Ionization constant, pKa

Most drugs are ionized in aqueous solution (Table 2.1), and can therefore exist in a neutral or a charged state, depending on the pH of the local environment. Molecules are more lipophilic when neutral than when charged. Ionization is expressed by the aqueous ionization constant, pKa. As pointed out below, log D is a p Independent term for ionizable drugs. Permeability and aqueous solubility are also pKa-dependent. Lipophilicity, pKa, permeability through artificial membranes and... 

The value of its ionization constant (pKa =5.01) approximates that of acetic acid. 

For polyelectrolyte, in general, the following relationship is given in the degree of ionization, a, and the apparent ionization constant, pKa, which is popularly called the modified Henderson-Hasselbach equation (51). 

IONIZATION CONSTANTS, pKa, DKb, AND pi VALUES OF SOME COMMON AMINO ACIDS ... 

Schultz, T.W. (1987a). The Use of the Ionization Constant (pKa) in Selecting Models of Toxicity in Phenols. Ecotox.Environ.Safe., 14,178-183. 

The acid ionization constant (pKa) of the aqua complex ion determines whether or not the ion would form complexes with a protein. This depends greatly on the pH of the medium. Since the ionization constant of low charge is 12.6, the ion would form a stable complex only with negatively charged protein in alkaline media. It cannot bind to cationic proteins because it does not share electrons to form a covalent bond. This consideration explains why the activity of Ca2+-activated protease is optimum in the alkaline pH range. Thus a decrease in its activity at acidic pH values may partly be due to a change in the electronic state of Ca2+ (Asghar and Bhatti, 1987 Barbut and Mittal, 1985). 

Ageneraiized, weighted, noniinear ieast squares procedure is deveioped, based on pH titration data, for the refinement of octanoi-water partition coefficients (iog P) and ionization constants (pKa) of multiprotic substances. Ion-pair partition reactions, self-association reactions forming oligomers, and formations of mixed-substance complexes can be treated with this procedure. The procedure allows for CO2 corrections in instances where the base titrant may have CO2 as an impurity. Optionally, the substance purity and the titrant strength may be treated as adjustable parameters. The partial differentiation in the Gauss-Newton refinement procedure is based on newly derived analytical expressions. The new procedure was experimentally demonstrated with benzoic acid, 1-benzylimidazole, (+)-propranolol, and mellitic acid (benzenehexacarboxylic acid, AH6). 

TABLE 12.2 The Ionization Constants (pKa) of each of the 20 Natural Amino Acids... 

Ionization constants (pKa) and thermodynamic parameters were determined for selenazolidine diones (175 R=Me2N,Me0,H,Cl,N02) in DMF. Linear correlations were obtained with = -1.62,-1.55, and -1.44 at 298,308 and 323 K, respectively22. I.R. spectra for (176), its trideuterated analogue, and potassium salt were reported. The vibrational frequencies recorded were almost identical to those of thiazolidinones. Additionally, the structure of (176) was examined by X-ray crystallography . Diazotisation of 2-amino-1,3-selenazole (177) with NOBF /NaF/HBF affords (178) and (179) in 17% and 26%, respectively, presumably via the diazonium ion. This is reportedly the first successful Sandmeyer-Schiemann... 

The reported acid ionization constant (pKa) of estrone shows great variation ranging from 9.36 to 11.0 (132,133). Previous methods of measurement included back titration, conductimetric and most recently U.V. spectrophotometric. Recent work (99,134) places the pJCa between 10.34 and 10.914. The most recent spectrophotometric determination (135) reported the pKa to be 10.77 0.02 with seven determinations."... 

The ionization constant, pKa, was obtained by measuring the pH of buffered solutions of chloral hydrate9D. The mean of 25 experiments gave pKa n 10.Oil, which differs considerably from the value of 11 obtained by Euler and Euler 97 and is closer to pK n 9.77, derived indirectly... 

These two parameters are intimately involved with each other particularly in the charged state. Hydrophobicity, as measured by log P, refers to the partitioning of a solute that remains neutral over the pH range in question, while log D (distribution coefficient or apparent log P) constitutes a measure of the partitioning of both the neutral and charged species of a compound at a particular pH. Thus log D is related to log P via the ionization constant, pKa. 

In addition to the electronic (o), steric (Es) and hydrophobic (it) descriptors (Table 11.12), other physical and chemical descriptors such as electronic descriptors (e.g. ionization constants pKa, NMR chemical shifts 8) steric descriptors (e.g. molar volume MV, van der Waals volume V, molar refractivity MR, parachor P,), hydrophobic descriptors (e.g. distribution coefficient logD, solubilty parameter logS), property descriptors (e.g. T of DNA) and theoretical parameters (e.g. atomic charge q°or q", electrostatic potential V(r)) are also employed in the QSAR studies of chemical and biological systems. 

Oral absorption Solubility Permeability Ionization constant (pKa)... 

The CP of the IMP solutions has been found highly sensitive to the solution pH (see Figure 9). The results show that the CP decreases as the value of pH increases (whether or not an electrolyte is present). In the pH range employed, this decrease in the CP is due to changes in the micellar surface charge. The ionization constant, pKa, of IMP in free molecular state is... 

Ionization constants (pKa) and thermodynamic parameters were determined for selenazolidine diones (175 R=Me2N,Me0,H,Cl,N02) in DMF. Linear correlations were obtained with =-1.62,-1.55, and at 298,308 and 323 K, respectively. I.R. spectra... 

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