Stereocontrolled, multi-functional sequence-defined oligomers through automated synthesis

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 occursviaring-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

Introducing Hyaluronic Acid into Supramolecular Polymers and Hydrogels

[Abstract] The use of supramolecular polymers to construct functional biomaterials is gaining more attention due to the tunable dynamic behavior and fibrous structures of supramolecular polymers, which resemble those found in natural systems, such as the extracellular matrix. Nevertheless, to obtain a biomaterial capable of mimicking native systems, complex biomolecules should be incorporated, as they allow one to achieve essential biological processes. In this study, supramolecular polymers based on water-soluble benzene-1,3,5-tricarboxamides (BTAs) were assembled in the presence of hyaluronic acid (HA) both in solution and hydrogel states. The coassembly of BTAs bearing tetra(ethylene glycol) at the periphery (BTA-OEG4) and HA at different ratios showed strong interactions between the two components that led to the formation of short fibers and heterogeneous hydrogels. BTAs were further covalently linked to HA (HA-BTA), resulting in a polymer that was unable to assemble into fibers or form hydrogels due to the high hydrophilicity of HA. However, coassembly of HA-BTA with BTA-OEG4 resulted in the formation of long fibers, similar to those formed by BTA-OEG4 alone, and hydrogels were produced with tunable stiffness ranging from 250 to 700 Pa, which is 10-fold higher than that of hydrogels assembled with only BTA-OEG4. Further coassembly of BTA-OEG4 fibers with other polysaccharides showed that except for dextran, all polysaccharides studied interacted with BTA-OEG4 fibers. The possibility of incorporating polysaccharides into BTA-based materials paves the way for the creation of dynamic complex biomaterials.The authors acknowledge the ICMS Animation Studio for providing the artwork. S.V.-A. and G.M. acknowledge the funding received by Gravitation Program “Materials Driven Regeneration,” funded by the Netherlands Organization for Scientific Research (024.003.013). J.M. acknowledges a Marie Skłodowska-Curie postdoctoral fellowship (794016) for financial support. G.M. acknowledges the funding received by the Swiss National Science Foundation (SNSF “Early PostDoc Mobility” P2EZP2-178435). R.C. acknowledges TA Instruments for providing the DHR-3 rheometer under the Young Distinguished Rheologist Award instrument grant. S.S. and E.W.M acknowledge the European Research Council (H2020-EU.1.1., SYNMAT project, ID 788618).Netherlands Organisation for Scientific Research; 024.003.013Swiss National Science Foundation; P2EZP2-17843

Helicity Control in the Aggregation of Achiral Squaraine Dyes in Solution and Thin Films

Squaraine dyes are well known for their strong absorption in the visible regime. Reports on chiral squaraine dyes are, however, scarce. To address this gap, we here report two novel chiral squaraine dyes and their achiral counterparts. The presented dyes are aggregated in solution and in thin films. A detailed chiroptical study shows that thin films formed by co-assembling the chiral dye with its achiral counterpart exhibit exceptional photophysical properties. The circular dichroism (CD) of the co-assembled structures reaches a maximum when just 25 % of the chiral dye are present in the mixture. The solid structures with the highest relative CD effect are achieved when the chiral dye is used solely as a director, rather than the structural component. The chiroptical data are further supported by selected spin-filtering measurements using mc-AFM. These findings provide a promising platform for investigating the relationship between the dissymmetry of a supramolecular structure and emerging material properties rather than a comparison between a chiral molecular structure and an achiral counterpart

Control of Electrons' Spin Eliminates Hydrogen Peroxide Formation during Water Splitting

The production of hydrogen through water splitting in a photoelectrochemical cell suffers from an overpotential that limits the efficiencies. In addition, hydrogen-peroxide formation is identified as a competing process affecting the oxidative stability of photoelectrodes. We impose spin-selectivity by coating the anode with chiral organic semiconductors from helically aggregated dyes as sensitizers; Zn-porphyrins and triarylamines. Hydrogen peroxide formation is dramatically suppressed, while the overall current through the cell, correlating with the water splitting process, is enhanced. Evidence for a strong spin-selection in the chiral semiconductors is presented by magnetic conducting (mc-)AFM measurements, in which chiral and achiral Zn-porphyrins are compared. These findings contribute to our understanding of the underlying mechanism of spin selectivity in multiple electron-transfer reactions and pave the way toward better chiral dye-sensitized photoelectrochemical cells

Effect of H-Bonding on Order Amplification in the Growth of a Supramolecular Polymer in Water

While a great deal of knowledge on the roles of hydrogen bonding and hydrophobicity in proteins has resulted in the creation of rationally designed and functional peptidic structures, the roles of these forces on purely synthetic supramolecular architectures in water have proven difficult to ascertain. Focusing on a 1,3,5-benzenetricarboxamide (BTA)-based supramolecular polymer, we have designed a molecular modeling strategy to dissect the energetic contributions involved in the self-assembly (electrostatic, hydrophobic, etc.) upon growth of both ordered BTA stacks and random BTA aggregates. Utilizing this set of simulations, we have unraveled the cooperative mechanism for polymer growth, where a critical size must be reached in the aggregates before emergence and amplification of order into the experimentally observed fibers. Furthermore, we have found that the formation of ordered fibers is favored over disordered aggregates solely on the basis of electrostatic interactions. Detailed analysis of the simulation data suggests that H-bonding is a major source of this stabilization energy. Experimental and computational comparison with a newly synthesized 1,3,5-benzenetricarboxyester (BTE) derivative, lacking the ability to form the H-bonding network, demonstrated that this BTE variant is also capable of fiber formation, albeit at a reduced persistence length. This work provides unambiguous evidence for the key 1D driving force of hydrogen bonding in enhancing the persistency of monomer stacking and amplifying the level of order into the growing supramolecular polymer in water. Our computational approach provides an important relationship directly linking the structure of the monomer to the structure and properties of the supramolecular polymer

Supramolecular copolymers: structure and composition revealed by theoretical modeling

Supramolecular copolymers, non-covalent analogues of synthetic copolymers, constitute a new and promising class of polymers. In contrast to their covalent counterparts, the details of their mechanism of formation, as well as the factors determining their composition and length, are still poorly understood. Here, the supramolecular copolymerization between two slightly structurally different benzene-1,3,5-tricarboxamide (BTA) monomers functionalized with either oligodimethylsiloxane (oDMSi) or alkyl side chains is unraveled by combining experimental and theoretical approaches. By applying the “sergeant-and-soldiers” approach using circular dichroism (CD) experiments, we are able to obtain detailed insights into the structure and composition of these supramolecular copolymers. Moreover, we observe an unexpected chiral induction upon mixing two independently CD-silent solutions of the achiral (soldier) and chiral (sergeant) monomers. We find that the subtle differences in the chemical structure of the two monomers impact their homopolymerization mechanism: whereas alkyl-BTAs cooperatively self-assemble, oDMSi-BTAs self-assemble in an isodesmic manner. The effect of these mechanistic differences in the supramolecular copolymerization process is investigated as a function of the composition of the two monomers and explicitly rationalized by mathematical modeling. The results show that, at low fractions of oDMSi-BTA sergeants (25 mol%), the isodesmic assembly of the increasing amounts of sergeant becomes more dominant, and different species start to coexist in the copolymerization process. The analysis of the experimental data with a newly developed theoretical model allows us to quantify the thermodynamic parameters, the distribution of different species, and the compositions and stack lengths of the formed supramolecular copolymers existing at various feed ratios of the two monomers.This work was financially supported by The Netherlands Organization for Scientific Research (NWO-TOP PUNT Grant 10018944) and the Dutch Ministry of Education, Culture and Science (Gravity Program 024.001.035)

Insights into the Kinetics of Supramolecular Comonomer Incorporation in Water

Multicomponent supramolecular polymers are a versatile platform to prepare functional architectures, but a few studies have been devoted to investigate their noncovalent synthesis. Here, we study supramolecular copolymerizations by examining the mechanism and time scales associated with the incorporation of new monomers in benzene-1,3,5-tricarboxamide (BTA)-based supramolecular polymers. The BTA molecules in this study all contain three tetra(ethylene glycol) chains at the periphery for water solubility but differ in their alkyl chains that feature either 10, 12 or 13 methylene units. C(10)BTA does not form ordered supramolecular assemblies, whereas C(12)BTA and C(13)BTA both form high aspect ratio supramolecular polymers. First, we illustrate that C(10)BTA can mix into the supramolecular polymers based on either C(12)BTA or C(13)BTA by comparing the temperature response of the equilibrated mixtures to the temperature response of the individual components in water. Subsequently, we mix C(10)BTA with the polymers and follow the copolymerization over time with UV spectroscopy and hydrogen/deuterium exchange mass spectrometry experiments. Interestingly, the time scales obtained in both experiments reveal significant differences in the rates of copolymerization. Coarse-grained simulations are used to study the incorporation pathway and kinetics of the C(10)BTA monomers into the different polymers. The results demonstrate that the kinetic stability of the host supramolecular polymer controls the rate at which new monomers can enter the existing supramolecular polymers

Polymorphism in the Assembly of Phase-Segregated Block Molecules: Pathway Control to 1D and 2D Nanostructures

Nanomaterials with highly ordered, one- or two-dimensional molecular morphologies have promising properties for adaptive materials. Here, we present the synthesis and structural characterization of dinitrohydrazone (hydz) functionalized oligodimethylsiloxanes (oDMSs) of discrete length, which form both 1- and 2D nanostructures by precisely controlling composition and temperature. The morphologies are highly ordered due to the discrete nature of the siloxane oligomers. Columnar, 1D structures are formed from the melt within a few seconds as a result of phase segregation in combination with π-π stacking of the hydrazones. By tuning the length of the siloxane, the synergy between these interactions is observed which results in a highly temperature sensitive material. Macroscopically, this gives a material that switches reversibly and fast between an ordered, solid and a disordered, liquid state at almost equal temperatures. Ordered, 2D lamellar structures are formed under thermodynamic control by cold crystallization of the hydrazones in the amorphous siloxane bulk via a slow process. We elucidate the 1- and 2D morphologies from the nanometer to molecular level by the combined use of solid state NMR and X-ray scattering. The exact packing of the hydrazone rods within the cylinders and lamellae surrounded the liquid-like siloxane matrix is clarified. These results demonstrate that controlling the assembly pathway in the bulk and with that, tuning the nanostructure dimensions and domain spacings, material properties are altered for applications in nanotechnology or thermoresponsive materials

Regional differences in the pattern of airway remodeling following chronic allergen exposure in mice

BACKGROUND: Airway remodeling present in the large airways in asthma or asthma models has been associated with airway dysfunction in humans and mice. It is not clear if airways distal to the large conducting airways have similar degrees of airway remodeling following chronic allergen exposure in mice. Our objective was to test the hypothesis that airway remodeling is heterogeneous by optimizing a morphometric technique for distal airways and applying this to mice following chronic exposure to allergen or saline. METHODS: In this study, BALB/c mice were chronically exposed to intranasal allergen or saline. Lung sections were stained for smooth muscle, collagen, and fibronectin content. Airway morphometric analysis of small (0–50000 μm(2)), medium (50000 μm(2)–175000 μm(2)) and large (>175000 μm(2)) airways was based on quantifying the area of positive stain in several defined sub-epithelial regions of interest. Optimization of this technique was based on calculating sample sizes required to detect differences between allergen and saline exposed animals. RESULTS: Following chronic allergen exposure BALB/c mice demonstrate sustained airway hyperresponsiveness. BALB/c mice demonstrate an allergen-induced increase in smooth muscle content throughout all generations of airways, whereas changes in subepithelial collagen and fibronectin content are absent from distal airways. CONCLUSION: We demonstrate for the first time, a systematic objective analysis of allergen induced airway remodeling throughout the tracheobronchial tree in mice. Following chronic allergen exposure, at the time of sustained airway dysfunction, BALB/c mice demonstrate regional differences in the pattern of remodeling. Therefore results obtained from limited regions of lung should not be considered representative of the entire airway tree