Understanding the pH-Directed Self-Assembly of a Four-Arm Block Copolymer

We
investigated the pH-directed self-assembly of Tetronic 304 (T304),
an amphiphilic four-arm block copolymer of interest for application
in drug delivery systems. While T304 and its analogues have been investigated
regarding their pharmaceutical and therapeutic applications, a fundamental
understanding of their pH-directed self-assembly is lacking. Integrating
unbiased molecular dynamics simulations with small-angle neutron scattering
and dynamic light scattering experiments provided an unprecedentedly
detailed interpretation of our experimental findings and also directed
the selection of suitable models for experimental data analysis. We
subsequently probed the interactions that drive and hinder the self-assembly
of T304 at the atomistic level of detail. pH-driven conformation changes
in the central ethylenediamine group of T304, and subsequent interactions
with water, ultimately drive the self-assembly of T304 and the structure
of the resulting polymeric micelles. Our work provides detailed mechanistic
understanding of pH-directed polymer self-assembly and supports the
rational design of new pH-responsive functional polymer materials.