Pol Besenius

Single-chain folding of polymers for catalytic systems in water

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.

Supramolecular Polymers in Aqueous Media

This review discusses one-dimensional supramolecular polymers that form in aqueous media. First, naturally occurring supramolecular polymers are described, in particular, amyloid fibrils, actin filaments, and microtubules. Their structural, thermodynamic, kinetic, and nanomechanical properties are highlighted, as well as their importance for the advancement of biologically inspired supramolecular polymer materials. Second, five classes of synthetic supramolecular polymers are described: systems based on (1) hydrogen-bond motifs, (2) large π-conjugated surfaces, (3) host-guest interactions, (4) peptides, and (5) DNA. We focus on recent studies that address key challenges in the field, providing mechanistic understanding, rational polymer design, important functionality, robustness, or unusual thermodynamic and kinetic properties.

Controlling the Growth and Shape of Chiral Supramolecular Polymers in Water

A challenging target in the noncovalent synthesis of nanostructured functional materials is the formation of uniform features that exhibit well-defined properties, e.g., precise control over the aggregate shape, size, and stability. In particular, for aqueous-based one-dimensional supramolecular polymers, this is a daunting task. Here we disclose a strategy based on self-assembling discotic amphiphiles that leads to the control over stack length and shape of ordered, chiral columnar aggregates. By balancing out attractive noncovalent forces within the hydrophobic core of the polymerizing building blocks with electrostatic repulsive interactions on the hydrophilic rim we managed to switch from elongated, rod-like assemblies to small and discrete objects. Intriguingly this rod-to-sphere transition is expressed in a loss of cooperativity in the temperature-dependent self-assembly mechanism. The aggregates were characterized using circular dichroism, UV and 1H-NMR spectroscopy, small angle X-ray scattering, and cryotransmission electron microscopy. In analogy to many systems found in biology, mechanistic details of the self-assembly pathways emphasize the importance of cooperativity as a key feature that dictates the physical properties of the produced supramolecular polymers.

Dynamic combinatorial discovery of a [2]-catenane and its guest-induced conversion into a molecular square host

A simple water-soluble naphthalenedithiol building block is converted quantitatively into a series of octameric [2]-catenanes, composed of two interlocked molecular squares. When this mixture is re-equilibrated in the presence of an adamantyl ammonium guest, the catenanes disassemble into their macrocyclic components that bind the guest with nanomolar affinity in water.

pH-Switchable ampholytic supramolecular copolymers.

β-sheet-encoded anionic and cationic dendritic peptide amphiphiles form supramolecular copolymers when self-assembled in a 1:1 feed ratio of the monomers. These ampholytic materials have been designed for on-off polymerization in response to pH triggers. The cooperative supramolecular self-assembly process is switched on at a physiologically relevant pH value and can be switched off by increasing or decreasing the pH value.

Paramagnetic self-assembled nanoparticles as supramolecular MRI contrast agents

Nanometer-sized materials offer a wide range of applications in biomedical technologies, particularly imaging and diagnostics. Current scaffolds in the nanometer range predominantly make use of inorganic particles, organic polymers or natural peptide-based macromolecules. In contrast we hereby report a supramolecular approach for the preparation of self-assembled dendritic-like nanoparticles for applications as MRI contrast agents. This strategy combines the benefits from low molecular weight imaging agents with the ones of high molecular weight. Their in vitro properties are confirmed by in vivo measurements: post injection of well-defined and meta-stable nanoparticles allows for high-resolution blood-pool imaging, even at very low Gd(III) doses. These dynamic and modular imaging agents are an important addition to the young field of supramolecular medicine using well-defined nanometer-sized assemblies.

Controlled Supramolecular Oligomerization of C3‐Symmetrical Molecules in Water: The Impact of Hydrophobic Shielding

The supramolecular oligomerization of three water-soluble C(3)-symmetrical discotic molecules is reported. The compounds all possess benzene-1,3,5-tricarboxamide cores and peripheral Gd(III)-DTPA (diethylene triamine pentaacetic acid) moieties, but differ in their linker units and thus in their propensity to undergo secondary interactions in H(2)O. The self-assembly behavior of these molecules was studied in solution using circular dichroism, UV/Vis spectroscopy, nuclear magnetic resonance, and cryogenic transmission electron microscopy. The aggregation concentration of these molecules depends on the number of secondary interactions and on the solvophobic character of the polymerizing moieties. Hydrophobic shielding of the hydrogen-bonding motif in the core of the discotic is of paramount importance for yielding stable, helical aggregates that are designed to be restricted in size through anti-cooperative, electrostatic, repulsive interactions.

Side chains control dynamics and self-sorting in fluorescent organic nanoparticles

To develop fluorescent organic nanoparticles with tailored properties for imaging and sensing, full control over the size, fluorescence, stability, dynamics, and supramolecular organization of these particles is crucial. We have designed, synthesized, and fully characterized 12 nonionic fluorene co-oligomers that formed self-assembled fluorescent nanoparticles in water. In these series of molecules, the ratio of hydrophilic ethylene glycol and hydrophobic alkyl side chains was systematically altered to investigate its role on the above-mentioned properties. The nanoparticles consisting of π-conjugated oligomers containing polar ethylene glycol side chains were less stable and larger in size, while nanoparticles self-assembled from oligomers containing nonpolar pendant chains were more stable, smaller, and generally had a higher fluorescence quantum yield. Furthermore, the dynamics of the molecules between the nanoparticles was enhanced if the number of hydrophilic side chains increased. Energy transfer studies between naphthalene and benzothiadiazole fluorene co-oligomers with the same side chains showed no exchange of molecules between the particles for the apolar molecules. For the more polar systems, the exchange of molecules between nanoparticles took place at room temperature or after annealing. Self-assembled nanoparticles consisting of π-conjugated oligomers having different side chains caused self-sorting, resulting either in the formation of domains within particles or the formation of separate nanoparticles. Our results show that we can control the stability, fluorescence, dynamics, and self-sorting properties of the nanoparticles by simply changing the nature of the side chains of the π-conjugated oligomers. These findings are not only important for the field of self-assembled nanoparticles but also for the construction of well-defined multicomponent supramolecular materials in general.

pH-switchable self-assembled materials.

Self-assembled materials, which are able to respond to external stimuli, have been extensively studied over the last decades. A particularly exciting stimulus for a wide range of biomedical applications is the pH value of aqueous solutions, since deprotonation-protonation events are crucial for structural and functional properties of biopolymers. In living cells and tissues, intra- and extracellular pH values are stringently regulated, but can deviate from pH neutral as observed for example in tumorous, inflammatory sites, in endocytic pathways, and specific cellular compartments. By using a pH-switch as a stimulus, it is thereby possible to address specific targets in order to cause a programmed response of the supramolecular material. This strategy has not only been successfully applied in fundamental research but also in clinical studies. In this feature article, current strategies that have been used in order to design materials with pH-responsive properties are illustrated. This discussion only addresses selected examples from the last four years, the self-assembly of polymer-based building blocks, assemblies emerging from small molecules including surfactants or derived from biological macromolecules, and finally the controlled self-assembly of oligopeptides.

Self-sorting in rodlike micelles of chiral bisurea bolaamphiphiles.

We have demonstrated the formation of segregated enantiomeric dynamic rods in water, from the self-sorting of chiral trans-1,2-bisureido cyclohexane-based bolaamphiphiles. Fluorescence probes have been used to investigate the self-sorting through forming exciplex and FRET.