Ionization of weak base

The proportion of ionized and unionized forms of a chemical compound can be readily calculated according to the above equation. It can be easily seen that pK is also a pH value at which 50% of the compound exists in ionized form. The ionization of weak acids increases as the pH increases, whereas the ionization of weak bases increases when the pH decreases. As the proportion of an ionized chemical increases, the diffusion of the chemical through the biological membranes is greatly impaired, and this attenuates toxicokinetic processes. For example, the common drug acetosalicylic acid (aspirin), a weak acid, is readily absorbed from the stomach because most of its dose is in an unionized form at the acidic pH of the stomach. 

Proceeding further by using the arguments given in the two previous cases and also taking into account the three equilibria in the solution (involvement of ionization of weak base BOH weak acid HA and H20) the following relationships for Kh and h can be derived ... 

Kb is an equilibrium constant governing the ionization of weak bases. 

Acidification of urine —increases ionization of weak bases —> increases renal elimination. Alkalinization of urine — increases ionization of weak acids —> increases renal elimination. 

The ionization of weak bases is treated in the same way as the ionization of weak acids. When ammonia dissolves in water, it undergoes the reaction... 

Acidification of urine —> increases ionization of weak bases —> increases renal elimination. 

In view of the problems we have just seen which may arise in the determination of the heats of ionization of weak bases by the van t Hoff method, it is natural to consider whether these values might not be determined calorimetrically. Obviously, this cannot be done directly in dilute aqueous acid (the standard state) because weak bases are by definition not ionized in this medium. Unfortunately, there is no way that we know of to use free energy-enthalpy extrapolations across a range of aqueous acid solutions to estimate... 

The facts given above and the close parallel between 7/s values and the three acidity functions—%H2S04, IIQ and (H0 + log [H+]) suggest that linear relationships may be found which would permit the estimation of otherwise inaccessible H0 values or AHS values. This was indeed done in order to estimate the H0 acidity of fluorosulfuric acid (Fig. 3) and HSO3F—SbF5 with independent corroboration of the former value within 1 3 H0 unit (Arnett et al., 1972b). Unfortunately, we have not been able to find any objective treatment of such data which would yield reliable thermodynamic properties for ionization of weak bases in water as a standard state. 

The state of ionization of weak bases also can be described by acidic ionization constants. For example, ammonia is a weak base which can take up hydrogen ions to form ammonium ions. This is, of course, equivalent to thinking of the ammonium ion (NH4 ) as a weak acid which ionizes in water to give some hydrogen ions (H" ") and some molecules of ammonia (NH3). Thus ... 

Pyrroles do not react with alkyl halides in a simple fashion polyalkylated products are obtained from reaction with methyl iodide at elevated temperatures and also from the more reactive allyl and benzyl halides under milder conditions in the presence of weak bases. Alkylation of pyrrole Grignard reagents gives mainly 2-alkylated pyrroles whereas N-alkylated pyrroles are obtained by alkylation of pyrrole alkali-metal salts in ionizing solvents. 

Textbooks of analytieal ehemistry should be eonsulted for further details eoneeming the ionization of weak aeids and bases and the theory of indieators, buffer solutions, and aeid-alkali titrations. " ... 

Equilibrium constants of weak bases can be measured in the laboratory by procedures very much like those used for weak acids. In practice, though, it is simpler to take advantage of a simple mathematical relationship between Kb for a weak base and Ka for its conjugate acid. This relationship can be derived by adding together the equations for the ionization of the weak acid HB and the reaction of the weak base B- with water ... 

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

It was soon realized that there are problems with this approach.24,25 Log ionization ratios for weak bases that are not primary aromatic amines, while linear in H0, do not give the unit slope required by equation (8). This soon led to many other acidity functions, defined for other types of weak base, HA for amides,24 Hq for tertiary aromatic amines,25 C0 or HR for carbocations,26,27 and so on. In a recent review of addity functions,28 28 different ones were listed... 

Buffers contain mixtures of weak acids and their salts (i.e., the conjugate bases of acids), or mixtures of weak bases and their conjugate acids. Typical buffer systems used in pharmaceutical dosage forms include mixtures of boric acid and sodium borate, acetic acid and sodium acetate, and sodium acid phosphate and disodium phosphate. The reason for the buffering action of a weak acid, HA (e.g., acetic acid) and its ionized salt, A" (e.g., sodium acetate) is that A" ions from the salt combine with the added hydrogen ions, removing them from solution as undissociated weak acid. 

Reverse-phase chromatography is used mainly for the separation of nonionic substances because ionic, and hence strongly polar, compounds show very little affinity for the non-polar stationary phase. However, ionization of weak acids (or weak bases) may be suppressed in solvents with low (or high) pH values. The effect of such a reduction in the ionization is to make the compound more soluble in the non-polar stationary phase but the pH of the solvent must not exceed the permitted range for bonded phases, i.e. pH 2-8. 

Excretion of drugs will be affected by the pH of the urine. If the urine is acidic, weak bases are ionized and there will be poor re-absorption. With basic urine, weak bases are non-ionized and there is more re-absorption. The pH of the urine can be artificially changed in the range 5-8.5 oral administration of sodium bicarbonate (NaHCOs) increases pH values, whereas ammonium chloride (NH4CI) lowers them. Thus, urinary acidification will accelerate the excretion of weak bases and retard the excretion of weak acids. Making the urine alkaline will facilitate the excretion of weak acids and retard that of weak bases. 

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

Depending on these conditions, various NMR methods have been proposed and used to calculate the ionization ratio of weak bases in a superacid medium. 

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

Weak acids and weak bases, for which ionization can be suppressed, may be separated on reversed-phase columns by the technique known as ion suppression. In this technique a buffer of appropriate pH is added to the mobile phase to render the analyte neutral or only partially charged. Acidic buffers such as acetic acid are used for the separation of weak acids, and alkaline buffers are used for the separation of weak bases.25 As a result of the added buffer, samples are eluted as sharper zones than they would have been in a similar mobile phase without the addition of a modifier.24... 

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