Folding of Sequence-Controlled Graft Copolymers to Subdomain-Defined Single-Chain Nanoparticles

Abstract

We developed a methodology, inspired by the folding of proteins, for the precision synthesis of hairy polymer nanoparticles. High-molar mass and narrowly dispersed graft copolymers were synthesized by graft-through ring opening metathesis polymerization, to incorporate a designated number of side chains and dimerizable cinnamic acid groups. Intrachain photodimerization collapsed the backbone and arrested it into a compact globular conformation, resulting in hairy nanoparticles topologically equivalent to a core cross-linked star polymer. The single-chain collapse process translates the molecular information written on the 1D graft copolymer into the 3D globular polymer nanoparticle, like protein folding. Unprecedented control over structural parameters was achieved, including the length, number, and composition of the side chains as well as cross-linking density. Different side chains formed distinct subdomains in the sterically congested nanoparticle state and further self-assembled into micellar aggregates in a selective solvent. Both experimental observations and computational simulations indicated that preorganization of the side chains in the block sequence produces subdomains which primarily follow the backbone length scale, while random sequences showed side chain-dependent scaling. Polymer nanoparticles with discrete multiple subdomains were produced by folding of the ternary block graft copolymers. Drastic differences in the self-assembly behavior of ABC-and ACBsequenced nanoparticles indicate that the spatial organization of subdomains can be achieved by sequence control.

Single-Chain Polymer Nanoparticles for Addressing Morphologies and Functions at the Nanoscale: A Review

“…Seo et al synthesized graft copolymers containing PS and PLA as side chains. 42 The authors synthesized a random (g-[PLA-ran-PS]) Recent studies on SCNPs have focused particularly on constructing chemically disparate nanodomains into the SCNP molecules. This "compartmentalization" is made possible using designed block copolymer precursors, as shown in Figure 8a.…”

“…A recent work of Seo et al elucidates the role of the grafted density of polymeric arms on the level of control of CCS polymer morphology (Figure ). In this work the authors synthesized a series of grafted random copolymers, using ROMP from a mixture of a PLA macromonomer (named PLA-N), norbornene (N), and, at fixed molar ratio of 30 mol %, a monomer containing cinnamic acid (named, cinnamic acid-N). Grafted polymers differ from each other for the grafted density of PLA vs N co-monomer, which span from 10 to 60 mol %, and designed as g-PLA­( x ), where x represents the grafted density of PLA.…”

“…(a) Synthetic scheme of c-PLA from g-PLA; (b) GPC traces of c-PLA­(x) (solid lines) and g-PLA (dashed lines); and (c) plot of V c , a parameter derived from M p of SEC of c-PLA, vs grafting density ( V c = M p(g‑PLA) – M p(c‑PLA) /M p(g‑PLA) ). Adapted with permission from ref . Copyright 2021 American Chemical Society.…”

“…Miktoarm CCS architecture of globular nanoparticles can be achieved using precise control of structural parameters such as length, number, and composition of the arms and their spatial location around the core. Seo et al synthesized graft copolymers containing PS and PLA as side chains . The authors synthesized a random (g-[PLA- ran -PS]) and block graft copolymer (g-[PLA- b -PS]) via ROMP polymerization protocols, containing 10 and 30 mol % photodimerizable cinnamic acid functionalities.…”

Salt Counterion Valency Controls the Ionization and Morphology of Weak Polyelectrolyte Miktoarm Stars

“…In the outer shell of miktoarm star-like micelles, different chain types can become separated into subdomains predominantly containing only one chain type, 5 Even in single-chain nanoparticles, individual chemical entities can be separated into subdomains. 6 Larger structures formed by more than one chain and segregated into subdomains can contain at least one well-defined patch. Through these patches, they maintain strongly anisotropic, highly directional interactions with other particles or surfaces and are thus termed patchy particles.…”