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Novel approaches to targeted cancer therapy that combine improved efficacy of current chemotherapies while minimising side effects are highly sought after. The development of single-chain polymeric nanoparticles (SCPNs) as bio-orthogonal catalysts for targeted site-specific pro-drug activation is a promising avenue to achieve this. Currently, the application of SCPNs as bio-orthogonal catalysts is in its early stages due to reduced performance when increasing the medium’s complexity. Herein, we present a systematic approach to identify the various aspects of SCPN-based catalytic systems, to improve their efficiency in future in-vitro/in-vivo studies. We developed amphiphilic polymers with a polyacrylamide backbone, and functionalised with the Pd(II)-binding ligands triphenylphosphine and bipyridine. The resulting polymers collapse into small-sized nanoparticles (5-6 nm) with an inner hydrophobic domain that comprises the Pd(II) catalyst. We systematically evaluated the effect of polymer microstructure, ligand-metal complex, and substrate hydrophobicity on thecatalytic activity of the nanoparticles for depropargylation reactions in water, PBS or DMEM. The results show that the catalytic activity of nanoparticles is primarily impacted by the ligand-metal complex while polymer microstructure has aminor influence. Moreover, the rate of reaction is increased for hydrophobic substrates. In addition, Pd(II) leaching studies confirmed little to no loss of Pd(II) from the hydrophobic interior which can reduce off-target toxicities in future applications. Careful deconstruction of the catalytic system revealed that covalent attachment of the ligand to the polymer backbone is necessary to retain its catalytic activity in cell culture medium while not in water. Finally, we activated anti-cancer pro-drugs based on 5-FU, paclitaxel, and doxorubicin using the best-performing catalytic SCPNs. We found that the rate of pro-drugactivation in water accelerated efficiently by catalytic SCPNs, whereas in in cell culture medium the results dependened on the type of protecting group and hydrophobicity of the prodrug. We believe our findings will aid in the development of suitable catalytic systems and pro-drugs for future in-vivo applications

Controlling the reciprocity between chemical reactivity and supramolecular structure is a topic of great interest in the emergence of molecular complexity. In this work, we investigate the effect of a covalent reaction as a trigger to depolymerize a supramolecular assembly. We focus on the impact of an in situ thiol–ene reaction on the (co)polymerization of three derivatives of benzene-1,3,5-tricarboxamide (BTA) monomers functionalized with cysteine, hexylcysteine, and alkyl side chains: Cys-BTA, HexCys-BTA, and a-BTA. Long supramolecular polymers of Cys-BTA can be depolymerized into short dimeric aggregates of HexCys-BTAvia the in situ thiol–ene reaction. Analysis of the system by time-resolved spectroscopy and light scattering unravels the fast dynamicity of the structures and the mechanism of depolymerization. Moreover, by intercalating the reactive Cys-BTA monomer into an unreactive inert polymer, the in situ thiol–ene reaction transforms the intercalator into a sequestrator and induces the depolymerization of the unreactive polymer. This work shows that the implementation of reactivity into supramolecular assemblies enables temporal control of depolymerization processes, which can bring us one step closer to understanding the interplay between non-covalent and covalent chemistry., We report on the controlled depolymerization of supramolecular 1D polymers into well-defined dimers triggered by a covalent reaction on the side chains of the monomer.

Macromolecules found in Nature display a precise control over the primary as well as higher ordered architectures. To mimic the folding found in Nature, we herein demonstrate the design and characterization of single-chain nanoparticles that are formed by the folding of sequence-defined macromolecules with metal ions. The study showcases the influence of the loop size of such precision macromolecules on their relative hydrodynamic radius. The sequence-defined structures are fabricated using thiolactone chemistry, where two picolyl moieties are installed forming a valuable ligand system for subsequent metal complexation. Next, metal ions such as Ni(ii) and Cu(ii) ions are introduced to fold the unimers into sequence-defined single-chain nanoparticles (SD-SCNPs). After proving the successful complexation using a trimer, a systematic study is conducted altering the distance between the respective ligands by incorporating variable numbers of non-functionalized spacer units. Finally, the loop size formation of the SD-SCNPs is evidenced by DOSY measurements. The result indicates that the positioning of the ligands plays a crucial role on the compaction process and, more specifically, on the final size of the SD-SCNP. In addition, molecular dynamics (MD) simulations show the effects of the sequence and Ni(ii) complexation on the structure and compaction of the SD-SCNPs, and highlight the differences of the nanoparticles' shape when varying the number of spacer units. Finally, the system is further expanded to a dodecamer and even a heptadecamer with drastically decreased hydrodynamic radii after compaction.

In contrast to biomacromolecules, synthetic polymers generally lack a defined monomer sequence, therefore one of the challenges of polymer chemists these days is gaining more control over the primary structure of synthetic polymers and oligomers. In this work, stereocontrolled sequence-defined oligomers were synthesised using a thiolactone-based platform. Step-wise elongation of the oligomer occurs via ring-opening of the thiolactone, resulting in the formation of stereocenters along the backbone. These initial studies indicate remarkable differences in the strength of non-covalent interactions in isotactic and atactic oligomers. Different side-chain moieties were introduced using alkyl halide building blocks and the synthetic protocol was succesfully optimised and automated. Furthermore, the possible post-synthesis modification of the oligomers was demonstrated using 'click' chemistry.

Non-covalently crosslinked polymeric networks are promising materials towards sustainable and recyclable plastics. Here, we present the post-functionalization of poly(dimethyl siloxane) (PDMS) with supramolecular moieties, attached as grafts to the PDMS backbone, to obtain recyclable PDMS networks. We select three different supramolecular motifs that differ in interaction strength and investigate how these differences affect the dynamic behavior of the networks. The introduction of dinitrohydrazones (hydz), which afford weak supramolecular interactions by π-stacking, resulted in a viscous material at room temperature. Stronger self-association was achieved by the introduction of benzene-1,3,5-carboxamides (BTAs) and ureidopyrimidinones (UPys), which self-assemble via triple and quadruple hydrogen bonding, respectively. This resulted in a thermoplastic elastomeric material for BTA-based PDMS and brittle materials for Upy-based PDMS. Time- and temperature-dependent mechanical measurements reveal that the dynamic nature of the supramolecular bonds becomes slower upon increasing the interaction strength. The polymers are fully recyclable by solvation or compression molding without the loss of material properties. Thereby, by using one linear PDMS backbone, we demonstrate how fundamentally different material properties are obtained by changing the supramolecular interaction strength and type of non-covalent crosslinks. These molecular insights broaden the scope and application of PDMS-based sustainable materials.

Adjusting the length, composition, and microstructure of a polymer during the process of its formation in principle allows achieving the desired properties, thereby enabling custom-design of the thus generated polymer for its targeted function. Over the past years, different stimuli have been applied to manipulate responsive catalyst systems in situ; among them light takes center stage as perhaps the most promising stimulus. Here, we highlight recent progress in the area of photoswitchable polymerization catalysis. In particular, we focus on the challenge of combining photoswitchable and catalytically active units in a manner that both entities are somehow coupled and interact, yet also retaining their switching and catalysis functions under suitable conditions. We introduce the requirements for an ideal case of a photoswitchable polymerization catalyst system and use them to analyze the current state of the art. Based on our analysis of the status quo, we point to scientific challenges in the field and sketch perspectives including potential applications.

This work deals with the use of 2-cyano-2-arylpropanoic acids as chemical fuels for an acid-base operated molecular switch that consists of a Sauvage-type catenand composed of two identical macrocycles incorporating a phenanthroline unit. When used as a base promoter of the decarboxylation of propanoic acid derivatives, the switch undergoes large amplitude motion from the neutral catenand to a protonated catenate and back again to the neutral state. The rate of back proton transfer, which determines the rate of the overall process, was markedly affected by para-substituents in the order Cl > H > CH3 > OCH3 (ρ = +5.2). Thus, the time required to complete a full cycle was almost two days for the OCH3 derivative and dropped to a few minutes for the Cl derivative. These results show for the first time that the rate of operation of a molecular switch can be regulated by variations in the fuel structure.

A new class of discrete-length block co-oligomers comprising oligodimethylsiloxane (oDMS) and oligomethylene (oM) is presented. For this, oM blocks containing up to 69 backbone carbons are synthesised via an iterative, Wittig reaction-based strategy. Ligation with oDMS hydrides permits the formation of a library of block co-oligomers (BCOs) in which the block configuration, MW, and composition can be tuned. Differential scanning calorimetry and small-angle X-ray scattering show that all BCOs exhibit microphase separation into well-ordered lamellar morphologies, driven by the crystallisation of the oM blocks. Pre-melting order-order transitions are present for a number of BCOs, resulting in an alteration of the oM crystal packing as well as in changes of the overall microphase-segregated structure. As a result of the discrete nature of the BCO chains, we propose models that describe the molecular organisation within the microphase-segregated structures by evaluating the changes in the lamellar thickness upon varying the BCO architecture.

Understanding interfacial phenomena in soft materials such as wetting, colloidal stability, coalescence, and friction warrants non-invasive imaging with nanometer resolution. Super-resolution microscopy has emerged as an attractive method to visualize nanostructures labeled covalently with fluorescent tags, but this is not amenable to all interfaces. Inspired by PAINT we developed a simple and general strategy to overcome this limitation, which we coin 'iPAINT: interface Point Accumulation for Imaging in Nanoscale Topography'. It enables three-dimensional, sub-diffraction imaging of interfaces irrespective of their nature via reversible adsorption of polymer chains end-functionalized with photo-activatable moieties. We visualized model dispersions, emulsions, and foams with ∼20 nm and ∼3° accuracy demonstrating the general applicability of iPAINT to study solid/liquid, liquid/liquid and liquid/air interfaces. iPAINT thus broadens the scope of super-resolution microscopy paving the way for non-invasive, high-resolution imaging of complex soft materials.

The mechanism of the oxidation of benzyl alcohol with iron(III)nitrate nonahydrate under conventional and under microwave heating conditions has been investigated and the reaction conditions have been optimized. A series of redox reactions leads to the formation of benzaldehyde and other products. Direct comparison between conventional and microwave heating revealed identical conversions profiles. Mastering the microwave induced heat, absence of a real microwave effect and byproduct formation are the major factors to advise a traditional batch-wise way of process development to a larger scale. © 2009 The Royal Society of Chemistry

We report on the self-assembly of two enantiomeric sexithiophenes in solution and on surfaces. Circular dichromism of aggregated sexithiophenes and drop-cast films reveals, as expected, mirror image spectra for both enantiomers. The aggregation in thin deposits from sexithiophenes molecularly dispersed in a solution on different types of substrates was investigated by atomic force microscopy (AFM). On graphite, one-dimensional objects (nanowires) are formed while on mica platelets are generated. Remarkably, we found that both enantiomers form left-handed helices on silicon. This observation depends on the hydrophilicity of the silicon. Furthermore, the achiral sexithiophene did not form helical aggregates suggesting that the stereocenter is required to obtain chirality in the fibers.

The ABA amphiphilic block copolymers, poly(hydroxyethyl methacrylate-hlock-methylphenylsilane-block-hydroxyethyl methacrylate) (PHEMA-PMPS-PHEMA) and poly[oligo(ethylene glycol) methyl ether methacrylate-block-methylphenylsilane-block-oligo(ethylene glycol). methyl ether methacrylate] (POEGMA-PMPS-POEGMA) were successfully synthesised via atom transfer radical polymerisation (ATRP). Macroinitiators suitable for the ATRP of oligo(ethylene glycol) methyl ether methacrylate and 2-hydroxyethyl methacrylate were synthesised from the condensation reaction of alpha,omega-dihalopolymethylphenylsilane and 2'-hydroxyethyl 2-bromo-2-methylpropanoate. The copolymers were characterised using H-1 NMR and C-13 NMR spectroscopy and molecular weight characteristics were determined using size exclusion chromatography and H-1 NMR. The aggregation behaviour of some of the copolymers in water was studied using transmission and scanning electron microscopy and dynamic light scattering. These revealed the prevalent aggregate species to be micelles. Larger aggregates of 300-1000 nm diameter were also observed. The UV induced degradation of the aggregates was studied by UV-Vis spectroscopy. The thermal behaviour of selected copolymers was studied by differential scanning calorimetry and microphase separation of the two components was demonstrated.

Evaporative self-assembly of dilute solutions containing single-chain polymeric nanoparticles results in characteristic morphologies imaged using atomic force microscopy. Quantitative comparison of experimental data to morphologies obtained by lattice-gas simulations shows that the nonequilibrium patterns emerge from a complex interplay between dewetting, solvent evaporation and nanoparticle diffusion.

The molecular origin of the isotope-induced diastereomeric enrichment in helical supramolecular polymers consisting of trialkylbenzene-1,3,5-tricarboxamides (BTAs) is studied using plane-wave DFT calculations. We demonstrate that the creation of a chiral center at the a-position of the alkyl chains of a BTA by H–D exchange leads to a small but notable preference for the formation of supramolecular hydrogen bonded structures with a particular helicity. The bias for one helical sense preference is caused by the orientation of the vibrational eigenmodes of the C–H and C–D stretching frequencies at the chiral center and by hyperconjugative destabilization of the anti C–H orbital.

Precise control over folded conformations of synthetic polymers is highly desirable in the development of functional nanomaterials for diverse applications. Introducing monomers capable of strong intramolecular hydrogen bonding is a promising route to achieve this control. In the present work we report the use of Wang–Landau Monte Carlo simulations of coarse-grained copolymers to explore the design parameters of these systems on their pathway to collapse. The highly directional nature of hydrogen-bonded supramolecular interactions is modelled by a directional non-bonded potential while a harmonic bending potential is used to take into account the flexibility of the polymer chain, thus making it possible to look at the interplay of both factors. The introduction of directional interactions in the copolymer chain leads to a sharper coil-globule collapse when compared to homopolymers composed of isotropic interacting beads only. Simultaneously, some of the stiffness-dependent structural properties become exacerbated when directional beads are present. Finally, from the heat capacity profiles for the different chain stiffness values we are able to distinguish the prevalence of the collapse of the backbone for highly flexible chains, while as chain stiffness increases folding of the co-polymer due to the directional interactions becomes the dominant feature.

After their first synthesis in 1915 by Curtius, benzene-1,3,5-tricarboxamides (BTAs) have become increasingly important in a wide range of scientific disciplines. Their simple structure and wide accessibility in combination with a detailed understanding of their supramolecular self-assembly behaviour allow full utilization of this versatile, supramolecular building block in applications ranging from nanotechnology to polymer processing and biomedical applications. While the opportunities in the former cases are connected to the self-assembly of BTAs into one-dimensional, nanometer-sized rod like structures stabilised by threefold H-bonding, their multivalent nature drives applications in the biomedical field. This review summarises the different types of BTAs that appeared in the recent literature and the applications they have been evaluated in. Currently, the first commercial applications of BTAs are emerging. The adaptable nature of this multipurpose building block promises a bright future.

The transfer of the cooperative self-assembled fibrils to a gold substrate has been studied by means of scanning probe microscopy techniques revealing the crucial role of the early formation of a monolayer.

Preferred handedness in the supramolecular chirality of self-assembled achiral oligo(p-phenylenevinylene) (OPV) derivatives is induced by chiral solvents and spectroscopic probing provides insight into the mechanistic aspects of this chiral induction through chiral solvation.

A protease-activatable collagen targeting probe (proCNA35) is synthesized by conjugation of a synthetic collagen fragment to the collagen binding protein CNA35 via a protease-cleavable linker. Cleavage of the linker by MMP1 releases the intramolecular inhibition of the collagen binding site and restores its collagen binding capacity.

A detailed study regarding the influence of microwave irradiation on the formation of a series of Grignard reagents in terms of rates and selectivities has revealed that these heterogeneous reactions may display a beneficial microwave effect. The interaction between microwaves and magnesium turnings generates violent electrostatic discharges. These discharges on magnesium lead to melting of the magnesium surface, thus generating highly active magnesium particles. As compared to conventional operation the microwave-induced discharges on the magnesium surface lead to considerably shorter initiation times for the insertion of magnesium in selected substrates (i.e. halothiophenes, halopyridines, octyl halides, and halobenzenes). Thermographic imaging and surface characterization by scanning electron microscopy showed that neither selective heating nor a "specific" microwave effect was causing the reduction in initiation times. This novel and straightforward initiation method eliminates the use of toxic and environmentally adverse initiators. Thus, this initiation method limits the formation of by-products. We clearly demonstrated that microwave irradiation enables fast Grignard reagent formation. Therefore, microwave technology is promising for process intensification of Grignard based coupling reactions.

Extended core discotic molecules self-assemble in water by different secondary interactions to give well-defined, helical columns in which the chirality of one chiral molecule is transferred to on average 12 achiral molecules.

An odd–even effect is observed in the CD spectra of a homologous series of aggregated optically active poly(3,4-dialkoxythiophene)s, suggesting a helical packing of polymer chains into chiral superstructures, similar to that of the cholesteric liquid crystalline phase.

Amphiphilic gold nanoparticles decorated with ethyleneoxide and oligo(p-phenylene vinylene) ligands self-assemble into disc-shaped objects.

Fluorescence spectroscopy and atomic force microscopy (AFM) measurements using bisurea-pyrene probes show that they are randomly dispersed in the hard blocks of thermoplastic elastomers with matching bisurea groups, whereas they phase separate from polymers with non-matching or no bisurea groups.

Dendritic wedges with a substitution pattern that forces the growth inwards are introduced and the use of this new building strategy is exemplified in the synthesis and chiroptical properties of a chiral dendrimer.

A strategy for the synthesis of multivalent peptide-based nonsymmetric dendrimers by native chemical ligation using poly(lysine) dendritic wedges as scaffolds is presented.

N,N′ ,N″-Tris(3-pyridyl)trimesic amide, 1, forms a unique P symmetrical crystal containing pores with a mean diameter of 8.26 A.

Oxidn.-sensitive nanoparticles have been decorated with an oxidizing enzyme (glucose oxidase) for release behavior that is responsive to the presence of the enzyme substrate (glucose). [on SciFinder (R)]