The cooperative ionization transitions of hydrophobic polyelectrolytes
Authors:   , Martín Robinson James Luis 
Published: October 2024

This thesis is dedicated to the pH-driven ionization transitions of hydrophobic polyelectrolytes (HPEs). This class of weak polyelectrolyte contains significant hydrophobic character and exhibits distinct behaviour to that of other polyelectrolytes. For certain systems, these ionization transitions such as micellization, oil-water partitioning and membrane solubilization can be remarkably sharp. The aim of this work is to understand the underlying mechanisms leading to this behaviour, and be able to reliably design systems that exhibit it. We attempt to unify distinct phenomena under the same framework via a combination of theory and experiment.
Being able to predict at which pH these polymers will undergo a transition, and with what degree of sharpness, will be essential with respect to their use in practical applications.
The central theoretical ideas in this thesis are derived directly from Monod-Wyman-Changeux (MWC) theory. It was originally developed to describe the cooperative allosteric transitions of biological molecules, including the archetypal sharp transition of oxygen binding to hemoglobin. It is a two-state theory, which is appropriate for highly ordered and constrained biological molecules. The theory’s central concept is that of a competition between the conformational state of the molecule and its ligand binding energy. Considering acid-base equilibria as the binding of H+ or OH- ions, we are able to describe the ionization of HPEs in solution under this framework. For HPEs the driving force for the cooperative transitions becomes the competition between the hydrophobic energy of the chain and the ionization energy of the acidic or basic groups.
One of the HPE systems that exhibits the sharpest transitions with respect to the pH of the solution, is the micellization of hydrophilic-HPE diblock copolymers. Using previous literature we demonstrate that these transitions occur cooperatively, with a high degree of correlation between the ionization state and the conformational state of the polymer.
We then introduce an experimental two-phase oil and water system which we employ to observe HPE partitioning transitions. The aim is for the system to constrain the possible conformations of the polymer chain, without the need for complicated polymer architectures. We show that a homopolymeric HPE presents sharp, cooperative transitions in such a system.
HPEs are known to interact with phospholipid membranes depending on the pH of the solution. We can identify three main environments for the HPEs in such a system. State (1), where both the polymer and membranes are freely dissolved in solution, state (2) where the polymer has dissolved the membranes into nanometre sized disks, and state (3) where the polymer inserts itself into the hydrophobic core of the membrane but the general structure of the vesicle remains intact. We analyse literature data presenting HPE-membrane interactions and show that these transitions are also consistent with the proposed cooperative model .
Overall, we aim for the contextualization of the sharp, pH-driven ionization transitions of HPEs under the general MWC family of transitions, to be a useful addition to the body of literature surrounding this class of polyelectrolyte, and aid in their use in a variety of practical applications.