destruction by any method but it does have limitations. It can be used either directly to measure the fluoride potential6 or as an end-point detector in a potentiometric titration with a lanthanum(l II) reagent as titrant.4,7 Problems can be experienced with potential drift in direct potentiometry, especially at low fluoride ion concentrations. Titration methods often yield sluggish end points unless water miscible solvents are used to decrease solubilities and increase potentia 1 breaks and sulfate and phosphate can interfere. End-point determination can be facilitated by using a computerized Gran plotting procedure.4... 

One significant reason why certain thermodynamic data are inadequate for equilibrium models is that they may not really be representative of equilibrium, having been obtained by experimental procedures (e.g., solubility or potentiometry) which were time-dependent in themselves and in which slow kinetics were involved. This is an aspect about which not much seems definitely known. 

Many methods including potentiometry, spectrophotometry, NMR spectroscopy, and reaction kinetics can be used to obtain Kn values in solution. Because ligands are often Arrhenius bases and metal-ligand complexes tend to be soluble in aqueous solution, potentiometric (pH) titration is one of the most widely used procedures. However, for complexes like [Ni(salpd)], where a non-aqueous medium is required, an alternative, spec-trophotometric method is preferred. As you will see when reading through the derivation, this method requires several criteria to be met. One of the most important is that one component, either [Ni(salpd)] or pyridine, must be in excess in our case this is pyridine. Another factor that will simplify the math is that pyridine does not absorb in the region of analysis. 

Potentiometry is a further technique used to measure aqueous solubility in discovery, although throughput limitations mean that this technique is used most often later in the LO stage. Potentiometric approaches specifically measure intrinsic solubility, which is the solubility of the neutral form of the molecule [38],... 

The pKa value is numerically equal to the pH value at which a molecule is half dissociated and the calculation or determination of the pK value(s) of a potential candidate drug should be one of the flrst physical properties determined. The approximate pK of the molecule of interest can be estimated by referring to literature values for substituents and similar molecules.A range of experimental techniques such as potentiometry, solubility determinations or ultraviolet-visible spectroscopy may be used for determination of the true pK value(s). 

Rosenberg LS, Wagenknecht DM. pKa determination of sparingly soluble compounds by difference potentiometry. Drug Dev Ind Pharm 1986 12 1449-1467. 

Unstable crystals, mp 119-120. Turns brown and liquefies on standing. The decompn products are formic acid and N-hydroxyglycine. Dibasic acid, potentiometrie titration shows pH peak at 3.5 and 9.1. Soluble in water, methanol, ethanol, acetone, ether... 

There are a number of different experimental methods to determine the stoichiometry and equilibrium constants for Reaction (V11.2). cf. Section Vll.3.4. The advantages and disadvantages of the most frequently used methods, potentiometry, liquid-liquid extraction and solubility, are briefly discussed in the following sections for more details see the book by Rossotti and Rossotti [1961ROS/ROS]. 

In the review of Baes and Mesmer [1976BAE/MES] an upper hmit of logj < -11.7 was calculated from the solubility data of [1964NAB/KUD] while Neck and Kim [2001NEC/KIM] selected an estimated value of logn, /3° = -(11 + 1) in their review. The present review does not recommend an equilibrium constant for the complex Th(OH)3 whieh is eonsidered to be a minor speeies in both potentiometrie and solubility studies. 

Direct Potentiometry Detemdnatiou of Hydrogen Chlonde Gas. A system has been described for the continuous monitoring of the HCl levels in gases or aerosols using a chloride-ion-selective electrode [IS]. This arose from a study on the loss of volatile decomposition products from poly(vinyl chloride) (PVQ and other chlorocarbon polymers in simulated fires. The method works well because of the excellent solubility of HQ in water, and the fact that the chloride electrode senses only free Q ion. Thus, other volatile chloride compounds will not be sensed. 

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