Improving the Folding of Supramolecular Copolymers by Controlling the Assembly Pathway Complexity

Abstract

A family of amphiphilic, heterograft copolymers containing hydrophilic, hydrophobic, and supramolecular units based on Jeffamine M-1000, dodecylamine, and benzene-1,3,5-tricarboxamide (BTA) motifs, respectively, was prepared via a postfunctionalization approach. The folding of the copolymers in water into nanometer-sized particles was analyzed by a combination of dynamic and static light scattering, circular dichroism spectroscopy, and small-angle neutron scattering. The sample preparation protocol was crucial for obtaining reproducible and consistent results, showing that only full control over the structure and pathway complexity will afford the desired folded structure, a phenomenon similar to protein folding. The results revealed that relatively small changes in the polymer’s graft composition strongly affected the intra- versus intermolecular assembly processes. Depending on the amount of the hydrophobic grafts based on either dodecyl or BTA groups, pronounced behavioral differences were observed for copolymers that comprise similar degrees of hydrophobic content. A high number of BTA grafts (>10%) resulted in the formation of multichain aggregates comprising around six polymer chains. In contrast, for copolymers comprising up to 10% BTA grafts the folding results in nanoparticles that adopt open, sparse conformations and comprise one to two polymer chains. Interestingly, predominantly single-chain polymeric nanoparticles were formed when the copolymer comprised only Jeffamine or Jeffamine and dodecyl grafts. In addition, replacing part of the BTA grafts by hydrophobic dodecyl grafts while keeping the hydrophobic content constant promoted single-chain folding and resulted in the formation of a compact, globular nanoparticle with a more structured interior. Thus, the intra- and intermolecular self-assembly pathways can be directed by carefully tuning the polymer’s hydrophilic–hydrophobic balance in combination with the number of supramolecular grafts.

Prolate and Temperature‐Responsive Self‐Assemblies of Amphiphilic Random Copolymers with Perfluoroalkyl and Polyoxyethylene Side Chains in Solution

“…[5][6][7][8] By contrast, amphiphilic random copolymers, in which the hydrophilic and hydrophobic counits are randomly distributed along the macromolecular backbone, can self-fold in a selective solvent into compact singlechain coil nanoassemblies via an intramolecular self-association process. [9][10][11][12] While the synthesis of block copolymers is generally more complicated and timeconsuming, the synthesis of random copolymers is easier, as they are typically obtained by the copolymerization of two or more monomers in a one-step procedure. Moreover, current available reversible deactivation radical polymerization (RDRP) methods enable tailored syntheses of random copolymers with high fidelity of designed structural parameters to mediate solution self-assembly.…”

Reactive Precursor Particles as Synthetic Platform for the Generation of Functional Nanoparticles, Nanogels, and Microgels

“…Self‐assembly of preformed polymers to nanostructures is another approach that gained popularity. For instance, Palmans and Meijer functionalized PPFPA precursor polymers with different hydrophilic and hydrophobic side groups and assembled them to single‐chain polymeric nanoparticles or complex supramolecular structures . Another example is the RAFT copolymerization of PFPMA and lauryl methacrylate.…”

Catalytic single-chain polymeric nanoparticles at work: from ensemble towards single-particle kinetics

“…[22][23][24] A number of techniques have been employed to investigate the BTA-based SCPNs and to improve our understanding of how their 3D structures relate to their functions. [25][26][27][28] Circular dichroism (CD) spectroscopy and scattering techniques have been utilized to study their inner structure and shape; 25,26 single-molecule force spectroscopy has been introduced to provide information on the folding kinetics and pathways. 27 Recently, Overhauser dynamic nuclear polarization NMR has been employed to investigate the local water translational diffusion dynamics at the site where catalysis would occur.…”