Chemical equilibrium ionization constants

Another parameter that can prove helpful in identification of the chemical nature of the charged groups involved in the reaction is the enthalpy of ionization (AH°). This enthalpy of ionization is determined from the temperature dependence of the equilibrium ionization constant Ka, as described in the chemical kinetics section. The identity of amino acids present in the active site of an enzyme could be potentially identified from their characteristic pK and AH° (Table 6.1). 

The link between UpophiUcity and point charges is given by intermolecular electrostatic interactions (Sections 12.1.1.2, 12.1.3 and 12.1.4 address this topic) and ionization constants. The mathematical relationships between Upophilicity descriptors and pKjS are discussed in detail in Chapter 3 by Alex Avdeef. Here, we recall how pKj values are related to the molecular electron flow by taking the difference between the pfCj of aromatic and aUphatic amines as an example. The pfCa of a basic compound depends on the equilibrium shown in Fig. 12.2(A). A chemical effect produces the stabilization or destabiUzation of one of the two forms, the free energy difference (AG) decreases or increases and, consequently. 

The papers in the second section deal primarily with the liquid phase itself rather than with its equilibrium vapor. They cover effects of electrolytes on mixed solvents with respect to solubilities, solvation and liquid structure, distribution coefficients, chemical potentials, activity coefficients, work functions, heat capacities, heats of solution, volumes of transfer, free energies of transfer, electrical potentials, conductances, ionization constants, electrostatic theory, osmotic coefficients, acidity functions, viscosities, and related properties and behavior. 

For example, let s write the equilibrium constant expression for the basic ionization of ammonia in water. The equation for the chemical equilibrium reaction is ... 

A mixture of electrons, ions, and atoms forms a system similar to that which we considered in Chap. X, dealing with chemical equilibrium in gases. Equilibrium is determined, as it was there, by the mass action law. This law can be derived by balancing the rates of direct and inverse collisions, but it can also be derived from thermodynamics, and the equilibrium constant can be found from the heat of reaction and the chemical constants of the various particles concerned. The heats of reaction can be found from the various ionization potentials, quantities susceptible of independent measurement, and the chemical constants are determined essentially as in Chap. VIII. Thus there are no new principles involved in studying the equilibrium of atoms, electrons, and ions, and we shall merely give a qualitative discussion in this section, the statements being equivalent to mathematical results which can be established immediately from the methods of Chap. X. 

Dissociation constants, which are chemical equilibrium constants for dissolution of acids, are defined in a manner similar to the definition of pH in the case of water. As discussed before, a weak acid such as H3PO4 goes through step-by-step ionization in water given by Eqs. 4.7-4.9. In each step, the dissociation constant is experimentally found to be... 

Some ionizing solvents are of major importance in analytical chemistry whilst others are of peripheral interest. A useful subdivision is into protonic solvents such as water and the common acids, or non-protonic solvents which do not have protons available. Typical of the latter subgroup would be sulphur dioxide and bromine trifluoride. Non-protonic ionizing solvents have little application in chemical analysis and subsequent discussions will be restricted to protonic solvents. Ionizing solvents have one property in common, self-ionization, which reflects their ability to produce ionization of a solute some typical examples are given in table 3.2. Equilibrium constants for these reactions are known as self-ionization constants. 

Sections 3.3.1 and 4.2.1 dealt with Bronsted acid/base equilibria in which the solvent itself is involved in the chemical reaction as either an acid or a base. This Section describes some examples of solvent effects on proton-transfer (PT) reactions in which the solvent does not intervene directly as a reaction partner. New interest in the investigation of such acid/base equilibria in non-aqueous solvents has been generated by the pioneering work of Barrow et al. [164]. He studied the acid/base reactions between carboxylic acids and amines in tetra- and trichloromethane. A more recent compilation of Bronsted acid/base equilibrium constants, determined in up to twelve dipolar aprotic solvents, demonstrates the appreciable solvent influence on acid ionization constants [264]. For example, the p.Ka value of benzoic acid varies from 4.2 in water, 11.0 in dimethyl sulfoxide, 12.3 in A,A-dimethylformamide, up to 20.7 in acetonitrile, that is by about 16 powers of ten [264]. 

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. 

In the early stage of preformulation, characterization of the drug molecule involves ionization constants and partition coefficient determinations, aqueous and nonaqueous kinetic and equilibrium solubility determination, pH solubility profile, chemical stability assessment, and salt and polymorph screening. Assessment of biopharmaceutics and toxicological screening are also essential... 

The thermodynamics of 2D Meads overlayers on ideally polarizable foreign substrates can be relatively simply described following the interphase concept proposed by Guggenheim [3.212, 3.213] and later applied on Me UPD systems by Schmidt [3.54] as shown in Section 8.2. A phase scheme of the electrode-electrolyte interface is given in Fig. 8.1. Thermodynamically, the chemical potential of Meads is given by eq. (8.14) as a result of a formal equilibrium between Meads and its ionized form Me in the interphase (IP). The interphase equilibrium is quantitatively described by the Gibbs adsorption isotherm, eq. (8.18). In the presence of an excess of supporting electrolyte KX, i.e., c , the chemical potential is constant and... 

Acidity constants for ionization of weak carbon acids in water caimot be determined by direct measurement when the strongly basic carbanion is too unstable to exist in detectable concentrations in this acidic solvent. Substituting dimethyl-sulfoxide (DMSO) for water causes a large decrease in the solvent acidity because, in contrast with water, the aprotic cosolvent DMSO does not provide hydrogenbonding stabilization of hydroxide ion, the conjugate base of water. This allows the determination of the pfC s of a wide range of weak carbon acids in mixed DMSO/water solvents by direct measurement of the relative concentrations of the carbon acid and the carbanion at chemical equilibrium [3, 4]. The pfC s determined for weak carbon acids in this mixed solvent can be used to estimate pfC s in water. 

Acid ionization constant. The equilibrium constant for the acid ionization. (15.5) Actinide series. Elements that have incompletely filled 5/ subshells or readily give rise to cations that have incompletely filled 5/subshells. (7.9) Activated complex. The species temporarily formed by the reactant molecules as a result of the collision before they form the product. (13.4) Activation energy. The rninimum amount of energy required to initiate a chemical reaction. (13.4)... 

Another important drug physicochemical phenomenon is the ionization of Bronsted acids and bases in aqueous solution that plays a central role in much of chemistry and biochemistry and that also affects drug in vitro stability and in vivo metabolism activity. The extent of ionization can be represented by the pKg or ionization constant, which often is used in predicting drug-drug interaction because of the change of acid or base properties. For example, given a weak acid HA, its dissociation in water is subject to the chemical equilibrium ... 

In these two ionization examples, aU species in the chemical equilibrium are dissolved in water. This means that the molar concentrations needed in the equilibrium constant expression are all real numbers that can be used in the calculations. This includes the un-ionized species (e.g., HC2H3O2 and NH4OH), as well as the ions. 

An acid dissociation constant, Aa, (also known as acidity constant, or acid-ionization constant) is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction known as dissociation in the context of acid-base reactions. The equilibrium can be written symbolically as ... 

The chemical potency or inherent toxicity of a variety of organic chemicals is essentially constant, when expressed in terms of the organism toxicant concentration, for the nature of the biological response and the type of toxic action discussed herein. Specifically, the product of molar water toxicant concentration times bioconcentration factor is a constant when steady-state equilibrium is approached, and ionization, if it occurs, is taken into account. 

Nevertheless, chemical methods have not been used for determining ionization equilibrium constants. The analytical reaction would have to be almost instantaneous and the formation of the ions relatively slow. Also the analytical reagent must not react directly with the unionized molecule. In contrast to their disuse in studies of ionic equilibrium, fast chemical reactions of the ion have been used extensively in measuring the rate of ionization, especially in circumstances where unavoidable irreversible reactions make it impossible to study the equilibrium. The only requirement for the use of chemical methods in ionization kinetics is that the overall rate be independent of the concentration of the added reagent, i.e., that simple ionization be the slow and rate-determining step. 

Like all chemical equations, this one has an equilibrium constant. The discussion of basic chemistry is outside the purview of this book. Readers who may need a refresher are referred to Tse and Jaffe (1991). For every chemical, a pKa can be calculated, based on its equilibrium constant, which represents the proportion of ionized and unionized material in solution. The lower the pKa of a chemical, the more likely it is to be nonionized in the stomach. 

Proton transfer is one of the prominent representatives of an ion-molecule reaction in the gas phase. It is employed for the determination of GBs and PAs (Chap. 2.11.2) by either method the kinetic method makes use of the dissociation of proton-bound heterodimers, and the thermokinetic method determines the equilibrium constant of the acid-base reaction of gaseous ions. In general, proton transfer plays a crucial role in the formation of protonated molecules, e.g., in positive-ion chemical ionization mass spectrometry (Chap. 7). 

Equations (1.206) and (1.207) describe the ionization of neutral vacancies (Vx, Vm). We assume here that the ionization of V and Vm to Vx and Vm does not take place. In a crystal in thermal equilibrium, electrons and holes will be formed by thermal excitation of electrons from the valence band to the conduction band, and the reverse process is also possible. This process can be expressed by eqn (1.210) as a chemical reaction, (see eqn (1.136)). Such reactions are called creation-annihilation reactions. Equations (1.208) and (1.209) describe the creation-annihilation reactions of neutral vacancies and charged vacancies in a crystal. Equation (1.211) shows the formation reaction of MX from constituent gases. It is to be noted that of these eight equations two are not independent. For example, the equilibrium constants Ks and K x in eqns (1.209) and (1.211) are expressed in terms of the other Ks as... 

This chapter begins with descriptions of the physical and chemical properties of water, to which ail aspects of cell structure and function are adapted. The attractive forces between water molecules and the slight tendency of water to ionize are of crucial importance to the structure and function of biomolecules. We review the topic of ionization in terms of equilibrium constants, pH,... 

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