Determination of the intrinsic proton binding constants for poly(amidoamine) dendrimers via potentiometric pH titration

Protonation of fourth-generation poly(amidoamine) dendrimers terminated with hydroxyl and amine functional groups has been studied by potentiometric pH titration. The titration data are analyzed using a multishell structural model and a Frumkin adsorption isotherm to approximate proton-dendrimer binding equilibria. Site-to-site correlation is ignored, and counterions are treated according to the standard Debye-Huckel theory. This analysis yields two binding parameters: the intrinsic proton binding constant and a constant that characterizes the strength of electrostatic interactions among occupied binding sites. For the hydroxyl-terminated dendrimers, the internal tertiary amines have an average binding constant (pK = 6.30) 1-2 pH units lower than the value expected for a single, isolated binding site. This shift in pK is attributed to a hydrophobic microenvironment within the dendrimer interior. In contrast, no significant shift has been observed in the binding constant (pK = 9.23) for the peripheral primary amines in the amine-terminated dendrimer because the microenvironment around the primary amines is more hydrophilic. The strength of electrostatic interactions obtained from titration data is 3 times (primary amines) and 8 times (tertiary amines) smaller than the calculated values based on the multishell model. We hypothesize that the diminished interaction strength results from ion pairing between bound protons and counterions. In addition to the Debye-Huckel contribution from mobile ions, ion pairing provides extra Coulomb charge screening.