The ionization constant Ka

The earliest successful parameterization of electrical effects is due to Hammett . Though Burkhardt reported the existence of QSRR two years before Hammett, he did not develop a general relationship. Hammett defined the and Op constants using the ionization constants Ka,x of 3- and 4-substituted benzoic acids in water at 25 °C as the reference set and hydrogen as the reference substituent Kh) to which all others are compared. For hydrogen, the values of the and Op constants were defined as zero (equation 3) ... 

It is usual to discuss the ionization of a base B in terms of its conjugate acid BH+ in order to use the same set of equations for both acids and bases. The ionization constant Ka is defined by... 

Suppose that one of the kinetic quantities, such as fccat, depends on the enzyme being in the acidic form. Then the rate will depend upon the ionization constant Ka and the pH according to... 

Antimicrobial activity, within a pharmaceutical context, is generally found only in the organic acids. These are weak acids and will therefore dissociate incompletely to give the three entities HA, H+ and A- in solution. As the undissociated form, HA, is the active antimicrobial agent, the ionization constant, Ka, is important and the pKa of the acid must be considered, especially in formulation of the agent. 

As the number of carbon atoms increases in an acid, ionization decreases, and hence the ionization constant (Ka) decreases. Because of the decrease in the concentration of hydrogen ions, acidic strength decreases as shown in Table 3. 

Generally, drug substances capable of undergoing ionization yield more complex pH-rate profiles. For example, each ionic and nonionic form of the drug could be subject to hydronium ion, hydroxide ion, and water catalysis. When this happens, the expression for , s may contain more than three terms. For example, apparent degradation rate constants for a drug substance that is a weak base will depend on the ionization constant, Ka of the conjugate acid of the weak base and the concentration of hydronium ion and other species, as described by... 

Lactic acid, HC3H5O3, is found in sour milk, where it is produced by the action of lactobacilli on lactose, or milk sugar. A 0.025 M solution of lactic acid has a pH of 2.75. What is the ionization constant Ka for this acid What is the degree of ionization ... 

Weak Acids and Weak Bases—A weak acid or weak base ionizes to a limited extent in water. The extent of their ionization can be related to the ionization constants Ka and Kt, or their logarithmic equivalents pKa = -log Ka and pKt, = -log Kt, (Table 16.4) by setting up and solving an equilibrium calculation. Calculations involving ionization equilibria are in many ways similar to those introduced in Chapter 15, although some additional considerations are necessary for polyprotic acids. 

Replacement of a hydrogen atom by an alkyl group such as a methyl group Usually has no effect, or only a very small effect, on the ionization constant thus, the ionization constant of HXMe+ is approximately equal to Ku and that of MeXH to Ka. Therefore,... 

It follows that Kt can be theoretically calculated from Kt and the ionization constant of either of the alkylated derivatives. In practice, however, this can only be done if there is an appreciable difference between the constant for the alkylated derivative and the value of Kt. Mason has argued that it is better to use the ionization constants of both alkylated forms in the equation Kt = Xmethyl groups can be base-weakening as well as base-strengthening the data shown in Table I indicate that the base-weakening inductive... 

LFER. Consider the rate of base hydrolysis of a series of ethyl benzoates given by d[C2HsOH]/dt = LfdALQ COOQHsHOH"]. Show that a plot of log Jfcx versus log Ka, where Ka is the ionization constant of the parent benzoic acid, should be linear, and relate its slope to that given by a conventional Hammett plot of log k versus a. 

The Hammett equation is the best-known and most widely studied of the various linear free energy relations for correlating reaction rate and equilibrium constant data. It was first proposed to correlate the rate constants and equilibrium constants for the side chain reactions of para and meta substituted benzene derivatives. Hammett (37-39) noted that for a large number of reactions of these compounds plots of log k (or log K) for one reaction versus log k (or log K) for a second reaction of the corresponding member of a series of such derivatives was reasonably linear. Figure 7.5 is a plot of this type involving the ionization constants for phenylacetic acid derivatives and for benzoic acid derivatives. The point labeled p-Cl has for its ordinate log Ka for p-chlorophenylacetic acid and for its abscissa log Ka for p-chloroben-zoic acid. The points approximate a straight line, which can be expressed as... 

C). The value of a may be determined from its definition in terms of the ionization constant if the appropriate benzoic acid derivative has been measured. Such a values may then be used to determine p values for other reactions, and these p values in turn lead to the possibility of determining new o values. Equation 7.4.24 implies that a plot of log KA or log kA versus oA should be linear for a given series of reactions involving the same reactive groups. Extensive experimental evidence attests to this relation. Table 7.2 contains some values that have been reported in the literature. Extensive tabulations... 

The rate coefficient (k2 enc) for the collision of two species is given by 8RT/3Z (where Z is the viscosity of the medium at the reaction temperature), the Smoluchowski equation. This is the maximum possible rate of reaction, which is controlled by the rate at which the two reacting species diffuse together. For nitration in >90% H2S04, where nitric acid is completely ionized, if exclusively the free base nitrates the rate coefficient (k2 fb) would equal k2 obs KJhx (where Ka is the ionization constant of the base, and hx the acidity function that it follows). Thus, if k2 fb> k2 enc free base nitration is precluded, but if... 

Solvents. Reagent grade THF (nD25 = 0.888, bp = 64-66°C) containing 0.025 wt-vol % di-ferf-butyl-p-cresol which served as an antioxidant was used for the preparative GPC fractionation. The solvent TFE (nD20 = 1.2907, d25 = 1.3823, bp = 76°C, ionization constant Ka — 4.3 X 10"13) was obtained from Halocarbon Products Corp., Hackensack, N. J., and was used for both analytical GPC and viscometry. The recovery and... 

The value of Kapp is pH dependent. It is seen in Chapter 5 (equation 5.8) that equation 3.80 is the equation for the ionization of an acid of ionization constant Ka. At high pH where [H+] < KA or K A, appOrighpH) = K. At low pH where [H+] Ka oiKa, A appdowpH) = KKa/K a. Applying the rules for cyclic equilibria above, rapp(highpH) = % The values of Km at extremes of pH should be obvious from examination of scheme 3. 

The effect of various surfactants, the cationics-eetyl trimethyl ammonium bromide (CTAB), and cetyl pyridinium chloride (CPC), the anionic-sodium lauryl sulfate (SLS), and the nonionic-polysorbate 80 (Tween 80), on the solubility and ionization constants of some sparingly soluble weak acids of pharmaceutical interest was studied (Gerakis et al., 1993). Benzoic acid (and its 3-methyl-, 3-nitro-, and 4-tert-butyl-derivatives), acetylsalicylic acid, naproxen, and iopanoic acid were chosen as model drugs. The cationics, CTAB and CPC, were found to considerably increase th< ionization constant of the weak acidS Ka ranged from-0.21 to-3.57), while the anionic, SLS, showed a negligible effect and the nonionic, Tween 80, generally decreased the ionization constants Solubility of the acids increased in aqueous micellar and in acidiLed micellar solutions. 

The compound can only be a carboxylic acid no other class containing only carbon, hydrogen, and oxygen is more acidic. A reasonable choice is HC=CCOzH C-2 is sp-hybridized and therefore rather electron-withdrawing and acid-strengthening. This is borne out by its measured ionization constant Ka, which is 1.4 X 10 2 (pATa 1.8). 

All other acids (that we ll mention) are weak acids. The vast majority of acids fall into this category. However, weak acids show a range of acid strength. The relative strength of a weak acid is quantified by the equilibrium constant Ka governing the ionization of the weak acid. 

Further, the polymerization constant ks (referring to the formation of a siloxane bond) and the ionization constant Ki are assumed not to be modified by the presence of aluminum atoms. The ka value, corresponding to the formation of a Si-O-Al bond, aas estimated by iteration according to values originating from a semi-quantitative experimental study (29) and aas found to be 35. The follo-aing results are based upon an example from this study. 

Hence, assuming that the equilibrium constant Ka is the same for the ionization of HA inside and outside the mitochondrion, and the value of Ka is sufficiently low that [HA]=0 and it will not contribute to the measurements, then... 

The higher the ionization constant, the stronger the acid, and consequently the weaker the base. Thus the value of Ka is at the same time a measure of the strength of the base there is no need to define a base ionization constant separately. 

If we take a series of compounds which are related by structural substitutions, such as benzene derivatives, then we can assign the effects of the structural changes to the ratio KBJKB. if we select this property as a standard. Such a system of correlation was first proposed by Hammett and revised and extended by Jaff " to account for the effects of meta and para substituents on the reactivity of benzene derivatives. For convenience, the ionization constant of benzoic acia queous solution at 25°C was chosen as standard and for each meta or para substituent a, a value of ionization constant for benzoic acid and Ka the ionization constant of the corresponding, substituted benzoic acid. 

Slant of the mobile phases decreases. The dielectric constant is expected to influence the position of the equilibrium in ionic secondary chemical equilibria of acidic compounds [80-83], The solvent has the ability to disperse electrostatic charges via ion-dipole interactions, which is inversely proportional to the dielectric constant of the solvent composition. The lower the dielectric constant, the lower the ionization constant of the acid, Ka, and consequently greater Ka values are obtained. 

The experimental techniques used to obtain the properties necessary to derive the kinetic constants of interest from the ultrasonic relaxation times have been previously described in detail [2,3]. Briefly, the degree of micelle ionization (P) and the binding constant (Ka) of an alcohol to mixed micelles were obtained from specific conductivity measurements as a function of surfactant concentration at various fixed alcohol compositions. The binding constant was determined from the slopes of the curves above the cmc, as proposed by Abu-Hamdiyyah et al... 

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