The Coil-to-Globule Transition of Single-Chain Polymeric Nanoparticles with a Chiral Internal Secondary Structure

Abstract

The intramolecular folding of chiral single polymeric chains into single-chain polymeric nanoparticles (SCPNs) via π-stacking was investigated. To this end, hydrophilic polymers grafted with structuring, chiral 3,3′-bis(acylamino)-2,2′-bipyridine-substituted benzene-1,3,5-tricarboxamides (BiPy-BTAs) units were prepared via ring-opening metathesis polymerization (ROMP). A combination of spectroscopic and scattering techniques was employed to obtain a better understanding of the folding behavior and the chiral internal structure of these systems. Circular dichroism spectroscopy showed that the folding of the polymer is highly dependent on the solvent quality and temperature. The folding process in water was finetuned via the addition of a good cosolvent (tetrahydrofuran), resulting in an optimal balance between the conformational freedom of the polymer's backbone and the stability of the π-stacked units. Small-angle X-ray scattering (SAXS) experiments showed that the shape of the SCPNs is controlled by the formation of a chiral internal secondary structure. ■ INTRODUCTIONReproducing the specific way in which Nature folds its linear polymers into perfectly defined nanostructures by using synthetic systems is a major goal in the field of synthetic macromolecular design. A new route to obtain such structures makes use of precisely engineered polymers to construct singlechain polymeric nanoparticles (SCPNs). 1−6 In this biomimetic approach, linear polymers are folded into nanometer-sized objects via intramolecular cross-links between the polymer's cross-linkable grafts. So far, several types of intramolecular cross-links have been explored, ranging from covalent 7−13 to dynamic covalent 14−17 to noncovalent. 18−27 The structure-forming elements are usually attached as side chains to a linear polymer backbone either via direct copolymerization or by postfunctionalization. 7,15,28−30 The introduction of click chemistry 31,32 and advances in the field of synthetic polymer chemistry, 33−36 introducing robust controlled/living polymerization techniques tolerant toward functional groups, have both been crucial to obtain tailored polymeric chains, which resulted in the flourishing field of SCPNs. The modular nature of the single chain approach allows the design of nanoparticles that have potential in various applications via the implementation of specific active groups. Rudimentary enzyme analogues have already been prepared using SCPNs, by incorporation of catalytically active groups in the foldable polymer chain. 37−42 Furthermore, SCPNs functioning as chemosensors, contrast agents, and drug carriers have been prepared. 13,43−46 Since structure and function are closely related, we studied in detail how a polymer with pendant, hydrogen-bond-based supramolecular motifs folds into a SCPN in organic solvents and in water. 20,23,27,37 In a recent study, we investigated the shape and size of SCPNs in water and assessed the effect of temperature and cosolvent on their formation. 47 In the research presented here, we extend thi...

Synthesis of Sequence-Controlled Multiblock Single Chain Nanoparticles by a Stepwise Folding–Chain Extension–Folding Process

“…The presence of hydrogen bonds can also be shown by the difference between 1 H NMR spectra measured in DMSO-d 6 and CDCl 3 ( Figure 2B). In contrast to DMSO, chloroform is not an H-bonds competitor solvent.…”

“…3 Reproducing the specific way in which bio-macromolecules fold their linear polymeric chains into perfectly defined nanostructures is a major, yet, challenging goal in the field of macromolecular synthesis. [5][6][7] Inspired by this model of biopolymers, folding a single linear polymer chain into a single chain nanoparticle (SCNP) has been recognized as a robust strategy for the construction of biopolymeric nanoparticles with potential applications in catalysis, sensing or biotechnology. [8][9][10][11][12][13][14] Although the design and synthesis of single chain objects has recently received great attention, 15 the development in this field is still in its initial phase.…”

Single‐Chain Folding of Synthetic Polymers: A Critical Update

“…However, AFM experiments failed to show major differences between the two polymer series. In addition, Meijer, Palmans, and co‐workers investigated the influence of structure‐forming elements such as BTA on the formation of SCNPs in substantial detail, employing a combination of scattering methods and spectroscopy . The ABA‐type triblock copolymers were designed to represent so‐called ‘Soldier–Sergeant–Soldier’ architectures.…”

Supramolecular Nanoparticles via Single-Chain Folding Driven by Ferrous Ions

“…Single‐chain folding is also an effective method to simulate biomacromolecules. Especially, to achieve single‐chain folding via intramolecular noncovalent interaction is analogous to many folding process in nature, and it is envisaged as a simple pattern to mimic the behavior of biomacromolecules such as proteins, which exist in a well‐defined secondary, tertiary, and quaternary structure, resulting from accurate molecular weight, tacticity, monomer sequence, and so forth . Diverse crosslinking strategies, including covalent bonding, dynamic covalent bonding, and supramolecular interaction, have been adopted to achieve intramolecular collapsing.…”