Covalent Mechanochemistry and Contemporary Polymer Network Chemistry: A Marriage in the Making.

Over the past 20 years, the field of polymer mechanochemistry has amassed a toolbox of mechanophores that translate mechanical energy into a variety of functional responses ranging from color change to small-molecule release. These productive chemical changes typically occur at the length scale of a few covalent bonds (Å) but require large energy inputs and strains on the micro-to-macro scale in order to achieve even low levels of mechanophore activation. The minimal activation hinders the translation of the available chemical responses into materials and device applications. The mechanophore activation challenge inspires core questions at yet another length scale of chemical control, namely: What are the molecular-scale features of a polymeric material that determine the extent of mechanophore activation? Further, how do we marry advances in the chemistry of polymer networks with the chemistry of mechanophores to create stress-responsive materials that are well suited for an intended application? In this Perspective, we speculate as to the potential match between covalent polymer mechanochemistry and recent advances in polymer network chemistry, specifically, topologically controlled networks and the hierarchical material responses enabled by multi-network architectures and mechanically interlocked polymers. Both fundamental and applied opportunities unique to the union of these two fields are discussed.

Synthesis and Ring-Opening Metathesis Polymerization of a Strained trans-Silacycloheptene and Single-Molecule Mechanics of Its Polymer.

The cis- and trans-isomers of a silacycloheptene were selectively synthesized by the alkylation of a silyl dianion, a novel approach to strained cycloalkenes. The trans-silacycloheptene (trans-SiCH) was significantly more strained than the cis isomer, as predicted by quantum chemical calculations and confirmed by crystallographic signatures of a twisted alkene. Each isomer exhibited distinct reactivity toward ring-opening metathesis polymerization (ROMP), where only trans-SiCH afforded high-molar-mass polymer under enthalpy-driven ROMP. Hypothesizing that the introduction of silicon might result in increased molecular compliance at large extensions, we compared poly(trans-SiCH) to organic polymers by single-molecule force spectroscopy (SMFS). Force-extension curves from SMFS showed that poly(trans-SiCH) is more easily overstretched than two carbon-based analogues, polycyclooctene and polybutadiene, with stretching constants that agree well with the results of computational simulations.

Recent advances in the synthesis of pyrido[1,2-a]indoles.

The pyrido[1,2-a]indole unit found in many organic compounds such as natural products, pharmaceuticals, and materials, has intensively stimulated the research of new synthetic pathways giving access to this heterocyclic nucleus in very recent years. In this review, the synthesis of pyrido[1,2-a]indoles will be divided into two parts, which concern accesses to this skeleton using or not metal catalysis.

[Physicochemical property and antioxidant activity of exopolysaccharide produced by endophytic fungal Fusarium redolens 6WBY3 isolated from Fritillaria unibracteata var. wabuensis].

Objective: To study the exopolysaccharide (EPS) of endophytic fungal Fusarium redolens 6WBY3 isolated from Fritillaria unibracteata var. wabuensis (FUW) including its antioxidant activities. Methods: We isolated the EPS from the culture medium of strain 6WBY3 using the methods of degreasing with organic solvent, precipitation with ethanol, decoloration with macroporous resins, deproteinization with protease in combination with sevag reagent, desalination with dialysis and separation with DEAE-cellulose ion exchange chromatography. Then, we analyzed the EPS fractions using high-performance gel-permeation chromatography with evaporative light scattering detector (HPGPC-ELSD), ultra violet (UV) spectra, scanning electron microscope (SEM), PMP precolumn derivatization with high performance liquid chromatography (PMP-HPLC), fourier transform infrared (FT-IR) spectroscopy and 1H-nuclear magnetic resonance (1H NMR) methods. We evaluated the antioxidant activity of the EPS using DPPH and ABTS radical scavenging activities and iron ion chelating ability methods. Results: We obtained two homogeneous EPSs, namely 6WBY3EPS-3 and 6WBY3EPS-4, with the molecular weight (Mw) of 17.41×106 and 8.84×105 Da, respectively. 6WBY3EPS-3 was composed of mannose, glucose and galactose in a molar ratio of 8.16:4.96:10.00, while 6WBY3EPS-4 was composed of mannose, rhamnose, glucose and galactose in a molar ratio of 8.08:1.71:6.32:10.00. The results of SEM showed that 6WBY3EPS-3 was the irregular multilateral body, and 6WBY3EPS-4 was rules of quadrilateral body. The results of FT-IR and 1H NMR analysis exhibited that 6WBY3EPS-3 was acidic polysaccharose with abundant galactofuranose, mannofuranose and a few α-D-glucopyranose, while 6WBY3EPS-4 possessed pyranose ring mainly. Those two EPSs had anomeric hydrogen with α-(main) and ß-glycosidic configuration. Furthermore, the results of antioxidant activity suggested that both 6WBY3EPS-3 and 6WBY3EPS-4 had a weak DPPH radical scavenging ability, a moderate ABTS radical scavenging activity and a moderate iron ion chelating effect. Conclusion: The two EPSs from the endophytic fungus 6WBY3 were firstly obtained and investigated. Our investigation indicated that the EPS from 6WBY3 had the application potential as an antioxidant in medicine and food industries. In addition, this work can also provide theory reference for improving development of EPS from other endophytic fungi.

An injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug.

Many biologics have a short plasma half-life, and their conjugation to polyethylene glycol (PEG) is commonly used to solve this problem. However, the improvement in the plasma half-life of PEGylated drugs' is at an asymptote because the development of branched PEG has only had a modest impact on pharmacokinetics and pharmacodynamics. Here, we developed an injectable PEG-like conjugate that forms a subcutaneous depot for the sustained delivery of biologics. The PEG-like conjugate consists of poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA) conjugated to exendin, a peptide drug used in the clinic to treat type 2 diabetes. The depot-forming exendin-POEGMA conjugate showed greater efficacy than a PEG conjugate of exendin as well as Bydureon, a clinically approved sustained-release formulation of exendin. The injectable depot-forming exendin-POEGMA conjugate did not elicit an immune response against the polymer, so that it remained effective and safe for long-term management of type 2 diabetes upon chronic administration. In contrast, the PEG conjugate induced an anti-PEG immune response, leading to early clearance and loss of efficacy upon repeat dosing. The exendin-POEGMA depot also showed superior long-term efficacy compared to Bydureon. Collectively, these results suggest that an injectable POEGMA conjugate of biologic drugs that forms a drug depot under the skin, providing favorable pharmacokinetic properties and sustained efficacy while remaining non-immunogenic, offers significant advantages over other commonly used drug delivery technologies.

Extending BigSMILES to non-covalent bonds in supramolecular polymer assemblies.

As a machine-recognizable representation of polymer connectivity, BigSMILES line notation extends SMILES from deterministic to stochastic structures. The same framework that allows BigSMILES to accommodate stochastic covalent connectivity can be extended to non-covalent bonds, enhancing its value for polymers, supramolecular materials, and colloidal chemistry. Non-covalent bonds are captured through the inclusion of annotations to pseudo atoms serving as complementary binding pairs, minimal key/value pairs to elaborate other relevant attributes, and indexes to specify the pairing among potential donors and acceptors or bond delocalization. Incorporating these annotations into BigSMILES line notation enables the representation of four common classes of non-covalent bonds in polymer science: electrostatic interactions, hydrogen bonding, metal-ligand complexation, and π-π stacking. The principal advantage of non-covalent BigSMILES is the ability to accommodate a broad variety of non-covalent chemistry with a simple user-orientated, semi-flexible annotation formalism. This goal is achieved by encoding a universal but non-exhaustive representation of non-covalent or stochastic bonding patterns through syntax for (de)protonated and delocalized state of bonding as well as nested bonds for correlated bonding and multi-component mixture. By allowing user-defined descriptors in the annotation expression, further applications in data-driven research can be envisioned to represent chemical structures in many other fields, including polymer nanocomposite and surface chemistry.

Microencapsulation of immunoglobulin Y: optimization with response surface morphology and controlled release during simulated gastrointestinal digestion.

Immunoglobulin Y (IgY) is an effective orally administered antibody used to protect against various intestinal pathogens, but which cannot tolerate the acidic gastric environment. In this study, IgY was microencapsulated by alginate (ALG) and coated with chitooligosaccharide (COS). A response surface methodology was used to optimize the formulation, and a simulated gastrointestinal (GI) digestion (SGID) system to evaluate the controlled release of microencapsulated IgY. The microcapsule formulation was optimized as an ALG concentration of 1.56% (15.6 g/L), COS level of 0.61% (6.1 g/L), and IgY/ALG ratio of 62.44% (mass ratio). The microcapsules prepared following this formulation had an encapsulation efficiency of 65.19%, a loading capacity of 33.75%, and an average particle size of 588.75 µm. Under this optimum formulation, the coating of COS provided a less porous and more continuous microstructure by filling the cracks on the surface, and thus the GI release rate of encapsulated IgY was significantly reduced. The release of encapsulated IgY during simulated gastric and intestinal digestion well fitted the zero-order and first-order kinetics functions, respectively. The microcapsule also allowed the IgY to retain 84.37% immune-activity after 4 h simulated GI digestion, significantly higher than that for unprotected IgY (5.33%). This approach could provide an efficient way to preserve IgY and improve its performance in the GI tract.

Copper-catalyzed Direct 2-Arylation of Benzoxazoles and Benzoimidazoles with Aryl Bromides and Cytotoxicity of Products.

An efficient copper-catalyzed direct 2-arylation of benzoxazoles and benzoimidazoles with aryl bromides is presented. The CuI/PPh3-based catalyst promotes the installation of various aryl and heteroaryl groups through a C-H activation process in good to excellent yields. The cytotoxicity of obtained 2-aryl benzoxazoles (benzoimidazoles) was also evaluated and 1-methyl-2-(naphthalen-1-yl)benzoimidazole showed potential cytotoxicity.