Intramolecular Cross-linking Research Articles

Molecular Dynamics Study on Behavior of Resist Molecules in UV-Nanoimprint Lithography Filling Process.

In this study, we performed molecular dynamics (MD) simulations of the filling process of few-nanometer-wide trenches with various resist materials in ultraviolet nanoimprint lithography (UV-NIL) to identify the main molecular features necessary for a successful filling process. The 2- and 3-nm wide trenches were successfully filled with the resist materials that had (experimentally determined) viscosities less than 10 mPa·s. The resist composed of a three-armed bulky and highly viscous molecule could not fill the trenches. The radius of gyration of this molecule was smaller than half of the distance in which the first peak of its radial distribution function occurred. The available shapes of 1,6-hexanediol diacrylate (HDDA) and tri(propylene glycol) diacrylate (TPGDA), which are linear photopolymers, were compared to reveal that TPGDA is more flexible and adopts more conformations than HDDA. The terminal functional groups of TPGDA can be close due to its flexibility, which would increase the probability of intramolecular crosslinking of the molecule. This simulation result could explain the difference in hardness between the UV-cured HDDA and TPGDA based materials observed by experiments. The findings revealed by our MD simulations provide useful information for selecting and designing resists for fine patterning by UV-NIL.

En Route to Stabilized Compact Conformations of Single-Chain Polymeric Nanoparticles in Complex Media.

Precise control over the folding pathways of polypeptides using a combination of noncovalent and covalent interactions has evolved into a wide range of functional proteins with a perfectly defined 3D conformation. Inspired hereby, we develop a series of amphiphilic copolymers designed to form compact, stable, and structured single-chain polymeric nanoparticles (SCPNs) of defined size, even in competitive conditions. The SCPNs are formed through a combination of noncovalent interactions (hydrophobic and hydrogen-bonding interactions) and covalent intramolecular cross-linking using a light-induced [2 + 2] cycloaddition. By comparing different self-assembly pathways of the nanoparticles, we show that, like for proteins in nature, the order of events matters. When covalent cross-links are formed prior to the folding via hydrophobic and supramolecular interactions, larger particles with less structured interiors are formed. In contrast, when the copolymers first fold via hydrophobic and hydrogen-bonding interactions into compact conformations, followed by covalent cross-links, good control over the size of the SCPNs and microstructure of the hydrophobic interior is achieved. Such a structured SCPN can stabilize the solvatochromic dye benzene-1,3,5-tricarboxamide–Nile Red via molecular recognition for short periods of time in complex media, while showing slow exchange dynamics with the surrounding complex media at longer time scales. The SCPNs show good biocompatibility with cells and can carry cargo into the lysosomal compartments of the cells. Our study highlights the importance of control over the folding pathway in the design of stable SCPNs, which is an important step forward in their application as noncovalent drug or catalyst carriers in biological settings.

Transglutaminase modified type A gelatin gel: The influence of intra-molecular and inter-molecular cross-linking on structure-properties

In this work, the structure–property differences and mechanisms of gelatin induced by transglutaminase (TGase) covalent cross-linking were investigated. The results showed that higher hardness was obtained with a cross-linking degree of 13.55%, attributing to an active intra-molecular cross-linking and a tight network structure under a certain amount of triple helix-like structure. The inter-molecular cross-linking played a positive role in the transition from random coil to left-handed single helix chains, while triple helix-like structure could not been formed owing to the steric hindrance and hydrogen bond reduction, showing the decrease of hardness and increase of viscosity. Additionally, the ε-(γ-Glu)-Lys isopeptide bond significantly increased the initial degradation temperature. Macromolecular polymers with a cross-linking degree of 37.48% allowed sol state of gelatin gel could be maintained even heating at 100 ℃ for 10 min. This study might provide an innovative reference for the regulation and application of gelatin gel structure-properties.

Dimensions of Network Polymers

AbstractThe mean‐square radius of gyration Rg2 and the graph diameter D of the network polymers formed through the random crosslinking of predetermined primary chains with a fixed number of intermolecular and intramolecular crosslinks are investigated by the numerical calculation based on the graph theory. In the case of ring‐free polymers, D is the longest end‐to‐end path length, sometimes referred to as the maximum span length. The expected Rg2‐value for a given D is found to follow a linear relationship, Rg2 = a D + b, similarly as in the cases of the ring‐free polymers. The proportional coefficient, a decreases approximately linearly with the number of intramolecular crosslinks kc, or the cycle rank in the graph theory, essentially independent of the total number k of crosslinks and the primary chain length distribution. The contraction factor g of the average Rg2 of the whole network polymer system is also governed by kc, and decreases with kc. One may be able to design and control the Rg2‐values of crosslinked polymers through the magnitude of D, which is usually easier to imagine than the complex 3D architecture.

Chiral Gold Clusters with Crosslinking Ligands: Geometric Structures and Chiroptical Activities

AbstractThe geometric diversity of ligand‐protected metal clusters has greatly provoked the interest in the chirality of gold clusters bearing crosslinking ligands, which are a subject of active investigations. This review introduces recent geometric and computational studies on chiral gold clusters whose metal core is covered by intramolecular crosslinking moieties. Following an overview of the structural constructions, the geometric features of the ligand shells and metal cores of chiral gold clusters are elucidated, where an emphasis is placed on the importance of helical patterns of the crosslinking ligands arranged around the gold cores. In addition, insights into the atomic‐level origin of chiroptical activity, which cannot be accessed solely through experiments, are presented from computational studies using numerical and theoretical approaches, thereby providing a novel methodology based on transition‐moment and transition‐density analyses.

Synthesis of waterborne polyurethane by inserting polydimethylsiloxane and constructing dual crosslinking for obtaining the superior performance of waterborne coatings

Polydimethylsiloxane (PDMS) is usually used to obtain favorable performances of waterborne polyurethane (WPU) such as higher hardness, exceptional thermal stability and lower interfacial tension. However, there is always a problem that waterborne polyurethane (WPU) often performs weak tensile strength, lower tenacity and brittle property at room temperature when polydimethylsiloxane (PDMS) is embedded into the backbone of polyurethane. The study aims to address the problem by constructing dual crosslinking structure, namely introducing trimethylolpropane as an intramolecular crosslinking agent into prepolymers and then adding waterborne polycarbodiimide (SK-400) as a post-crosslinking agent in order to further enlarge the degree of crosslinking and mainly make up for the shortcoming that mechanical property decreases when polydimethylsiloxane (PDMS) was inserted into molecule chains. Initially a novel inner-crosslinking prepolymer (SiWPU) comprising polydimethylsiloxane need to be synthesized successfully by inserting trimethylolpropane into prepolymers. Then the sample SiWPU-3 was picked out as a matrix resin and dropwise added polycarbodiimide (SK-400) as a post-crosslinking agent into the matrix resin (C–SiWPU). As pH was gradually lowering following the evaporation of triethylamine in the emulsion (C–SiWPU), carboxyl groups (COOH) in prepolymers started to react with SK-400 (NCN) to form twofold crosslinking structure. When 0%, 2%, 4%, 6%, and 8 wt% of waterborne polycarbodiimide (SK-400) was incorporated into the solution, the tensile strengths are 47.8 MPa, 57.7 MPa, 65 MPa, 57.6 MPa and 54.5 MPa and the elongation at break 732%, 756%, 798%, 707% and 700%. The crosslinking density of SiWPU-3 without the addition of waterborne polycarbodiimide (SK-400) is 3.86 × 10−3 mol/cm3. As 6 wt% of waterborne polycarbodiimide (SK-400) was added into the emulsion of SiWPU-3, the crosslinking density of C–SiWPU-6 (6 wt% SK-400) is 6.19 × 10−3 mol/cm3. The films show excellent extensibility and exceptional tenacity. Hence, the emulsion is able to be applied in leather industry.

Improvement of Thermal Stability of Amphipathic Peptide-Phospholipid Nanodiscs via Lateral Association of α-Helices by Disulfide Cross-Linking.

Amphipathic α-helical peptides have been reported to form discoidal particles or nanodiscs with phospholipids, in which a lipid bilayer patch is encircled by peptides. Peptide-based nanodiscs have broad applicability because of their ease of preparation, size flexibility, and structural plasticity. We previously revealed that the nanodiscs formed by apolipoprotein-A-I-derived peptide 18A showed temperature-dependent structural destabilization above the gel-to-liquid-crystalline phase transition temperature of the lipid bilayer. It has been suggested that this destabilization is due to the migration of peptides bound to the edge of the discs to the bilayer surface. In this study, we designed a peptide that could stabilize nanodisc structures against the phase transition of lipid bilayers by disulfide cross-linking of peptides. An 18A-dimer cross-linked by a proline residue, 37pA (Ac-18A-P-18A-CONH2), also showed thermal destabilization of nanodiscs like 18A. However, cross-linking the sides of the two α-helices of the cysteine-substituted analogue 37pA-C2 with disulfide bonds led to the formation of nanodiscs that were more stable to temperature changes. This stabilizing effect was mainly due to the formation of a cyclic 37pA-C2 monomer by intramolecular disulfide cross-linking. These results suggest that the lateral association of two α-helices, which is the basis of the double-belt structure, is an important factor for the implementation of stable nanodiscs. The results of this study will help in development of more stable nanoparticles with membrane proteins in the future.

Investigation on the Mechanism and Properties of a Novel Colloidal Dispersion Gel for Profile Modification in High Salinity Reservoir

Abstract A novel colloidal dispersion gel (CDG) was synthesized by cross-linking polysaccharide-based hyperbranched polymer (SMHBP) with aluminum citrate. Four factors affecting gelation properties were investigated including SMHBP concentration, the weight ratio of polymer to cross-linker, NaCl concentration, and additive concentration. Environmental scanning electron microscope (ESEM) was used to observe the morphologies of the CDG to understand the cross-linked mechanism. The CDG is cross-linked by both intramolecular and intermolecular, and the formation of the CDG is dominated by the intramolecular cross-linking reaction. Core displacement experiments demonstrated that the novel CDG obtained excellent profile modification performances at a high temperature and high salinity.

Synthesis of poly(N-vinyl pyrrolidone) (PVP) nanogels by gamma irradiation using different saturation atmospheres

Nanogels are internally crosslinked particles of nanometric size used in various fields e.g. as such as carriers in drug delivery systems. They can be produced using ionizing radiation in dilute aqueous solutions. This method is carried out in a pure polymer-solvent system, avoiding the addition of any additives such as monomers, surfactants, catalysts and crosslinking agents and no further purification step is necessary. Poly(N-vinyl pyrrolidone) (PVP K-90) nanogels were prepared by gamma irradiation in an aqueous solution. The samples were prepared in triplicate in multipurpose cobalt-60 gamma irradiator using 1, 10, 25 and 100 mM PVP solutions. Samples were irradiated in argon and nitrous oxide conditions with doses from 1 kGy up to 25 kGy with 10 kGy/h dose rate. The mean particle size (Rh) was determined by Dynamic Light Scattering (DLS) and radius of gyration (Rg) and weight-average molecular weight (Mw) by Static Light Scattering (SLS). These samples were morphologically characterized using Atomic Force Microscopy (AFM) and Transmission Electron Microscopy (TEM). Samples prepared with 100 mM PVP K-90 solution formed macroscopic gels, in the samples obtained with 25 mM PVP K-90 solution there was a prevalence of intermolecular crosslinking. On the other hand, in the samples generated with 10 mM PVP K-90 solution, there was a predominance of intramolecular crosslinking demonstrated in the tendency to: decrease in the radius of gyration (Rg), in the constancy of the weight-average molecular weight (Mw), in the increase in polymer coil density (ρcoil), in the Rg/Rh ratio (shape factor) around 1.0 indicating homogenous, internally cross-linked spheres, in the high relief spherical structures observed in the AFM images and in the spherical particles with high contrast observed in the TEM images. The saturation of the samples with nitrous oxide doubled formation of hydroxyl radicals, favoring the generation of polymeric radicals. Higher average number of radicals in each macromolecule contributed to the higher number of intramolecular crosslinks.

Scalable Synthesis of Photoluminescent Single‐Chain Nanoparticles by Electrostatic‐Mediated Intramolecular Crosslinking

We report the large-scale synthesis of photoluminescent single-chain nanoparticles (SCNPs) by electrostatic-mediated intramolecular crosslinking in a concentrated solution of 40 mg mL-1 by continuous addition of the free radical initiator. Poly(vinyl benzyl chloride) was charged by quaternization with vinyl-imidazolium for the intramolecular crosslinking by using 2,2-dimethoxy-2-phenylacetophenone (DMAP) as the radical initiator. Under the electrostatic repulsion thus interchain isolation, the intrachain crosslinking experiences the transition from coil through pearl-necklace to globular state. The SCNPs demonstrate strong photoluminescence in the visible range when the non-emissive units are confined thereby. Composition and microstructure of the SCNPs are tunable. The photoluminescent tadpole-like Janus SCNP can be used to selectively illuminate interfacial membranes while stabilizing the emulsions.

Scalable Synthesis of Photoluminescent Single‐Chain Nanoparticles by Electrostatic‐Mediated Intramolecular Crosslinking

AbstractWe report the large‐scale synthesis of photoluminescent single‐chain nanoparticles (SCNPs) by electrostatic‐mediated intramolecular crosslinking in a concentrated solution of 40 mg mL−1 by continuous addition of the free radical initiator. Poly(vinyl benzyl chloride) was charged by quaternization with vinyl‐imidazolium for the intramolecular crosslinking by using 2,2‐dimethoxy‐2‐phenylacetophenone (DMAP) as the radical initiator. Under the electrostatic repulsion thus interchain isolation, the intrachain crosslinking experiences the transition from coil through pearl‐necklace to globular state. The SCNPs demonstrate strong photoluminescence in the visible range when the non‐emissive units are confined thereby. Composition and microstructure of the SCNPs are tunable. The photoluminescent tadpole‐like Janus SCNP can be used to selectively illuminate interfacial membranes while stabilizing the emulsions.

Helical Foldamers and Stapled Peptides as New Modalities in Drug Discovery: Modulators of Protein-Protein Interactions

A “foldamer” is an artificial oligomeric molecule with a regular secondary or tertiary structure consisting of various building blocks. A “stapled peptide” is a peptide with stabilized secondary structures, in particular, helical structures by intramolecular covalent side-chain cross-linking. Helical foldamers and stapled peptides are potential drug candidates that can target protein-protein interactions because they enable multipoint molecular recognition, which is difficult to achieve with low-molecular-weight compounds. This mini-review describes a variety of peptide-based foldamers and stapled peptides with a view to their applications in drug discovery, including our recent progress.

Phase behavior of intrinsically disordered prion‐like domains

Phase transitions underlie cellular compartmentalization and mediate fundamental biological processes. How they are encoded in the protein sequence is therefore important. Here, we use biophysical experiments, theory, and simulations to generate a conceptual stickers‐and‐spacers framework to understand phase behavior of intrinsically disordered prion‐like low‐complexity domains (PLCDs) of RNA‐binding proteins. Stickers form non‐covalent inter‐ and intramolecular crosslinks, whereas spacers enable or suppress the formation of these crosslinks. We have previously shown that aromatic residues are the stickers in the PLCD of hnRNPA1. Here, we demonstrate that tyrosine is a stronger sticker than phenylalanine and account for interactions of charged residues. Negatively charged residues are solubilizing spacers. Arginines act as stickers through pairwise interactions with aromatic residues, while lysines weaken sticker‐sticker interactions. Low or high values of the net charge per residue weaken phase separation via mean‐field electrostatic effects, while a net charge per residue close to zero minimizes solubility and is optimal for phase separation. We further characterize the function of spacer residues, particularly that of the two most frequent spacer types glycine and serine, to ask whether serine acts as a weak sticker via its side chain. Instead, we find that increasing serine contents decreases the driving force for phase separation in agreement with the higher effective solvation volume of serine vs glycine. Our analytical and coarse‐grained models accurately predict PLCD phase behavior.

Intra- vs Intermolecular Cross-Links in Poly(methyl methacrylate) Networks Containing Enamine Bonds

The molecular dynamics of a copolymer composed of methyl methacrylate (MMA) and (2-acetoacetoxy)ethyl methacrylate (AEMA) monomers and the influence on it of intra- to intermolecular cross-links of AEMA units with ethylenediamine (EDA) was studied by combining dielectric relaxation experiments and thermal investigations. The dielectric spectra of the non-cross-linked copolymer show three dynamical processes: a slow relaxation (α) and a faster (β), both dominated by the MMA dynamics, and an even faster secondary relaxation (γ) reflecting the AEMA dynamics. Already for low cross-linking densities, the γ process is very much affected and eventually disappears, increasing the cross-linking density. The secondary β relaxation however was nearly unaffected by cross-linking. The effect of cross-linking on the α relaxation was very pronounced with an important increasing of the glass transition temperature Tg. There was also an increase of the dynamic heterogeneity and the relaxation intensity when increasing the cross-linking density (up to the maximum explored, 9 mol % EDA). The quality of the average time scale and Tg value have similarities in behavior for intra- and intermolecular cross-linking, but clear differences in the dynamic heterogeneities where observed. These differences can be interpreted in connection with the sparse internal structure of the collapsed single chains obtained by intramolecular cross-linking.

Preparation, characterization, formation mechanism and stability of allicin-loaded emulsion gel

The processing instability and strong pungent smell limit the use of allicin. To overcome these shortcomings, emulsion gels loaded with allicin were constructed using soybean protein isolate (SPI) and gum Arabic (GA) through ultrasound treatment and transglutaminase (TG) induction. The effect of ultrasonic modification and GA concentration on the physical properties of emulsion gels was investigated, and the protective effect of emulsion gel on allicin was evaluated. The results showed that ultrasonic pretreatment of SPI can significantly improve the water holding capacity, hardness, viscosity, and elasticity modulus of emulsion gels, forming denser homogeneous network structure, and these properties were best when GA concentration was 0.3%. In the process of gel formation, ultrasound can change the spatial structure of protein, the introduction of polysaccharide can enhance the hydrogen bond between molecules, and TG can promote the intramolecular crosslinking, the three worked together to form a gel network. The encapsulation efficiency of the ultrasonic SPI-GA emulsion gel can reach 70.84%, while it was only 26.63% for the SPI emulsion gel. The degradation of allicin was inhibited under strong light and high temperature. This study provides a new idea for the development of functional food rich in allicin.

Systematic Approach to Mimic Phenolic Natural Polymers for Biofabrication.

In nature, phenolic biopolymers are utilized as functional tools and molecular crosslinkers to control the mechanical properties of biomaterials. Of particular interest are phenolic proteins/polysaccharides from living organisms, which are rich in catechol and/or gallol groups. Their strong underwater adhesion is attributed to the representative phenolic molecule, catechol, which stimulates intermolecular and intramolecular crosslinking induced by oxidative polymerization. Significant efforts have been made to understand the underlying chemistries, and researchers have developed functional biomaterials by mimicking the systems. Owing to their unique biocompatibility and ability to transform their mechanical properties, phenolic polymers have revolutionized biotechnologies. In this review, we highlight the bottom-up approaches for mimicking polyphenolic materials in nature and recent advances in related biomedical applications. We expect that this review will contribute to the rational design and synthesis of polyphenolic functional biomaterials and facilitate the production of related applications.

Disentangling Component Dynamics in an All-Polymer Nanocomposite Based on Single-Chain Nanoparticles by Quasielastic Neutron Scattering.

We have investigated an all-polymer nanocomposite (NC) consisting of single-chain nanoparticles (SCNPs) immersed in a matrix of linear chains of their precursors (25/75% composition in weight). The SCNPs were previously synthesized via “click” chemistry, which induces intramolecular cross-links in the individual macromolecules accompanied by a slight shift (5–8 K) of the glass transition temperature toward higher values and a broadening of the dynamic response with respect to the raw precursor material. The selective investigation of the dynamics of the NC components has been possible by using properly isotopically labeled materials and applying quasielastic neutron scattering techniques. Results have been analyzed in the momentum transfer range where the coherent scattering contribution is minimal, as determined by complementary neutron diffraction experiments with polarization analysis. We observe the development of dynamic heterogeneity in the intermediate scattering function of the NC components, which grows with increasing time. Local motions in the precursor matrix of the NC are accelerated with respect to the reference bulk behavior, while the displacements of SCNPs’ hydrogens show enhanced deviations from Gaussian and exponential behavior compared with the pure melt of SCNPs. The resulting averaged behavior in the NC coincides with that of the pure precursor, in accordance with the macroscopic observations by differential scanning calorimetry (DSC) experiments.

Deciphering the link between evolutionarily conserved sequence features and the phase behavior of prion-like low-complexity domains

Phase transitions underlie cellular compartmentalization and mediate fundamental biological processes. How they are encoded in the protein sequence is therefore important. Here, we use biophysical experiments, theory, and simulations to generate a conceptual stickers-and-spacers framework to understand phase behavior of intrinsically disordered prion-like low-complexity domains (PLCDs) of RNA-binding proteins. Stickers form non-covalent inter- and intramolecular crosslinks, whereas spacers enable or suppress the formation of these crosslinks.

UV-cured organic–inorganic composites for highly durable and flexible antireflection coatings

In this work, we develop novel UV-cured composite antireflection films by using UV curable silsesquioxanes (GPOSS) as the organic network and acidic silica sols as the inorganic parts. The composite films can be rapidly crosslinked and solidified under UV light and UV ozone exposure, respectively. The final coatings exhibit broadband antireflective properties with average transmittance of 92.71% from 400 nm to 2000 nm, and the coatings display mechanical robustness with relative transmittance reduced of only 0.38% and 0.08% after cyclic scrubbing and tape-peeling tests. Due to synergetic effect from vigorous organic-organic intramolecular crosslinking and delicate organic–inorganic intermolecular crosslinking, the coatings achieve good environmental durability with negligible optical loss after 48 h HAST test. By this design, the present UV cured composites pave the way to select novel functional materials for robust flexible antireflection use. And the method in this work opens up prospective opportunities for large-scale, flexible, and rapid coating preparation with multiple performances, which can be used to transparent displays and various flexible opto-electronic devices.

3D self-assemble formation of molybdenum disulfide (MoS<sub>2</sub>)-doped polyacrylamide (PAAm) composite hydrogels

Polyacrylamide (PAAm), a renowned member of the hydrogel class, has many uses throughout a wide range of industrial processes, including water absorbed diapers, contact lenses, wastewater treatment, biomedical applications such as drug delivery vehicles and tissue engineering because of its physical stability, durability, flexibility easier shaping, and so on. PAAm also provides new functionalities after the incorporation of inorganic structures such as molybdenum disulfide (MoS2). During the copolymerization process, the transmittance of all samples reduced significantly after a particular time, referred to as the gel point. Microgels form a tree above the gel point as projected by Flory-Stockmayer classical theory. Because of microgels positioned at the junction points of the Cayley tree, the addition of MoS2 results in strong intramolecular crosslinking and looser composites. Moreover, fractal geometry provides a quantitative measure of randomness and thus permits characterization of random systems such as polymers. Fractal dimension of these polymer composites is calculated from power-law-dependent scattered intensity. It was also confirmed that a hydrogel rapidly formed within a few seconds, indicating a 3D network formation inside the gel. These materials may have a great potential for application in wearable and implantable electronics due to this highly desired 3D self-assemble feature.