Stepwise Unfolding of Single-Chain Nanoparticles by Chemically Triggered Gates.

The orthogonal, stepwise, and order-independent unfolding of single-chain nanoparticles (SCNPs) is introduced as a key step towards actively controlling the folding dynamics of SCNPs. The SCNPs are compacted by multiple hydrogen bonds and host-guest interactions. Well-defined diblock (AB) and tetrablock (ABCD) copolymers are equipped with orthogonal recognition motifs via modular ligation along the lateral chain. Initially, single-chain folding of the diblock copolymer was induced by the host-guest complexation of benzo-21-crown-7 (B21C7, host) and a secondary ammonium salt (AS, guest), representing an efficient avenue for single-chain collapse. Next, both orthogonal Hamilton wedge (HW) and cyanuric acid (CA) as well as B21C7-AS motifs were employed to generate SCNPs based on the ABCD polymer system. Subsequently, the stepwise dual-gated and order-independent unfolding of the SCNPs was investigated by the addition of external stimuli. The folding and unfolding were explored by 1D (1) H NMR spectroscopy, dynamic light scattering (DLS), and diffusion-ordered NMR spectroscopy (DOSY).

Single-Chain Folding of Synthetic Polymers: A Critical Update.

The current contribution serves as a critical update to a previous feature article from us (Macromol. Rapid Commun. 2012, 33, 958-971), and highlights the latest advances in the preparation of single chain polymeric nanoparticles and initial-yet promising-attempts towards mimicking the structure of natural biomacromolecules via single-chain folding of well-defined linear polymers via so-called single chain selective point folding and repeat unit folding. The contribution covers selected examples from the literature published up to ca. September 2015. Our aim is not to provide an exhaustive review but rather highlight a selection of new and exciting examples for single-chain folding based on advanced macromolecular precision chemistry. Initially, the discussion focuses on the synthesis and characterization of single-chain folded structures via selective point folding. The second part of the feature article addresses the folding of well-defined single-chain polymers by means of repeat unit folding. The current state of the art in the field of single-chain folding indicates that repeat unit folding-driven nanoparticle preparation is well-advanced, while initial encouraging steps towards building selective point folding systems have been taken. In addition, a summary of the-in our view-open key questions is provided that may guide future biomimetic design efforts.

Entropy-Driven Selectivity for Chain Scission: Where Macromolecules Cleave.

We show that, all other conditions being equal, bond cleavage in the middle of molecules is entropically much more favored than bond cleavage at the end. Multiple experimental and theoretical approaches have been used to study the selectivity for bond cleavage or dissociation in the middle versus the end of both covalent and supramolecular adducts and the extensive implications for other fields of chemistry including, e.g., chain transfer, polymer degradation, and control agent addition are discussed. The observed effects, which are a consequence of the underlying entropic factors, were predicted on the basis of simple theoretical models and demonstrated via high-temperature (HT) NMR spectroscopy of self-assembled supramolecular diblock systems as well as temperature-dependent size-exclusion chromatography (TD SEC) of covalently bonded Diels-Alder step-growth polymers.

Macromolecular surface design: photopatterning of functional stable nitrile oxides.

The efficient trapping of photogenerated thioaldehydes with functional shelf-stable nitrile oxides in a 1,3-dipolar cycloaddition is a novel and versatile photochemical strategy for polymer end-group functionalization and surface modification under mild and equimolar conditions. The modular ligation in solution was followed in detail by electrospray ionization mass spectrometry (ESI-MS). X-ray photoelectron spectroscopy (XPS) was employed to analyze the functionalized surfaces, whereas time-of-flight secondary-ion mass spectrometry (ToF-SIMS) confirmed the spatial control of the surface functionalization using a micropatterned shadow mask. Polymer brushes were grown from the surface in a spatially confined regime by surface-initiated atom transfer radical polymerization (SI-ATRP) as confirmed by TOF-SIMS, XPS as well as ellipsometry.

Entropic Effects on the Supramolecular Self-Assembly of Macromolecules.

We report the transfer of entropic chain length effects into the realm of supramolecular chemistry and thereby demonstrate a macromolecular method to tune the reaction equilibria of hydrogen bonding motifs via the application of substituents of differing lengths and masses while not altering the actual recognition units to achieve a difference in the degree of association. The supramolecular adducts are characterized via temperature-dependent nuclear magnetic resonance (NMR) spectroscopy.

Reversible single-chain selective point folding via cyclodextrin driven host-guest chemistry in water.

In the present communication we introduce a new platform technology for the reversible folding of single polymer chains in aqueous environment on the basis of cyclodextrin (CD) host-guest chemistry and controlled radical polymerization protocols. The single-chain folding of adamantyl-ß-CD α-ω-functionalized poly(N,N-dimethylacrylamide) and its reversion at elevated temperatures were monitored by DLS and nuclear Overhauser enhancement spectroscopy (NOESY).

π-conjugated polymer-fullerene covalent hybrids via ambient conditions Diels-Alder ligation.

The established ability of graphitic carbon-nanomaterials to undergo ambient condition Diels-Alder reactions with cyclopentadienyl (Cp) groups is herein employed to prepare fullerene-polythiophene covalent hybrids with improved electron transfer and film forming characteristics. A novel precisely designed polythiophene (M n 9.8 kD, D 1.4) with 17 mol% of Cp-groups bearing repeat unit is prepared via Grignard metathesis polymerization. The UV/Vis absorption and fluorescence (λex 450 nm) characteristics of polythiophene with pendant Cp-groups (λmax 447 nm, λe-max 576 nm) are comparable to the reference poly(3-hexylthiophene) (λmax 450 nm, λe-max 576 nm). The novel polythiophene with pendant Cp-groups is capable of producing solvent-stable free-standing polythiophene films, and non-solvent assisted self-assemblies resulting in solvent-stable nanoporous-microstructures. (1) H-NMR spectroscopy reveals an efficient reaction of the pendant Cp-groups with C60 . The UV/Vis spectroscopic analyses of solution and thin films of the covalent and physical hybrids disclose closer donor-acceptor packing in the case of covalent hybrids. AFM images evidence that the covalent hybrids form smooth films with finer lamellar-organization. The effect is particularly remarkable in the case of poorly soluble C60 . A significant enhancement in photo-voltage is observed for all devices constituted of covalent hybrids, highlighting novel avenues to developing efficient electron donor-acceptor combinations for light harvesting systems.

Ambient temperature catalyst-free light-induced preparation of macrocyclic aliphatic polyesters.

The light induced, catalyst-free ambient temperature preparation of macrocyclic aliphatic polyesters is pioneered. Based on the photo-induced Diels-Alder reaction of orthoquinodimethane and acrylate moieties, cyclic polyesters of high purity are readily synthesized. Considering the high tolerance to functional groups and the orthogonality of the ligation, the reported protocol can be easily transferred to a large range of polymers, complex topologies (tadpole, sun-shaped, jellyfish, etc.) and applications.

Single-chain self-folding of synthetic polymers induced by metal-ligand complexation.

The controlled folding of a single polymer chain is for the first time realized by metal- complexation. α,ω-Bromine functional linear polymers are prepared via activators regenerated by electron transfer (ARGET) ATRP (M¯n,SEC = 5900 g mol(-1) , D = 1.07 and 12 000 g mol(-1) , D = 1.06) and the end groups of the polymers are subsequently converted to azide functionalities. A copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is carried out in the presence of a novel triphenylphosphine ligand and the polymers to afford homotelechelic bis-triphenylphosphine polymeric-macroligands (MLs) (M¯n,SEC = 6600 g mol(-1) , D = 1.07, and 12 800 g mol(-1) , D = 1.06). Single-chain metal complexes (SCMCs) are formed in the presence of Pd(II) ions in highly diluted solution at ambient temperature. The results derived via (1) H and (31) P{(1) H} NMR experiments, SEC, and DLS unambiguously evidence the efficient formation of SCMCs via metal ligand complexation.

Facile Preparation of Supramolecular H-Shaped (Ter)polymers via Multiple Hydrogen Bonding.

A well-defined Hamilton wedge (HW) midchain functionalized block copolymer, i.e., polyethylene glycol-b-polystyrene (PEG-HW-PS, Mn,GPC = 5600 Da, PDI = 1.03), was successfully synthesized via a combination of atom transfer radical polymerization (ATRP) and copper-catalyzed azide alkyne cycloaddition (CuAAC). An α,ω-cyanuric acid (CA) difunctional linear homopolymer poly(n-butylacrylate) (CA-PnBA-CA, Mn,GPC = 8100 Da, PDI = 1.09) was concomitantly prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization. Supramolecular H-shaped macromolecules were-for the first time-prepared through supramolecular self-assembly between HW and CA recognition motifs to generate (PS-b-PEG)·PnBA·(PS-b-PEG) and (PS-b-PS)·PnBA·(PS-b-PS) in CH2Cl2 or dichloromethane-d2 at ambient temperature. The self-assembly process (at a total concentration of the two species of close to 4.5 mM) was evidenced by proton nuclear magnetic resonance (1H NMR) spectroscopy, diffusion-ordered NMR spectroscopy (DOSY), and dynamic light scattering (DLS) analyses. The results derived via DOSY NMR experiments and DLS combined with a Job plot analysis and in-depth NMR titration experiments indicate that the formation of supramolecular H-shaped macromolecules in 2:1 stoichiometry is efficiently occurring via the employed complementary recognition motifs with high binding constants (between 1.2 and 1.5 × 105 L mol-1 at ambient temperature).

Combining modular ligation and supramolecular self-assembly for the construction of star-shaped macromolecules.

A well-defined random copolymer of styrene (S) and chloromethylstyrene (CMS) featuring lateral chlorine moieties with an alkyne terminal group is prepared (P(S-co-CMS), M(n) = 5500 Da, PDI = 1.13). The chloromethyl groups are converted into Hamilton wedge (HW) entities (P(S-co-HWS), M(n) = 6200 Da, PDI = 1.13). The P(S-co-HWS) polymer is subsequently ligated with tetrakis(4-azidophenyl)methane to give HW-functional star-shaped macromolecules (P(S-co-HWS))(4), M(n) = 25,100 Da, PDI = 1.08). Supramolecular star-shaped copolymers are then prepared via self-assembly between the HW-functionalized four-arm star-shaped macromolecules (P(S-co-HW))(4) and cyanuric acid (CA) end-functionalized PS (PS-CA, M(n) = 3700 Da, PDI = 1.04), CA end-functionalized poly(methyl methacrylate) (PMMA-CA, M(n) = 8500 Da, PDI = 1.13) and CA end-functionalized polyethylene glycol (PEG-CA, M(n) = 1700 Da, PDI = 1.05). The self-assembly is monitored by (1)H NMR spectroscopy and light scattering analyses.

Single chain folding of synthetic polymers by covalent and non-covalent interactions: current status and future perspectives.

The present feature article highlights the preparation of polymeric nanoparticles and initial attempts towards mimicking the structure of natural biomacromolecules by single chain folding of well-defined linear polymers through covalent and non-covalent interactions. Initially, the discussion focuses on the synthesis and characterization of single chain self-folded structures by non-covalent interactions. The second part of the article summarizes the folding of single chain polymers by means of covalent interactions into nanoparticle systems. The current state of the art in the field of single chain folding indicates that covalent-bond-driven nanoparticle preparation is well advanced, while the first encouraging steps towards building reversible single chain folding systems by the use of mutually orthogonal hydrogen-bonding motifs have been made.

Synthesis of terpolymers by click reactions.

Well-defined polymeric structures were easily generated through living polymerization systems, in particular, living radical polymerizations. The polymeric precursors with orthogonal functionalities were subsequently clicked together with single or double (combinatorial) click reactions, such as the copper-catalyzed azide-alkyne cycloadditions (CuAAC) and Diels-Alder reactions, to create a wide variety of linear and nonlinear terpolymers.

Nitrone-mediated radical coupling reactions: a new synthetic tool exemplified on dendrimer synthesis.

A synthetic strategy employing nitrones as radical spin traps is presented on the example of the efficient generation of novel dendrimers via a combination of radical and classical 'click' chemistry.

Single chain self-assembly: preparation of alpha,omega-donor-acceptor chains via living radical polymerization and orthogonal conjugation.

Alpha,omega-hydrogen donor/acceptor functional polymer strands are prepared via a combination of living radical polymerization and orthogonal conjugation and subsequently self-assembled as single chains to emulate--on a simple level--the self-folding behaviour of natural biomacromolecules.