Folding Polymers with Pendant Hydrogen Bonding Motifs in Water: The Effect of Polymer Length and Concentration on the Shape and Size of Single-Chain Polymeric Nanoparticles

Abstract

A set of random copolymers based on a benzene-1,3,5-tricarboxamide functional methacrylate (BTAMA) and oligoethylene glycol methacrylate (oEGMA) with different degrees of polymerization (DP, from 110 to 450) and a 10 mol % loading of BTAMA were prepared using RAFT polymerizations. The pendant BTA units encode for the formation of helical aggregates via 3-fold hydrogen bonding while the oligoethylene glycol side chains provide solubility in water. The copolymers were characterized with size exclusion chromatography, 1 H NMR spectroscopy, circular dichroism spectroscopy, light scattering, and small angle neutron and Xray scattering. In dilute aqueous solutions, the copolymers fold intramolecularly and form single chain polymeric nanoparticles (SCPNs) in water. Variable temperature CD spectroscopy showed that the cooling curves are independent of the chain length, indicating a lack of cooperativity in the folding of these copolymers. Scattering studies revealed that the SCPNs have an asymmetric shape. An increase in DP results in an increase of the aspect ratio, while the cross-sectional diameter remains the same at around 3 nm. The elongated shape of the SCPN is proposed to account for the noncooperative folding observed using CD spectroscopy, as such a shape results in a constant local BTA concentration as the copolymer increases in length.

Intramolecular Cross-Linking Methodologies for the Synthesis of Polymer Nanoparticles

“…Continuing the study on this system 4 copolymers (10:90 BTAMA:oEGMA) (P1−P4) were synthesized with DPs from 110 to 461 to understand whether folding enforced by the BTA units is dependent on chain length. 226 The overall conclusion from this study was that the polymer initial size does not affect the folding process to a great extent, and all polymers behaved similar to those previously described. In a recent contribution, critical for the understanding of the folding process in the BTA systems, Hosono et al reported "soldiers−sergeant−soldiers" (S−S−S) experiments using SCNPs with a triblock architecture, 227 taking into account that just 5% of "sergeant" (with chiral side chains) free BTA units are required to induce full chiral amplification of achiral BTA stacks.…”

A brief user's guide to single-chain nanoparticles

“…These studies reveal the potential of SCNPs but to mimic globular proteins, but the current state of the art is far from this goal. 69 Similarly shaped SCNPs were also visualized via TEM in recent work from our laboratory. 84 Cross-linking conditions typically involve dissolving the polymer in a good solvent, as poor solvation leads to aggregation.…”

“…3). [2][3][4]6,69 Alternatively, the BTA unit can be attached to a polymer via azide-alkyne "click" chemistry. The authors refer to these SCNPs as "metastable" because when cast into a film, the polymers remain soluble in chloroform; however, upon heating, the SCNPs uncoil and the UPy moieties form interchain linkages resulting in an insoluble supramolecular network.…”

“…1,2,9,72,81,82 Additionally, molecular dynamic (MD) simulations have proven useful in aiding researchers understand the data provided by small angle scattering techniques. 69 An in depth analysis of the folding process as a function of the chain length was obtained through the use of SANS, SAXS, and DLS. 81 In a recent publication by O'Reilly and coworkers, large R g values were obtained using SANS while AFM and TEM provided a more compact image with a smaller size predicted.…”

Dynamic Single Chain Polymeric Nanoparticles: From Structure to Function

“…Therefore, scattering techniques proved to be crucial to elucidate the single chain character in the BTA-based water-soluble systems. In recent studies, Gillissen et al combined spectroscopy and small-angle neutron scattering to unravel the relation between interchain self-assembly and the polymer conformation (39,44). For the first time, SANS experiments revealed the asymmetric shape of these SCPNs with a constant cross section, R cs , and variable length, L, with L > R cs (Figure 3).…”