Acid-base ionization properties

Knowledge of acid-base ionization properties is essential to an understanding of solubility properties, partitioning, complexation, chemical stability, and drug absorption. The ionized molecule exhibits markedly different properties from the corresponding un-ionized form. 

ADMET Predictor Constitutional, functional group counts, topological, E-state, Moriguchi descriptors, Meylan flags, molecular patterns, electronic properties, 3D descriptors, hydrogen bonding, acid-base ionization, empirical estimates of quantum descriptors 297... 

The charge properties of amino acids are very important in determining the reactivity of certain amino acid side chains and in the properties they confer on proteins. The charge properties of amino acids in aqueous solution may best be considered under the general treatment of acid-base ionization theory. We find this treatment useful at other points in the text as well. 

Just like activated carbons and hydrous oxides, potentiometric titration can be used to characterize the acid-base surface properties of the resins (4—8,12,15-19). The ionization reactions and the constants (pK values) can be determined according to the titration data. For example, Chen and co-workers reported a successful case of characterization of a cation resin—a calcium alginate based ion exchange resin (CABIER) (17). The study included three steps ... 

Our discussion of acid-base ionization and salt hydrolysis in Chapter 15 was limited to solutions containing a single solute, hi this section we will consider the acid-base properties of a solution with two dissolved solutes that contain the same ion (cation or anion), called the common ion. 

It is very instructive to compare the kinetics and plausible mechanisms of reactions catalyzed by the same or related catalyst(s) in aqueous and non-aqueous systems. A catalyst which is sufficiently soluble both in aqueous and in organic solvents (a rather rare situation) can be used in both environments without chemical modifications which could alter its catalytic properties. Even then there may be important differences in the rate and selectivity of a catalytic reaction on going from an organic to an aqueous phase. TTie most important characteristics of water in this context are the following polarity, capability of hydrogen bonding, and self-ionization (amphoteric acid-base nature). 

One has to emphasize that MS also is associated with several drawbacks when it comes to bioactivity screening. First of all, the optimum, native conditions for bioactivity screening (pH 7.2, addition of 150 mM sodium chloride) are entirely incompatible with optimum conditions for MS detection which, for ESI-MS, typically require acidic pH values and the presence of organic modifiers to enhance ionization properties of the analytes. Assay development for MS-based assays therefore mainly requires the testing of different assay conditions, particularly the replacement of nonvolatile buffers with MS-compatible volatile buffers. Furthermore, it is essential to monitor ion suppression effects, for example, by the... 

We have so far considered acids and bases with a single ionizable group, and have rationalized the measured values in relation to structural features in the molecule. This additional structural feature could well have its own acidic or basic properties, and we thus expect that such a compound will be characterized by more than one pK value. 

As emphasized earlier, the concentration gradient of the drug in Eq. (1) refers to that of the unbound drug and its ionic distribution, which depends upon its acid-base properties. This can be modified by appropriate choice of excipients to ionize the drug by salt formation, thereby affecting the distribution of ionic versus nonionic species by acid-base equilibrium, using the Henderson-Hasselbach equation. All of the drug will eventually leave the depot and enter the body, but the rate may be reduced if membrane transport is limited by solubility of the neutral species within the membrane. 

Amino acids vary in their acid-base properties and have characteristic titration curves. Monoamino monocarboxylic amino acids (with nonionizable R groups) are diprotic acids (+H3NCH(R)COOH) at low pH and exist in several different ionic forms as the pH is increased. Amino acids with ionizable R groups have additional ionic species, depending on the pH of the medium and the pIQ of the R group. 

The acid-base properties, and hence ionic character, of peptides and proteins also can be used to achieve separations. Ion-exchange chromatography, similar to that described for amino acids (Section 25-4C), is an important separation method. Another method based on acid-base character and molecular size depends on differential rates of migration of the ionized forms of a protein in an electric field (electrophoresis). Proteins, like amino acids, have isoelectric points, which are the pH values at which the molecules have no net charge. At all other pH values there will be some degree of net ionic charge. Because different proteins have different ionic properties, they frequently can be separated by electrophoresis in buffered solutions. Another method, which is used for the separation and purification of enzymes, is affinity chromatography, which was described briefly in Section 9-2B. 

The surface potential (j)s depends on the concentration profiles of all ionic species present at the interphase, including ionic strength affecting the diffuse layer, specifically adsorbed ions, and surface ionizable groups. Thus, the surface itself possesses acid-base properties that are reflected in the response of the immobilized indicator dye but are not uniquely linked to the pH of the bulk of the solution. 

So, the pH of pure water is 7.00 because that is the negative logarithm of the hydrogen ion concentration that is generated by the self ionization of water. It is a value based on the inherent acid-base properties of water. 

The physical properties of the phenols listed in Figure 14.3 are summarized briefly in Table 14.2. These phenolic compounds are weak acids that ionize to phenolate ions in the presence of base ... 

In petroleum oils, no ionization of acids, bases or salts takes place. Thus, the pH concept cannot be used directly (Frewing, 1962) however, the properties of base and acid mixtures in low-polar media have been studied extensively (Pawlak et al.,1989). Information from these studies has been used to overcome the difficulties inherent in analyzing petroleum products. 

Separation of proteins based on differences in their electrical charge depends on their acid-base properties, which are mostly determined by the number and type of ionizable side groups in the peptide chain. Since proteins are different from each other with respect to their composition and amino acid sequence, they also have distinct acid-base properties. Information on these properties allows a prediction of the behavior of a given protein when exposed to an electrical field. 

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