Responsive biomimetic networks from polyisocyanopeptide hydrogels.

Mechanical responsiveness is essential to all biological systems down to the level of tissues and cells. The intra- and extracellular mechanics of such systems are governed by a series of proteins, such as microtubules, actin, intermediate filaments and collagen. As a general design motif, these proteins self-assemble into helical structures and superstructures that differ in diameter and persistence length to cover the full mechanical spectrum. Gels of cytoskeletal proteins display particular mechanical responses (stress stiffening) that until now have been absent in synthetic polymeric and low-molar-mass gels. Here we present synthetic gels that mimic in nearly all aspects gels prepared from intermediate filaments. They are prepared from polyisocyanopeptides grafted with oligo(ethylene glycol) side chains. These responsive polymers possess a stiff and helical architecture, and show a tunable thermal transition where the chains bundle together to generate transparent gels at extremely low concentrations. Using characterization techniques operating at different length scales (for example, macroscopic rheology, atomic force microscopy and molecular force spectroscopy) combined with an appropriate theoretical network model, we establish the hierarchical relationship between the bulk mechanical properties and the single-molecule parameters. Our results show that to develop artificial cytoskeletal or extracellular matrix mimics, the essential design parameters are not only the molecular stiffness, but also the extent of bundling. In contrast to the peptidic materials, our polyisocyanide polymers are readily modified, giving a starting point for functional biomimetic hydrogels with potentially a wide variety of applications, in particular in the biomedical field.

301-nm wavelength tunable differentially driven all-polymer optical filter.

An optical filter based on all-polymer grating-assisted directional coupler is demonstrated. The wavelength tuning is differentially driven. The heater-electrodes created on the sidewalls of the polymer ridge can either blue- or red-shift the central wavelength. A total tuning range of 301 nm is achieved experimentally. The maximal local temperature gradient introduced across the coupler region is only 55°C-68°C. The filter is also insensitive to uniform ambient temperature change. Central wavelength jitter of ±3 nm is observed when the chip holder temperature cycles between 20°C and 80°C.

Beta sheets with a twist: the conformation of helical polyisocyanopeptides determined by using vibrational circular dichroism.

Detailed information on the architecture of polyisocyanopeptides based on vibrational circular dichroism (VCD) spectroscopy in combination with DFT calculations is presented. It is demonstrated that the screw sense of the helical polyisocyanides can be determined directly from the C=N-stretch vibrational region of the VCD spectrum. Analysis of the VCD signals associated with the amide I and amide II modes provides detailed information on the peptide side-chain arrangement in the polymer and indicates the presence of a helical ß-sheet architecture, in which the dihedral angles are slightly different to those of natural ß-sheet helices.

Carbazole functionalized isocyanide brushes in heterojunction photovoltaic devices.

In this work, carbazole-containing polyisocyanide (PIACz) brushes were used for photovoltaic devices. A photovoltaic device was fabricated on top of the brushes by spin-coating a suitable acceptor and evaporating an Al cathode. Devices with a poly(N-vinylcarbazole) (PVK) bulk polymer were also prepared for comparison. Interestingly, the brushes showed better photovoltaic characteristics as compared to the blended PVK system. This is attributed to the specific morphologies of the polyisocyanide brushes, which provide a large interfacial area between the donor and acceptor for efficient photogeneration. It was found that the device performance varied according to the molecular size of the incorporated acceptors.

Click and pick: identification of sialoside analogues for siglec-based cell targeting.

Click 'n' chips: Azide and alkyne-bearing sialic acids (purple diamond; see picture) were subjected to high-throughput click chemistry to generate a library of sialic acid analogues. Microarray printing of the library and screening with the siglec family of sialic-acid-binding proteins, led to the identification of high-affinity ligands for siglec-9 and siglec-10.

Hydrogen bonding and chemical shift assignments in carbazole functionalized isocyanides from solid-state NMR and first-principles calculations.

Carbazole functionalized polyisocyanides are known to exhibit excellent electronic properties (E. Schwartz, et al., Chemistry of Materials, 2010, 22, 2597). The functionalities and properties of such materials crucially depend on the organization and stability of the polymer structure. We combine solid-state Nuclear Magnetic Resonance (NMR) experiments with first-principles calculations of isotropic chemical shifts, within the recently developed converse approach, to rationalize the origin of isotropic chemical shifts in the crystalline monomer l-isocyanoalanine 2-(9H-carbazol-9-yl) ethyl amide (monomer 1) and thereby gain insight into the structural organization of its polymer (polymer 2). The use of state-of-the-art solid-state NMR experiments combined with Density Functional Theory (DFT) based calculations allows an unambiguous assignment of all proton and carbon resonances of the monomer. We were able to identify the structure stabilising interactions in the crystal and understand the influence of the molecular packing in the crystal structure on the chemical shift data observed in the NMR spectra. Here the Nuclear Independent Chemical Shift (NICS) approach allows discriminating between 'physical' interactions amongst neighboring molecules such as ring-current effects and 'chemical' interactions such as hydrogen bonding. This analysis reveals that the isocyanide monomer is stabilized by multiple hydrogen bonds such as a bifurcated hydrogen bond involving -N-H, -C-H and O=C- moieties and Ar-H···C≡N- hydrogen bonding (Ar = aromatic group). Based on the geometrical arrangement it is postulated that the carbazole units are involved in the weak σ-π interactions giving rise to a Herringbone packing of the molecules. The chemical shift analysis of the polymer spectra readily establishes the existence of N-H···O=C hydrogen bonds despite the limited resolution exhibited by the polymer spectra. It is also elucidated that the relative arrangement of the carbazole units in the polymer differs significantly from that of the monomer.

Macromolecular multi-chromophoric scaffolding.

This critical review describes recent efforts in the field of chromophoric scaffolding. The advances in this research area, with an emphasis on rigid scaffolds, for example, synthetic polymers, carbon nanotubes (CNTs), nucleic acids, and viruses, are presented (166 references).

Cysteine-containing polyisocyanides as versatile nanoplatforms for chromophoric and bioscaffolding.

The straightforward syntheses of polyisocyanides containing the alanine-cysteine motif in their side chains have been achieved. Detailed characterization of the polymers revealed a well-defined and highly stable helical conformation of the polyimine backbone responsible for the formation of rodlike structures of over one hundred nanometers. The 4(1) helix is further stabilized by beta-sheet-like interactions between the peptide arms. As a result, the cysteine sulfur atoms are regularly aligned along the polymer axis, which provides a unique platform for the scaffolding of various entities by using versatile click-chemistry postmodification approaches. For instance, pyrene derivatives were introduced through thio-specific reactions involving either maleimide, iodoacetamide, or thioester groups, leading to arrays of stacked chromophores with excimer-like emission. A water-soluble cysteine-rich polyisocyanide was successfully biotinylated and coupled to streptavidin.

The relationship between nanoscale architecture and charge transport in conjugated nanocrystals bridged by multichromophoric Polymers.

We report on the self-assembly and the electrical characterization of bicomponent films consisting of an organic semiconducting small molecule blended with a rigid polymeric scaffold functionalized in the side chains with monomeric units of the same molecule. The molecule and polymer are a perylene-bis(dicarboximide) monomer (M-PDI) and a perylene-bis(dicarboximide)-functionalized poly(isocyanopeptide) (P-PDI), which have been codeposited on SiO(x) and mica substrates from solution. These bicomponent films have been characterized by atomic force microscopy (AFM) and Kelvin probe force microscopy (KPFM), revealing the relationship between architecture and function for various supramolecular nanocrystalline arrangements at a nanometer spatial resolution. Monomer-polymer interactions can be controlled by varying solvent and/or substrate polarity, so that either the monomer packing dictates the polymer morphology or vice versa, leading to a morphology exhibiting M-PDI nanocrystals connected with each other by P-PDI polymer wires. Compared to pure M-PDI or P-PDI films, those bicomponent films that possess polymer interconnections between crystallites of the monomer display a significant improvement in electrical connectivity and a 2 orders of magnitude increase in charge carrier mobility within the film, as measured in thin film transistor (TFT) devices. Of a more fundamental interest, our technique allows the bridging of semiconducting crystals, without the formation of injection barriers at the connection points.

"Helter-skelter-like" perylene polyisocyanopeptides.

Exciton migration! Spectroscopic analyses and extensive molecular dynamics studies revealed a well-defined 4(1) helix in which the perylene molecules (see figure) form four "helter-skelter-like" overlapping pathways along which excitons and electrons can rapidly migrate.We report on a combined experimental and computational investigation on the synthesis and thorough characterization of the structure of perylene-functionalized polyisocyanides. Spectroscopic analyses and extensive molecular dynamics studies revealed a well defined 4(1) helix in which the perylene molecules form four "helter skelter-like" overlapping pathways along which excitons and electrons can rapidly migrate. The well-defined polymer scaffold stabilized by hydrogen bonding, to which the chromophores are attached, accounts for the precise architectural definition, and molecular stiffness observed for these molecules. Molecular-dynamics studies showed that the chirality present in these polymers is expressed in the formation of stable right-handed helices. The formation of chiral supramolecular structures is further supported by the measured and calculated bisignated Cotton effect. The structural definition of the chromophores aligned in one direction along the backbone is highlighted by the extremely efficient exciton migration rates and charge densities measured with Transient Absorption Spectroscopy.

Vibrational self-trapping in beta-sheet structures observed with femtosecond nonlinear infrared spectroscopy.

Self-trapping of NH-stretch vibrational excitations in synthetic beta-sheet helices is observed using femtosecond infrared pump-probe spectroscopy. In a dialanine-based beta-sheet helix, the transient-absorption change upon exciting the NH-stretch mode exhibits a negative absorption change at the fundamental frequency and two positive peaks at lower frequencies. These two induced-absorption peaks are characteristic for a state in which the vibrational excitation is self-trapped on essentially a single NH-group in the hydrogen-bonded NH...OC chain, forming a small (Holstein) vibrational polaron. By engineering the structure of the polymer we can disrupt the hydrogen-bonded NH...OC chain, allowing us to eliminate the self-trapping, as is confirmed from the NH-stretch pump-probe response. We also investigate a trialanine-based beta-sheet helix, where each side chain participates in two NH...OC chains with different hydrogen-bond lengths. The chain with short hydrogen bonds shows the same self-trapping behavior as the dialanine-based beta-sheet helix, whereas in the chain with long hydrogen bonds the self-trapping is too weak to be observable.

The relationship between nanoscale architecture and function in photovoltaic multichromophoric arrays as visualized by Kelvin probe force microscopy.

The physicochemical properties of organic (multi)component films for optoelectronic applications depend on both the mesoscopic and nanoscale architectures within the semiconducting material. Two main classes of semiconducting materials are commonly used: polymers and (liquid) crystals of small aromatic molecules. Whereas polymers (e.g., polyphenylenevinylenes and polythiophenes) are easy to process in solution in thin and uniform layers, small molecules can form highly defined (liquid) crystals featuring high charge mobilities. Herein, we combine the two material types by employing structurally well-defined polyisocyanopeptide polymers as scaffolds to precisely arrange thousands of electron-accepting molecules, namely, perylenebis(dicarboximides) (PDIs), in defined chromophoric wires with lengths of hundreds of nanometers. The polymer backbone enforces high control over the spatial location of PDI dyes, favoring both enhanced exciton and charge transfer. When blended with an electron-donor system such as regioregular poly(3-hexylthiophene), this polymeric PDI shows a relative improvement in charge generation and diffusion with respect to monomeric, aggregated PDI. In order to correlate this enhanced behavior with respect to the architecture, atomic force microscopy investigations on the mixtures were carried out. These studies revealed that the two polymers form interpenetrated bundles having a nanophase-segregated character and featuring a high density of contact points between the two different phases. In order to visualize the relationship between the architecture and the photovoltaic efficiency, Kelvin probe force microscopy measurements were carried out on submonolayer-thick films. This technique allowed for the first time the direct visualization of the photovoltaic activity occurring in such a nanoscale phase-segregated ultrathin film with true nanoscale spatial resolution, thus making possible a study of the correlation between function and architecture with nanoscale resolution.

Nanoscale Study of Polymer Dynamics.

The thermal motion of polymer chains in a crowded environment is anisotropic and highly confined. Whereas theoretical and experimental progress has been made, typically only indirect evidence of polymer dynamics is obtained either from scattering or mechanical response. Toward a complete understanding of the complicated polymer dynamics in crowded media such as biological cells, it is of great importance to unravel the role of heterogeneity and molecular individualism. In the present work, we investigate the dynamics of synthetic polymers and the tube-like motion of individual chains using time-resolved fluorescence microscopy. A single fluorescently labeled polymer molecule is observed in a sea of unlabeled polymers, giving access to not only the dynamics of the probe chain itself but also to that of the surrounding network. We demonstrate that it is possible to extract the characteristic time constants and length scales in one experiment, providing a detailed understanding of polymer dynamics at the single chain level. The quantitative agreement with bulk rheology measurements is promising for using local probes to study heterogeneity in complex, crowded systems.

Disubstituted Sialic Acid Ligands Targeting Siglecs CD33 and CD22 Associated with Myeloid Leukaemias and B Cell Lymphomas.

The siglec family of sialic acid-binding proteins are endocytic immune cell receptors that are recognized as potential targets for cell directed therapies. CD33 and CD22 are prototypical members and are validated candidates for targeting acute myeloid leukaemia and non-Hodgkin's lymphomas due to their restricted expression on myeloid cells and B-cells, respectively. While nanoparticles decorated with high affinity siglec ligands represent an attractive platform for delivery of therapeutic agents to these cells, a lack of ligands with suitable affinity and/or selectivity has hampered progress. Herein we describe selective ligands for both of these siglecs, which when displayed on liposomal nanoparticles, can efficiently target the cells expressing them in peripheral human blood. Key to their identification was the development of a facile method for chemo-enzymatic synthesis of disubstituted sialic acid analogues, combined with iterative rounds of synthesis and rapid functional analysis using glycan microarrays.

On-chip synthesis and screening of a sialoside library yields a high affinity ligand for Siglec-7.

The Siglec family of sialic acid-binding proteins are differentially expressed on white blood cells of the immune system and represent an attractive class of targets for cell-directed therapy. Nanoparticles decorated with high-affinity Siglec ligands show promise for delivering cargo to Siglec-bearing cells, but this approach has been limited by a lack of ligands with suitable affinity and selectivity. Building on previous work employing solution-phase sialoside library synthesis and subsequent microarray screening, we herein report a more streamlined 'on-chip' synthetic approach. By printing a small library of alkyne sialosides and subjecting these to 'on-chip' click reactions, the largest sialoside analogue library to date was generated. Siglec-screening identified a selective Siglec-7 ligand, which when displayed on liposomal nanoparticles, allows for targeting of Siglec-7(+) cells in peripheral human blood. In silico docking to the crystal structure of Siglec-7 provides a rationale for the affinity gains observed for this novel sialic acid analogue.

Sequential energy and electron transfer in polyisocyanopeptide-based multichromophoric arrays.

We report on the synthesis and detailed photo-physical investigation of four model chromophore side chain polyisocyanopeptides: two homopolymers of platinum-porphyrin functionalized polyisocyanopeptides (Pt-porphyrin-PIC) and perylene-bis(dicarboximide) functionalized polyisocyanopeptides (PDI-PIC), and two statistical copolymers with different ratios of Pt-porphyrin and PDI molecules attached to a rigid, helical polyisocyanopeptide backbone. (1)H NMR and circular dichroism measurements confirm that our model compounds retain a chiral architecture in the presence of the chromophores. The combination of Pt-porphyrin and PDI chromophores allows charge- and/or energy transfer to happen. We observe the excitation and relaxation pathways for selective excitation of the Pt-porphyrin and PDI chromophores. Studies of photoluminescence and transient absorption on nanosecond and picosecond scales upon excitation of Pt-porphyrin chromophores in our multichromophoric assemblies show similar photophysical features to those of the Pt-porphyrin monomers. In contrast, excitation of perylene chromophores results in a series of energy and charge transfer processes with the Pt-porphyrin group and forms additional charge-transfer states, which behave as an intermediate state that facilitates electronic coupling in these multichromophoric systems.

Macromolecular scaffolding: the relationship between nanoscale architecture and function in multichromophoric arrays for organic electronics.

The optimization of the electronic properties of molecular materials based on optically or electrically active organic building blocks requires a fine-tuning of their self-assembly properties at surfaces. Such a fine-tuning can be obtained on a scale up to 10 nm by mastering principles of supramolecular chemistry, i.e., by using suitably designed molecules interacting via pre-programmed noncovalent forces. The control and fine-tuning on a greater length scale is more difficult and challenging. This Research News highlights recent results we obtained on a new class of macromolecules that possess a very rigid backbone and side chains that point away from this backbone. Each side chain contains an organic semiconducting moiety, whose position and electronic interaction with neighboring moieties are dictated by the central macromolecular scaffold. A combined experimental and theoretical approach has made it possible to unravel the physical and chemical properties of this system across multiple length scales. The (opto)electronic properties of the new functional architectures have been explored by constructing prototypes of field-effect transistors and solar cells, thereby providing direct insight into the relationship between architecture and function.

Self-trapped vibrational states in synthetic beta-sheet helices.

Femtosecond vibrational pump-probe spectroscopy on beta-helical polyisocyanopeptides reveals vibrational self-trapping in the well-defined hydrogen-bonded side groups that is absent when non-hydrogen bonded monomers are mixed in.

X-ray spectroscopic and diffraction study of the structure of the active species in the Ni(II)-catalyzed polymerization of isocyanides.

The structure of the active complex in the Ni-catalyzed polymerization of isocyanides to give polyisocyanides is investigated. It is shown by X-ray absorption spectroscopy (XAS), including EXAFS (extended X-ray absorption fine structure) and XANES (X-ray absorption near edge structure), and single-crystal X-ray diffraction, to contain a carbene-like ligand. This is the first structural characterization of a crucial intermediate in the so-called merry-go-round mechanism for Ni-catalyzed isocyanide polymerization.