Ionization of weak acids and bases

As will be seen, the large amount of quantitative structure-activity relationship (QSAR) modeling that has been carried out for soil sorption has almost exclusively involved nonionic organic compounds. For strongly ionizing and inorganic chemicals, no QSARs are available. However, Bintein and Devillers (1994) developed a soil sorption QSAR that incorporated correction factors for ionization of weak acids and bases. 

Calculations regarding the influence of pH upon the ionization of weak acids and bases may be solved by applying the Henderson-Hasselbalch equation (pH - pKz = log[base/acid]), which may be familiar to you from taking a class in biochemistry. 

This equation essentially describes the relationship between pH and the degree of ionization of weak acids and bases. When applied to drugs, the equation tells us that when pH equals the apparent equilibrium dissociation constant of the drug (pKJ, 50 percent of the drug will be in the unionized form and 50 percent will be in the ionized form (i.e., log[base/acid] = 0 and antilog of 0 = 1, or unity). Application of the Henderson-Hasselbalch equation can, therefore, allow one to mathematically determine the exact proportion of ionized and nonionized species of a drug in a particular body compartment if the pKa of the drug and the pH of the local environment are known. 

Strong acids and bases ionize completely in solution, while weak acids and bases partially ionize. The partial ionization of weak acids and bases creates solutions in which an equilibrium is established. 

Textbooks of analytical chemistry should be consulted for further details concerning the ionization of weak acids and bases and the theory of indicators, buffer solutions, and acid-alkali titrations. 

Note that for a reaction which produces protonated water, HjO, the constant is denoted as K, whereas for a process which produces deprotonated water, OH , the constant is denoted as K. Furthermore, the reader should understand that [H ] and [HjO ] are equivalent to each other. The simpler [H ] will be used henceforth for two reasons (1) It will simplify mathematical expressions, and (2) one ought not emphasize the difference between the hydration of all ionic substances, e.g., Na", Mg, and the hydration of the proton. The values of K s and K s indicate the extents of ionization of weak acids and bases. The larger the constants, the stronger the acids or bases. 

TTie ionization of weak acids and bases depends on the pH of the tubular Iluid. Manipulation of the urine pH is sometimes useful in increasing renal excretion. For example, bicarbonate administration makes the urine alkaline this ionizes a-spirin. making it less lipid soluble and increasing its rate of excretion. 

The Ionization of Weak Acids and Bases Is Suppressed by the Addition of a Common Ion 612... 

Notice that neutrality, that is, xa — xb = 0, occurs at pH 7 only if [A ]/Ka — [B ]/Kb- This is why a solution of sodium acetate, for example, a neutral salt of a strong base (large Kp) and a weak acid (small Ka), exhibits a high pH. The slope of a pH curve is influenced strongly by the ionization constants of both acid and base. The ionization of weak acids and bases is severely limited by the concentration of their companion ions a solution whose pH is thus limited is said to be buffered. ... 

The equivalent conductance of salts increases on dilution to a limiting value (Ao) called the limiting equivalent conductance (formerly written A, the conductance at infinite dilution ). This value can be tound experimentally and accurateh, but only for salts because the small concentration of hydrogen R)ns. maintained b the ionization of water, interferes with the ionization of weak acids and bases. For these,, o is obtained b summing the ionic conductances (ionic mobilities) of the individual ions, taken from tables such as those of... 

Equilibrium constants can be written for the ionization of weak acids and weak bases, just as for any other equilibria. For the equation... 

Sarmini, K., and Kenndler, E. (1999). Ionization constants of weak acids and bases in organic solvents. /. Biochem. Biophys. Methods 38, 123—137. 

As we explain in Chapter 16, the and are equilibrium constants that measure the tendency of weak acids and bases, respectively, to undergo ionization reactions in water. For the dissociation reaction of a weak acid, HA... 

State-of-the-art calorimetry allows the accurate determination of enthalpies and free energies of ionization with micromolar amounts of weak acids and bases. The acidic pKs as well as the neutralization enthalpies of imidazole and pyrazole have been determined by calorimetry. 

IONIZATION OF WEAK ACIDS AND WEAK BASES THE HENDERSON-HASSELBALCH EQUATION... 

Hydrochloric, sulfuric, and nitric acids, commonly called strong acids, are completely ionized in dilute aqueous solutions the strong bases NaOH and KOH are also completely ionized. Of more interest to biochemists is the behavior of weak acids and bases—those not completely ionized when dissolved in water. These are common in biological systems and play important roles in metabolism and its regulation. The behavior of aqueous solutions of weak acids and bases is best understood if we first define some terms. 

Ionization of Weak Acids and Weak Bases the Henderson-Hasselbalch Equation... 

Rejection of weak acids and bases is highly pH dependent. When the acid or base is in the ionized form the rejection will be high, but in the nonionized form rejection will be low [46,47]. Data for a few weak acids are shown in Figure 5.16. At pHs above the acid pKa, the solute rejection rises significantly, but at pHs below the pKa, when the acid is in the neutral form, the rejection falls. 

So, let s proceed with a review of the basics. We ll start with another look at equilibrium, and then the structure and nomenclature of some common acids and bases. We ll next take a look at some basic pH calculations. Then, however, we ll delve into an area that you might not have seen before ionization equilibria of weak acids and bases. Finally, we ll explore the preparation and properties of buffers. 

Calculating the pH of weak acids and bases is more challenging, because they do not ionize completely. So, in a 0.10 M solution of acetic acid, the [H+] concentration is not 0.10 M. We must use the equilibrium constant expression to find the pH of weak acid solutions. So, what is the pH of a 0.10 M solution of acetic acid The K of acetic acid is 1.8 x 10"5. 

In equations showing the reactions of weak acids and bases, the un-ionized parts cannot be neglected. Both the un-ionized and ionized parts must be shown, e.g. ... 

Thermodynamics is a branch of physical chemistry that deals quantitatively with the inter-exchange of heat and work evolved in physical and chemical processes. This subject is widely utilized to explain equilibrium systems in physical pharmacy. For example, a pharmaceutical scientist may use equilibrium thermodynamics to study isotonic solutions, solubility of drugs, distributions of drugs in different phases, or ionization of weak acids and weak bases. Even though the gas laws are not usually directly related to pharmaceutical science (with some exceptions such as aerosols), these concepts must be introduced when dealing with simple thermodynamic systems of gases and the universal gas constant, R. 

In the case of ionized compounds (weak acids and bases), drug permeation depends on the chemical equilibrium between the ionized and the un-ionized form, both in the delivery system itself and in the lacrimal fluid. In general, un-ionized molecules penetrate lipid membranes more readily than ionized ones. 

Normal salts acid salts basic salts. Hydrogen-ion concentration. / H. Indicators. Ionization equilibria of weak acids and bases. Acid constant basic constant. Titration of weak acids and bases. Choice of suitable indicator. 

Medium Effect and Ionization Constants of Weak Acids and Bases... 

The foregoing example illustrates how equilibrium constants for overall cell reactions can be determined electrochemically. Although the example dealt with redox equilibrium, related procedures can be used to measure the solubility product constants of sparingly soluble ionic compounds or the ionization constants of weak acids and bases. Suppose that the solubility product constant of AgCl is to be determined by means of an electrochemical cell. One half-cell contains solid AgCl and Ag metal in equilibrium with a known concentration of CP (aq) (established with 0.00100 M NaCl, for example) so that an unknown but definite concentration of Kg aq) is present. A silver electrode is used so that the half-cell reaction involved is either the reduction of Ag (aq) or the oxidation of Ag. This is, in effect, an Ag" Ag half-cell whose potential is to be determined. The second half-cell can be any whose potential is accurately known, and its choice is a matter of convenience. In the following example, the second half-cell is a standard H30" H2 half-cell. 

Effect of pH for lonizable Organic Solutes The distribution of weak acids and bases between organic and aqueous phases is dramatically affected by the pH of the aqueous phase relative to the plQ of the solute. As discussed earher, the pK is the pH at which 50 percent of the solute is in the ionized state. (See Dissociative Extraction in Commercial Extraction Schemes. ) For a weak organic acid (RCOOH) that dissociates into RCOO and H , the overall partition ratio for extraction into an organic phase depends upon the extent of dissociation such that... 

Since passive diffusion is the primary driving force behind dermal absorption, physicochemical factors such as molecular weight and structure, lipophilicity, pKa, ionization, solubility, partition coefficients, and diffusivity can influence the dermal absorption of various classes of chemicals. In addition penetration of acidic and basic compounds will be influenced by the skin surface, which is weakly acidic (pH 4.2-5.6), since only the uncharged moiety of weak acids and bases is capable of diffusing though the lipid pathway. Several of these factors (e.g., molecular weight, and partition coefficients) have been used to predict absorption of various drug classes [24-26],... 

The partition coefficient refers to the intrinsic lipophilicity of the drug, in the context of the equilibrium of unionized drug between the aqueous and organic phases. If the drug has more than one ionization center, the distribution of species present will depend on the pH. The concentration of the ionized drug in the aqueous phase will therefore have an effect on the overall observed partition coefficient. This leads to the definition of the distribution coefficient (log D) of a compound, which takes into account the dissociation of weak acids and bases. 

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