AMINO ACID NATURE OF AMPICILLIN AND RELATED PENICILLINS

The amphoteric penicillins, ampicillin and Wy‐4508 (cyclacillin), possess properties similar to the alicyclacillinphatic amino acids. At a pH equal to the isoelectric point (PI) they exist essentially as zwitterions (dipolar ions), and in this form are most stable and least soluble in water. The aqueous solubility of ampicillin changes only slightly with a change in ionic strength unless a nonpolar solvent is added. In water at 25°, the carboxyl groups of all penicillins appear to have the same pK1 (2.6‐2.7), while the amino groups of the amphoteric penicillins vary in the pK2 values over a wide range (7.24‐7.65), probably being influenced by the adjacent side chin groups. A change in the dielectric constant affects the pK1 more than the pK2; a change in temperature does the opposite. The formation of ampicillin zwitterions from its uncharged species is an exothermic reaction, and the heat of formation is about 10.7 kcal./mole. Copyright © 1969 Wiley‐Liss, Inc., A Wiley Company