Potentiometric Determination of Acid Dissociation Constants (p ) for an Anticancer Pyrrole-Imidazole Polyamide.

To optimize the pharmacological properties of an anticancer pyrrole-imidazole (Py-Im) polyamide (), we characterized the acid dissociation constants of , three other structurally related hairpin-shaped polyamides, and a cyclic polyamide bearing the same core sequence as via potentiometric titration. The acidities of the carboxylic acid at the C-terminus and the tertiary amine in the triamine linker remained very similar among the polyamides tested, whereas the p of the -methylimidazole (Im) moieties varied with the peptide sequence and molecular architecture. A nearly 0.