(628e) Molecular Origin of the Proton Buffering Properties of Polymeric Amines | AIChE

(628e) Molecular Origin of the Proton Buffering Properties of Polymeric Amines


Lee, H. - Presenter, Purdue University
Son, Sr., S. H. - Presenter, Purdue University
Won, Y. Y. - Presenter, Purdue University
Sharma, R. - Presenter, Purdue University

Timely escape of polymer/DNA complex particles (polyplexes) from the endosomal compartments is one of the key requirements of an efficient intracellular transport of polyplexes. In this regard, it has been believed that successful gene delivery relies, in large part, on the proton buffering capacity of the polycation molecules from which the polyplex particles are assembled. To understand the exact chemical/molecular factors that impart some polycations with the proton buffering capability, we have conducted a systematic investigation of the protonation behavior of various kinds of polycations, including the commonly studied poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and linear poly(ethyleneimine) (PEI) polycations, by using combined experimental and theoretical approaches. The results of our experiments establish the following important conclusions: (1) it is the connectivity of the amine groups in a polycation chain that causes the retardation of the protonation of the amine groups relative to the same compounds in their monomeric state (which in turn causes the proton buffering effect); (2) the proton-absorbing capacity of polycations is significantly reduced in the presence of other electrolytes in the physiological medium (such as salt ions); (3) the complexation of the polycations with polyanions (e.g., DNA) also significantly decreases the proton buffering capacity of a polycation. Ab initio DFT calculations suggest that both the solvent-mediated, screened electrostatic repulsion between adjacent charged groups and the (quantum mechanical) electron delocalization effect are responsible for the suppression of the ionization and thus the proton buffering property of polycations. The details of the results will be discussed in the presentation.