Ampholytes dissociation constants

Approximate Methods for Dissociation Constants.—Approximate, but more rapid, methods, similar to those used for simple monobasic acids and monoacid bases, have been frequently employed to determine dissociation constants of ampholytes. Upon taking logarithms, the equation for Ki may be written as... 

The dissociation constants, iCj (ratio of ampholyte to cation) and 1 2 (ratio of ampholyte to anion), are usually expressed logarithmically as pkTi and pX 2, where piC = - log K, in a manner analogous to the notation for pH. A is the pH at which equal quantities of the protonated (associated) and unprotonated (dissociated) forms are present. The isoelectric point, pi, is the pH where the molecules exist in the... 

From these equations, it is possible to predid the effective lipophilicity (log D) of an acidic or basic compound at any p H value. The data required to use the relationship in this way are the intrinsic lipophilicity (log P), the dissociation constant (piCa), and the pH of the aqueous phase. The overall outcome of these relationships is the effective lipophilicity of a compound, at physiological pH, which is approximately the logP value minus one unit of lipophilicity for every unit of pH, the pit, value is below (for acids) and above (for bases) pH 7.4. Obviously, for compounds with multifunctional ionizable groups, the relationship between log P and log D, as well as log D as a function ofpH, becomes more complex [62, 65, 67]. For diprotic molecules, there are already 12 different possible shapes of log D-pH plots. Ion pairs (salts), zwitterions, and ampholytes are special cases and both measurement of log P/D and their interpretation need special attention [44, 49]. 

The theory requires two assumptions that the dissociable groups may be divided into a small number of classes, each of which may be characterized by a single intrinsic dissociation constant (Kini)i and that the ampholyte may be represented as a sphere over Avhich the net charge is uniformly distributed. If n,- denotes the total number of groups of class i, and r< of these are dissociated at a given pH where the average net charge on the molecule is Z, then... 

We have shown in the section on hydrolysis included in the first chapter that the reaction of salts derived from weak acids and weak bases is never strongly acidic or strongly alkaline, unless the difference between the acidic and basic dissociation constants is too large. The same explanation, applied to the acidic and basic functions of ampholytes, accounts for the fact that solutions of amphoteric compounds never react very strongly acid or alkaline. 

For the sake of simplicity we shall refer to the undissociated ampholyte as A, to the ampholyte cations as A+, and to the anions as A. We shall designate the dissociation constant of the acidic group by Ka, the basic dissociation constant by Kb, and the constant of water by The total ampholyte concentration will be taken as equal to c. 

In order to illustrate the hybrid ion theory, we shall compare ammonium acetate with an amino acid of which the acid and basic dissociation constants are respectively the same as those of acetic acid and ammonium hydroxide. We know that in 0.1 molar solution, ammonium acetate is 0.5% hydrolyzed and the salt is 99.5% ionized. If we employ the same equation (40 in Chapter One) to calculate the degree of hydrolysis of the amino acid, we find that it too is 0.5% hydrolyzed. Thus it appears logical to assume that the remainder of the ampholyte is present in the ionogenic form. 

Ka and Kb are the true acidic and basic dissociation constants of the ampholyte whereas Ka and Kb are merely the apparent dissociation constants. 

A WApH titration method was used for the determination of acid dissociation constants (pK a values) of ionizable compounds. Microspeciation was investigated by three approaches ( ) selective monitoring of ionizable group by spectrophotometry, ( ) deductive method, and (3) K(z) method for determination of tautomeric ratio from co-solvent mixtures. It has been shown that the WApH technique, for such types of ampholytes, is able to deduce the microconstants and tautomeric ratios, which are in good agreement with the literature data. 

The amino acids are ampholytes, having both acid and basic properties. Their protolytic properties are best described by values (or pAg values), macroscopic dissociation constants for the acid groups involved. In Table II pA values are given for all the protein amino acids. The pAg values listed... 

Titrations of 0.0 lAf poly ampholyte in the presence of O.OIM nitric acid and ITif potassium nitrate were carried out vdth O.IAA potassium hydroxide solution. The dissociation constants were determined on the basis of the Henderson-Hasselbalch equation, as modified by Katchalsky and Spitnik [20], by measuring the pH as a function of the degree of neutralization a... 

Figure 5.32 shows the pH-pseudo-ftrst-order rate constant profile of the degradation of aspartame (an ampholyte, pKal = 3.19 and pKa2 = 8.14). In the hydrolysis of aspartame, the protonated/undissociated form predominates at low pH (<3), while the deprotonated/dissociated form exists at high pH (>8). As demonstrated for monoprotic weak acids and weak bases, certain terms in the numerator of Equation (5.173) become negligible. For example, the hydrolysis of the protonated/undissociated form by OH-, of the protonated/dissociated form by H+ and OH-, and the deprotonated/dissociated form by H+ are not likely to occur. Then, Equation (5.173) for the ampholytic drug is written as ... 

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