Heterogeneous Charged Complexes of Random Copolymers for the Segregation of Organic Molecules

Abstract

Nature harnesses the disorder of intrinsically disordered proteins to organize enzymes and biopolymers into membraneless organelles. The heterogeneous nature of synthetic random copolymers with charged, polar, and hydrophobic groups has been exploited to mimic intrinsically disordered proteins, forming complexes with enzymatically active proteins and delivering them into nonbiological environments. Here, the properties of polyelectrolyte complexes composed of two random copolymer polyelectrolytes are studied experimentally and via simulation with the aim of exploiting such complexes for segregating organic molecules from water. The anionic polyelectrolyte contains hydrophilic and hydrophobic side chains and forms self-assembled hydrophobic domains. The cationic polymer is a high-molecular-weight copolymer of hydrophilic and charged side groups and acts as a flocculant. We find that the polyelectrolyte complexes obtained with this anionic and cationic random copolymer system are capable of absorbing small cationic, anionic, and hydrophobic organic molecules, including perfluorooctanoic acid, a compound of great environmental and toxicologic concern. Importantly, these macroscopic complexes can be easily removed from water, thereby providing a simple approach for organic contaminant removal in aqueous media. MARTINI and coarse-grained molecular dynamics simulations explore how the microscale heterogeneity of these random copolymer complexes relates to their segregation functionality.

Sequence Design of Random Heteropolymers as Protein Mimics

“…RHPs can have batch-to-batch variations but cannot yet be sequenced with monomeric specificity. Despite key differences, several computational and experimental studies have demonstrated the ability for RHPs to recapitulate protein-like behaviors. − Unlike sequence-specific heteropolymers, − the lack of RHP sequence information significantly hampers our ability to further leverage the full potential of this unique class of polymers for precisely tailored functionality. Synthetic breakthroughs in reversible-deactivation radical polymerization (RDRP) have made it possible to synthesize heteropolymers with improved reproducibility and control over the probability of each monomer along the polymer chain. − This narrows the gap between theoretically ideal polymerization and synthesized heteropolymers.…”

Functional enzyme–polymer complexes

“…An alternative hypothesis is that the random copolymers interact favorably with the substrate, leading to an increase in local substrate concentration. Indeed, it has been shown that these random copolymers can bind hydrophobic small molecules ( 41 ) and that IDRs in proteins, similar to the random copolymers in Fig. 4 B , promote higher-order assembly ( 62 ).…”

“…Due to their methyl methacrylate backbone, they are inexpensive to randomly polymerize in large-scale, industrial processes. They have also been used in previous computational and experimental studies of polymer complexes with proteins including horseradish peroxide, glucose oxidase, and organophosphorus hydrolase as well as small organic molecules ( 32 , 41 ). Further, amphiphilic random copolymers are well suited to complex with the heterogeneous polar and nonpolar surfaces of proteins ( 42 ) including PETase.…”

A Modeling-Based Design to Engineering Protein Hydrogels with Random Copolymers

“…More recently, a combined experimental and modeling approach has been developed in our group to segregate organic molecules in water by using polyelectrolyte complexes composed of random copolymers. 22 Clearly, the chemical diversity of protein surface patterns and the experimental challenges of tailored polymer design often prevent the development of general and sustainable protocols for an effective protein coassembly with random copolymers. Therefore, although some attempts have manifested promising scenarios, the prediction of the enzyme−random copolymer self-assembly conformation based on their physical-chemistry properties remains a challenge.…”

“…Successful results in this direction have been obtained by Panganiban and co-workers who presented an efficient design approach of random heteropolymers based on protein surface patches while maintaining the enzymatic activity in a foreign environment. More recently, a combined experimental and modeling approach has been developed in our group to segregate organic molecules in water by using polyelectrolyte complexes composed of random copolymers . Clearly, the chemical diversity of protein surface patterns and the experimental challenges of tailored polymer design often prevent the development of general and sustainable protocols for an effective protein coassembly with random copolymers.…”