Amino acids, basicity ionization constants

The effect of changing pH is different in the two examples given. With alanylglycine the degree of synthesis increases progressively on either side of pH 6, whereas with benzoyltyrosylglycineamide it decreases. The reason is that in the first case the product is a zwitterion whose acid ionization constant is less, and whose basic ionization constant is about twenty-five times stronger, than that of either of its constituent amino acids. 

None of the other reactions so far discussed involve interaction between a pair of charged species. This is but another instance of the electrostatic effect shown by Kirkwood and Westheimer to be responsible for the disparity between the first and second ionization constants of dibasic acids, for the effect of the carboxylate ion on the basicity of an a-amino acid, and for the difference in reactivity of ionic compounds compared with analogous nonionic species in acid- or base-catalyzed reactions. ... 

Hydrogen ion titration curves of proteins provide a powerful tool to reveal many aspects of the structures of individual proteins. The characteristic ionization constants of the acidic and basic groups in the amino acids and peptides may be profoundly modified when these groups are incorporated in a protein molecule. An increasing number of proteins have been found in which potentially reactive groups are inaccessible for titration in the native molecule, and become available only after denaturation. Such findings can, in the years ahead, be correlated with detailed knowledge of the three dimensional structure of proteins, as obtained by X-ray diffraction and other methods. The present state of the field is reviewed by Tanford, who has done so much to advance it over the last decade. 

In order to illustrate the hybrid ion theory, we shall compare ammonium acetate with an amino acid of which the acid and basic dissociation constants are respectively the same as those of acetic acid and ammonium hydroxide. We know that in 0.1 molar solution, ammonium acetate is 0.5% hydrolyzed and the salt is 99.5% ionized. If we employ the same equation (40 in Chapter One) to calculate the degree of hydrolysis of the amino acid, we find that it too is 0.5% hydrolyzed. Thus it appears logical to assume that the remainder of the ampholyte is present in the ionogenic form. 

The reaction medium, especially the pH, determines the constants for a given pair of reactants. To obtain an equilibrium that is shifted in favor of peptide product formation the ionization equilibrium must be manipulated. One efficient method is the addition of water-miscible organic solvents to the aqueous reaction mixture thereby lowering the dielectric constant of the medium, reducing the acidity of the carboxyl group, and to a lesser extent the basicity of the amino group of the nucleophilic amine component[100 1011 The use of biphasic systems (for a review... 

---