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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.

Helical structures play a vital role in nature, offering mechanical rigidity, chirality and structural definition to biological systems. Little is known about the influence of the helical architecture on the intrinsic properties of polymers. Here, we offer an insight into the nano architecture of helical polymers by measuring helical polyisocyanopeptides with single molecule force spectroscopy. An unprecedented large heterogeneity in the stiffness of the polymers was found. The heterogeneity persisted when the stiffness of these polymers was steered by: (1) enhancing the formation of the hydrogen bonding network along the polymer, (2) via pi-pi stacking interactions of aromatic perylenes, and (3) by changing the stereochemistry of the side chain. However, the heterogeneity was lost after completely disrupting the secondary structure by the addition of trifluoroacetic acid. Molecular dynamics simulations revealed three possible structural conformations which can account for the observed heterogeneity and their corresponding energy landscape is proposed.

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.

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.

Photovoltaic devices incorporating perylene-substituted polyisocyanide materials have been demonstrated, using blend systems with polythiophene- and polyfluorene-based conjugated polymers. Prototypical structures with nominal (1:1) blend weight ratios of the polyisocyanide with poly(3-hexylthiophene) (P3HT) and poly(9,9'-dioctylfluorene-co-bis(N,N'-(4-butylphenyl))-bis(N,N'- phenyl)-1,4-phenyldiamine) (PFB) readily showed an order of magnitude improvement in power conversion efficiency, as compared to analogous blend architectures using a perylene (PDI) monomer, whereas the performance of strongly phase-separated F8BT (poly(9,9- dioctylfluorene-co-benzothidiazole) blend devices showed no such improvement. We propose that the use of polyisocyanide chains as a molecular template offers a method by which the morphology and connectivity of photovoltaic blends can be modified and enhanced. © 2009 American Chemical Society.

The electronic transport properties of stacks of perylene-bis(dicarboximide) (PDI) chromophores, covalently fixed to the side arms of rigid, helical polyisocyanopeptides, are studied using thin-film transistors. In device architectures where the transistor channel lengths are somewhat greater than the average polymer chain length, carrier mobilities of order 10−3 cm2 V−1 s−1 at 350 K are found, which are limited by inter-chain transport processes. The influence of π–π interactions on the material properties is studied by using PDIs with and without bulky substituents in the bay area. In order to attain a deeper understanding of both the electronic and the electronic-transport properties of these systems, studies of self-assembly on surfaces are combined with electronic characterization using Kelvin probe force microscopy, and also a theoretical study of electronic coupling. The use of a rigid polymer backbone as a scaffold to achieve a full control over the position and orientation of functional groups is of general applicability and interest in the design of building blocks for technologically important functional materials, as well as in more fundamental studies of chromophoric interactions.

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.

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.

This contribution describes the synthesis and full characterization of oligo(ethylene glycol) functionalized polyisocyanopeptides. The thermal behavior of the resulting semi-flexible polymers was investigated in diluted aqueous conditions and features a tunable Lower Critical Solution Temperature (LCST). In line with previously described oligo(ethylene glycol) decorated polymers, the LCST of the materials shows a very small hysteresis effect and directly correlates with the oligo(ethylene glycol) side-chains length; short oligo(ethylene glycol) substituents are associated with lower LCST. In contrast with poly[oligo(ethylene glycol) methacrylate], a significant effect of the degree of polymerization (DP) of the poly(isocyanopeptide) core on the LSCT of the materials was observed. Most remarkably, poly(isocyanopeptide)-graft-oligo(ethylene glycol) chains of high DP lead to the reversible formation of strong hydrogels above the transition temperature, even at very low polymer concentration (0.1 wt.%). AFM studies point towards the formation of a highly organized fibrillar network in the gel-state, reminiscent of structures observed for low molecular weight gelators, polysaccharides, and protein-based (hydro)gels. It is proposed that the stiff and well-defined helical poly(isocyanopeptide) backbone avoids the collapse of the chains into globules at the transition temperature as usually observed for more flexible systems. Thus, above a critical DP the semi-flexible non-linear PEGs chains are getting kinetically trapped in an extended fibrillar network, when the oligo(ethylene glycol) corona hydrophilicity is lowered at higher temperature. As a result these polymers exhibit a strong ability to gel water at extremely low polymer concentrations.

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.

Rigid rod polyisocyanopeptides bearing phthalocyanines as pendant groups have been synthesised through CuAAC of polyisocyanopeptides containing acetylene groups with zinc(II) phthalocyanine azide. As confirmed by UV/Vis, fluorescence, and circular dichroism spectroscopies, the phthalocyanines are arranged in a helical fashion along the polymer backbone, forming the longest reported well-defined phthalocyanine assembly described to date.

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.

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 supra molecular 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-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 center dot center dot center dot OC chain, forming a small (Holstein) vibrational polaron. By engineering the structure of the polymer we can disrupt the hydrogen-bonded NH center dot center dot center dot 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 center dot center dot center dot 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.

This article describes the first surface-initiated polymerization of isocyanide monomers onto various surfaces in a controlled manner. Brushes up to 200 nm could be easily obtained within 3 h of polymerization, and the polymer growth was studied as a function of reaction time, monomer concentration, and growth conditions, using atomic force microscopy (AFM) and ellipsometry. The monomers used in this study contain dipeptide (L,L-Ala-Ala) side groups; circular dichroism (CD) measurements, Fourier transform infrared spectroscopy (FTIR), and AFM confirmed that the well-defined helical conformation was retained in the polyisocyanide brushes with hydrogen bonds along the polymer chains.

Contains fulltext : 36705.pdf (Author’s version postprint ) (Open Access) The structure of the active complex in the Ni-cotolyzed polymerization of isocyonides 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-coiled merry-go-round mechanism for Ni-catolyzed isocyanide polymerization.

Solidification controlled by vacancy diffusion is studied by Monte Carlo simulations of a two-dimensional Ising model defined by a Hamiltonian which models a thermally driven fluid-solid phase transition. The nonequilibrium morphology of the growing solid is studied as a function of time as the system relaxes into equilibrium described by a temperature. At low temperatures the model exhibits fractal growth at early times and crossover to compact solidification as equilibrium is approached.

A simple two-dimensional microscopic model is proposed to describe solidifcation processes in systems with impurities which are miscible only in the fluid phase. Computer simulation of the model shows that the resulting solids are fractal over a wide range of impurity concentrations and impurity diffusional constants. A fractal-forming mechanism is suggested for impurity-controlled solidification which is consistent with recent experimental observations of fractal growth of solid phospholipid domains in monolayers. The Journal of Chemical Physics is copyrighted by The American Institute of Physics.