Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

This dissertation investigates how precise polymer synthesis and molecular engineering govern liquid–liquid phase separation (LLPS), coacervation, and hierarchical phase organization by developing well-defined peptide-, peptoid-, and polyacrylamide-based polymer systems. Controlled polymerization techniques were employed to systematically vary backbone chirality, charge-block architecture, side-chain chemistry, and initiator structure while maintaining precise control over molecular weight, composition, and architecture. Comprehensive structural characterization enabled direct correlations between polymer structure and phase behavior.

Chapter 2 describes the synthesis and characterization of peptide- and peptoid-based polyelectrolytes possessing systematically varied backbone chirality using controlled N-carboxyanhydride (NCA) ring-opening polymerization. Well-defined homochiral, racemic, and achiral polymer libraries were prepared to investigate the influence of stereochemistry on complex coacervation. The deviation from maximum complexation at a one-to-one charge ratio suggested that factors beyond electrostatics influence complexation. Homochiral polypeptides formed β-sheet-mediated precipitates, whereas mixed-chiral and achiral systems consistently produced liquid coacervates, establishing chirality as one of the primary determinants of condensate morphology.

Chapter 3 presents an organic acid-promoted sequential NCA polymerization strategy for the efficient synthesis of sequence-controlled random, diblock, tetrablock, hexablock, and octablock polypeptoid polyampholytes. Kinetic analysis, nuclear magnetic resonance spectroscopy, and size-exclusion chromatography confirmed the living nature of polymerization with excellent molecular-weight control throughout sequential block formation. Increasing charge-block length systematically broadened the phase-separation window, lowered the critical concentration for self-coacervation, and enhanced salt resistance, experimentally validating theoretical predictions regarding charge-block architecture.

Chapter 4 describes the synthesis of functional polyacrylamide-based polyelectrolytes by reversible addition–fragmentation chain-transfer (RAFT) polymerization to investigate the molecular origins of multiphase complex coacervation. Controlled polymer synthesis and characterization enabled systematic evaluation of side-chain chemistry, demonstrating that subtle structural variations are sufficient to direct phase immiscibility, selective partitioning, and hierarchical compartmentalization within synthetic multiphase condensates.

Chapter 5 investigates the polymerization behavior of N-substituted glycine N-carboxyanhydrides initiated by mono- and multifunctional amines as a platform for the synthesis of well-defined star-shaped polysarcosine. In situ nuclear magnetic resonance spectroscopy was used to compare initiation efficiency and polymerization kinetics across a series of initiators to identify architectures capable of producing controlled multi-arm polymers. These studies establish synthetic design criteria for the preparation of well-defined polysarcosine precursors suitable for hydrogel and biomaterials applications.

Collectively, this work establishes robust synthetic methodologies for preparing precisely defined polymer model systems and demonstrates how controlled molecular architecture governs coacervation and liquid–liquid phase separation. These findings provide molecular design principles for engineering biomimetic polymers, synthetic condensates, and functional soft materials.

Date

7-17-2026

Committee Chair

Zhang, Donghui

LSU Acknowledgement

1

LSU Accessibility Acknowledgment

1

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