Rational Design of Zwitterionic Polymers with Tunable Phase Separation Propensity

TL;DR

This paper introduces a method to design zwitterionic polymers that can form coacervates with predictable phase separation behavior for biomedical applications.

Contribution

A workflow combining simulations, theory, and experiments to predict and design zwitterionic polymer phase separation.

Findings

The workflow accurately predicts phase separation types in zwitterionic polymers.

Molecular simulations reveal how functional groups influence homotypic interactions and phase behavior.

Synthesized polymers validated the predictive power of the simulation-based approach.

Abstract

Zwitterionic polymers
are emerging as promising candidates
for
forming fluid-like coacervates with desirable characteristics, including
antifouling capabilities, stimulus responsiveness, and biocompatibility.
These attributes make them particularly appealing for applications
in the biomedical field, including bioseparation, biochemical analysis,
and diagnostics. However, there are currently no clear guiding principles
for predicting the phase separation behavior of zwitterionic polymers
and informing the design of novel phase-separating polymers. In this
study, we develop a workflow that combines molecular dynamics simulations,
theory, and experiments to predict the phase separation propensity
of zwitterionic polymers, as well as the material properties of the
resulting coacervates. We validate our simulation-based workflow as
a predictive tool by synthesizing new zwitterionic polymers that undergo
no phase separation, liquid–liquid phase separation, or liquid–gel
phase separation. Beyond their predictive power, we show that molecular
simulations provide insights into the attractive homotypic intermolecular
interactions mediated by distinct functional groups, rationalizing
the large differences observed between zwitterionic monomers that
exhibit minimal structural variations. Our approach provides valuable
insights into the molecular principles governing the phase separation
of distinct zwitterionic polymers, with important implications for
the design of their materials.

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