Dissociation constant approximate method

Dissociation Constants. Numerous methods can be used for the determination of dissociation constants, and there are often differences in the various values reported in the scientific literature. The pK values given in the monographs have been taken from published data and should be regarded only as approximate. The temperature at which the determination was made is given where known. Information on the theory, measurement, and evaluation of dissociation constants is given in The Pharmaceutical Codex, 11th Edn, London, The Pharmaceutical Press, 1979. 

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... 

Three experimental methods that are capable of determining dissociation constants with a precision of the order of tenths of 1% have been most commonly used. Each of these methods—the cell potential method (2), the conductance method (3), and the optical method (4)—provides data that can be treated approximately, assuming that the solutions obey Henry s law, or more exactly on the basis of the methods developed in Chapter 19. We will apply the more exact procedures. As the optical method can be used only if the acid and conjugate base show substantial differences in absorption of visible or ultraviolet light, or differences in raman scattering or with the use of indicators, we shall limit our discussion to the two electrical methods. 

The plot of the pH-dependence (Fig. 18) indicates qualitatively a participation of an intermediate acid-base equilibrium. Evaluation of rate constants kr and kg is made difficult by the inaccessibility of the dissociation constant of reaction (24 b) which corresponds to protonation of a radical anion. ESR would be a suitable method for the determination of the dissociation constants of at least the more stable radical anions. Another possibility for obtaining at least an approximate value of the equilibrium constant is the measurement of the shifts of the half-wave potentials of the more negative wave at potential 3 with pH. Because the half-wave potential of this wave is known to be sensitive to the... 

There are three NMR-based approaches suitable to propose the bioactive conformation of ligands in the absence of the coordinates of the whole complex 1. conformation analysis of free ligand in solution has a high chance to find with some population the bound conformation, although it may be solvent dependent (refer to Sect. 2.2.2) 2. determination of bound ligand conformation by means of transferred NMR methods if the dissociation constant is not smaller than approximately 50 pM (refer to Sects. 2.1 and 2.3) 3. solid-state NMR of the complex if the ligand can be obtained with 13C labels (Sect. 2.2.3). 

To initialize the numerical method, they find an approximate solution using the bulk dissociation constant, (Kd), the effective dissociation constant representative of the population as a whole. (Kd) is directly measurable. For theoretical purposes, they estimate (Kd> using the reciprocal of the average affinity of the population ... 

Approximate Methods for Bases.—The procedures described for determining the dissociation constants of acids can also be applied, in principle, to bases analogous equations are applicable except that hydroxyl ions replace hydrogen ions, and vice versa, in all the expressions. Since the value of the product of an and ooir is known to have a definite value at every temperature (cf. Table LXI), it is possible to derive ooh" from obtained experimentally. 

If the color of the base B differs from that of its conjugate acid BH+, it is possible by light absorption experiments to estimate the value of either cb or Cbh since the stoichiometric composition of the solution is known, the concentrations of all the four species cha, Ca", Cb and Cbh can be thus estimated, and value of K in equation (36), apart from the activity coefficient factor, can be calculated. In this way the approximate ratio of the dissociation constant of the acid HA to that of BH+ is obtained. The procedure is now repeated with an acid HA using the same base B, and from the two values of K the ratio of the dissociation constants of HA and HA can be found. This method can be carried through for a number of acids, new bases being used as the series is extended. ... 

V. Dissociation Constant Method.—All the methods described above give approximate values only of the so-called hydrolysis constantof the salt the most accurate method for obtaining the true hydrolysis constant is to make use of the thermodynamic dissociation constants of the weak acid or base, or both, and the ionic product of water. For this... 

It is generally assumed that measurements with the hydrogen electrode yield the hydrogen ion activity. That this is only approximately true can be seen from the discussion of the potentiometric method of determining dissociation constants (cf. pages 75 and 76). 

A general method for estimating dissociation values, given a set of solubility and pH measurements for tyrosine and 2,8-dihydroxyadenine, is presented. Equations are derived extending solubility, pH and dissociation constant relationships from weak acids and bases to polyprotic, amphoteric compounds. Included in ttie estimation procedure is a subroutine for approximating ttiermodynamic dissociation constants."... 

Kambe et al. [23] determined the dissociation constants of some furfurylidene-jP-nitrophenylhydrazones by plotting appropriate absorbance values versus pH. The pKi and pK2 of p-hydroxybenzoic acid have been found to be 4.61 and 9.31 by a spectrophotometric method [24]. Since the equations employ concentration instead of activity, the experimental results for pK values are approximate unless corrected for activity. 

The conductance method is satisfactory only if the solvent can be rigorously purified. Through failure to appreciate this, the first values of pKa of picric acid in acetonitrile proved to be much too small, 5.6 and 8.9 as compared with 11.0 from electromotive force measurements on buffered solutions. D Aprano and Fuoss found that acetonitrile having a satisfactory specific conductance of about 10 cm still contained a trace of ammonia. This was converted to ammonium pic-rate when acid was added to the solvent giving a spurious contribution to the conductance of picric acid solutions. This discovery moved them to make the flat assertion that dissociation constants of weak acids cannot be determined in aprotic solvents conductimetrically . This may be an overly pessimistic view, conductance values of pKa for acids in di-methylsulphoxide and dimethylformamide agree well with those from spectrophotometric and electromotive force measurements. Approximate values of pKa and pKf can be obtained from conductometric titrations of a weak acid with a weak base. ... 

The most important reaction property is the rate constant. Unfortunately, there is no method known yet that can predict this property, except for an approximate method for the dissociation constant. The other properties directly relevant to reaction are the heat of combustion, and the heat, entropy, and free energy of formation. 

Because of ammonia s log base dissociation constant (pKb) of approximately 9.00, at low pHs, ammonium is dominant and at pHs greater than 9.00, ammonia dominates. Ammonia is generally the form toxic to aquatic organisms while ammonimn is relatively non-toxic [34,51]. A number of methods exist to characterize anunonia caused toxicity in interstitial waters (see sections on pH manipulation and zeolite column chromatography). The two methods used most commonly in marine sediment TIEs are the addition of the macroalgae Ulva lactuca and the mineral zeoUte. 

The results of such studies are summarized in Table 3.13. The NMR studies prior to about 1970 should be viewed with cautirm, and most of the early work has been repeated with modem instrumentation and methods of analysis. For the M(OH2)5acid dissociation constant for the parent M(OH2)g ion. The AH° and AV° of often must be approximated, and this produces some uncertain in tte activation paramet for the M(OH j(OE ions. 

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