Enzymes are a source of inspiration for chemists attempting to create versatile synthetic catalysts. In order to arrive at a polymeric chain carrying catalytic units separated spatially, it is a prerequisite to fold these polymers in water into well-defined compartmentalized architectures thus creating a catalytic core. Herein, we report the synthesis, physical properties, and catalytic activity of a water-soluble segmented terpolymer in which a helical structure in the apolar core is created around a ruthenium-based catalyst. The supramolecular chirality of this catalytic system is the result of the self-assembly of benzene-1,3,5-tricarboxamide side chains, while the catalyst arises from the sequential ruthenium-catalyzed living radical polymerization of the different monomers followed by ligand exchange. The polymers exhibit a two-state folding process and show transfer hydrogenation in water.

We herein report the synthesis and characterization of ABA triblock copolymers that contain two complementary association motifs and fold into single-chain polymeric nanoparticles (SCPNs) via orthogonal self-assembly. The copolymers were prepared using atom-transfer radical polymerization (ATRP) and possess different pendant functional groups in the A and B blocks (alcohols in the A block and acetylenes in the B block). After postfunctionalization, the A block contains o-nitrobenzyl-protected 2-ureidopyrimidinone (UPy) moieties and the B block benzene-1,3,5-tricarboxamide (BTA) moieties. While the protected UPy groups dimerize after photoinduced deprotection of the o-nitrobenzyl group, the BTA moieties self-assemble into helical aggregates when temperature is reduced. In a two-step thermal/photoirradiation treatment under dilute conditions, the ABA block copolymer forms both BTA-based helical aggregates and UPy dimers intramolecularly. The sequential association of the two self-assembling motifs results in single-chain folding of the polymer, affording nanometer-sized particles with a compartmentalized interior. Variable-temperature NMR studies showed that the BTA and UPy self-assembly steps take place orthogonally (i.e., without mutual interference) in dilute solution. In addition, monitoring of the intramolecular self-assembly of BTA moieties into helical aggregates by circular dichroism spectroscopy showed that the stability of the aggregates is almost independent of UPy dimerization. Size-exclusion chromatography (SEC) and small-angle X-ray scattering analysis provided evidence of significant reductions in the hydrodynamic volume and radius of gyration, respectively, after photoinduced deprotection of the UPy groups; a 30-60% reduction in the size of the polymer chains was observed using SEC in CHCl(3). Molecular imaging by atomic force microscopy (AFM) corroborated significant contraction of individual polymer chains due to intramolecular association of the BTA and UPy groups. The stepwise folding process resulting from orthogonal self-assembly-induced supramolecular interactions yields compartmentalized SCPNs comprised of distinct microdomains that mimick two secondary-structuring elements in proteins.

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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.

The folding of single polymeric chains into single chain polymeric nanoparticles (SCPNs) is a unique strategy to prepare ordered structures at the nanoscopic level. Structure forming elements are attached to a polymer chain designed to fold it into a well-defined object, the SCPN. The self-assembly of these units has been investigated in great detail. However, little is known about the impact of the resulting secondary structure on the conformation of the polymer chain. Here we employ a combination of scattering methods and spectroscopy to study how pendant chiral benzene-1,3,5-tricarboxamides (BTAs) fold oligo(ethylene glycol) methyl ether methacrylate-based polymers into SCPNs. Circular dichroism spectroscopy shows that the extent of BTA self-assembly on the polymer chain in water can be fine-tuned by means of temperature and cosolvent addition (isopropanol). Small-angle neutron scattering experiments demonstrate that single polymer chains have an asymmetric shape with a constant cross section, R cs, and variable length, L, with L > R cs. The polymer chain extends and shortens in response to variations in temperature and solvent composition, which also influence the self-assembly of the BTA units. The SCPNs stretch upon association and shrink upon disassociation of the grafted supramolecular moieties.

A set of chiral, amphiphilic, self-assembling discotic molecules based on the 3,3'-bis(acylamino)-2,2'-bipyridine-substituted benzene-1,3,5-tricarboxamide motif (BiPy-BTA) was prepared. Amphiphilicity was induced into the discotic molecules by an asymmetrical distribution of alkyl and oligo(ethylene oxide) groups in the periphery of the molecules. Small-angle X-ray scattering, cryogenic transmission electron microscopy, and circular dichroism spectroscopy measurements were performed on the discotic amphiphiles in mixtures of water and alcohol at temperatures between 0 °C an 90 °C. The combined results show that these amphiphilic discotic molecules self-assemble into supramolecular fibers consisting of either one or three discotic molecules in the fiber cross-section and that the presence of water induces the bundling of the supramolecular fibers. The rich phase behavior observed for these molecules proves to be intimately connected to the mixing thermodynamics of the water-alcohol mixtures.

A library of copolymers with pendant, protected ureido-pyrimidinone (UPy) groups was prepared applying controlled polymerization techniques. The polymer backbones were based on polyacrylate, polymethacrylate, polystyrene and polynorbornene and differ in stiffness, molecular weight and the linking moiety between the backbone and the UPy group. In all cases, the percentage of protected UPy groups was kept constant. The effect of solvent on the behaviour of the polymers before and after removal of the protecting groups was evaluated in, among others, chloroform and tetrahydrofuran (THF).After deprotection of the UPy protecting group, the UPys dimerize via four-fold H-bonding in THF, inducing a collapse into single-chain polymeric nanoparticles (SCPNs), as evidenced by a combination of 1 H-NMR spectroscopy, size-exclusion chromatography and dynamic light scattering. In chloroform, on the other hand, dimerization of the UPy groups is present but interchain interactions occur as well, resulting in less-defined SCPNs. Remarkably, the flexibility of the polymer backbone, the polymer molecular weight and the nature of the linker unit all do not affect SCPN formation. In contrast, the interaction between solvent and the UPy moiety is a critical parameter for SCPN formation. For example, strong intramolecular dimerization of the UPys is observed in THF while interparticle interactions are suppressed. From this investigation we conclude that a wide variety of polymer backbones are suitable for polymer collapse via supramolecular interactions and thus allow for the formation of SCPNs but that the solvent choice is crucial to enhance intramolecular H-bonding and, at the same time, to suppress interparticle interactions.

The interplay of two subsequent aggregation processes results in a symmetry-breaking phenomenon in an achiral self-assembling system. Partially fluorinated benzene-1,3,5-tricarboxamide molecules self-assemble into a racemic mixture of one-dimensional P- and M-helical aggregates, followed by bundling into optically active higher-order aggregates or fibers.