Biocompatible and nondegradable microcapsules using an ethylamine-bridged EGCG dimer for successful therapeutic cell transplantation.

Conventional alginate microcapsules are widely used for encapsulating therapeutic cells to reduce the host immune response. However, the exchange of monovalent cations with divalent cations for crosslinking can lead to a sol-gel phase transition, resulting in gradual degradation and swelling of the microcapsules in the body. To address this limitation, we present a biocompatible and nondegradable epigallocatechin-3-gallate (EGCG)-based microencapsulation with ethylamine-bridged EGCG dimers (EGCG(d)), denoted as 'Epi-Capsules'. These Epi-Capsules showed increased physical properties and Ca2+ chelating resistance compared to conventional alginate microcapsules. Horseradish peroxidase (HRP) treatment is very effective in increasing the stability of Epi-Capsule((+)HRP) due to the crosslinking between EGCG(d) molecules. Interestingly, the Epi-Capsules(oxi) using a pre-oxidized EGCG(d) can support long-term survival (>90 days) of xenotransplanted insulin-secreting islets in diabetic mice in vivo, which is attributed to its structural stability and reactive oxygen species (ROS) scavenging for lower fibrotic activity. Collectively, this EGCG-based microencapsulation can create Ca2+ chelating-resistance and anti-oxidant activity, which could be a promising strategy for cell therapies for diabetes and other diseases.

Rapid access to polycyclic N-heteroarenes from unactivated, simple azines via a base-promoted Minisci-type annulation.

Conventional synthetic methods to yield polycyclic heteroarenes have largely relied on metal-mediated arylation reactions requiring pre-functionalised substrates. However, the functionalisation of unactivated azines has been restricted because of their intrinsic low reactivity. Herein, we report a transition-metal-free, radical relay π-extension approach to produce N-doped polycyclic aromatic compounds directly from simple azines and cyclic iodonium salts. Mechanistic and electron paramagnetic resonance studies provide evidence for the in situ generation of organic electron donors, while chemical trapping and electrochemical experiments implicate an iodanyl radical intermediate serving as a formal biaryl radical equivalent. This intermediate, formed by one-electron reduction of the cyclic iodonium salt, acts as the key intermediate driving the Minisci-type arylation reaction. The synthetic utility of this radical-based annulative π-extension method is highlighted by the preparation of an N-doped heptacyclic nanographene fragment through fourfold C-H arylation.

Investigation of the Physicochemical and Biological Stability of the Adalimumab Biosimilar CT-P17.

INTRODUCTION: CT-P17 (Celltrion, Inc., Incheon, Republic of Korea) is a biosimilar of reference adalimumab (Humira®; AbbVie Inc., North Chicago, IL, USA), which has recently received regulatory approval from the European Medicines Agency. METHODS: This analysis was designed to evaluate the stability profile of CT-P17 compared with reference adalimumab and the currently licensed adalimumab biosimilars ABP 501 (Amjevita®/Amgevita®; Amgen Inc., Thousand Oaks, CA, USA) and SB5 (Imraldi®; Biogen Inc., Cambridge, MA, USA) when stored at low temperature (5 °C) or room temperature (25 °C) with 60% relative humidity for up to 28 days. RESULTS: Multiple orthogonal and complementary tests demonstrated that CT-P17 was stable for 28 days under all tested conditions, as well as for protein concentrations tested (50 vs 100 mg/mL), type of delivery device (autoinjector vs prefilled syringe), and manufacturing date (recently manufactured vs aged for 17 months). There were slight differences among products in terms of charge variants, oxidation level, purity, and number of subvisible particles; however, overall, the quality of each product was maintained over 28 days. CONCLUSION: Our data suggest that CT-P17 may be used without any significant loss of stability when stored at 5 °C or 25 °C with 60% relative humidity for up to 28 days, and was not impacted by protein concentration tested and delivery device. Comparative stability data suggest that the appropriate maximum storage period for CT-P17 may be up to 28 days at room temperature with 60% relative humidity.

Plasticization Effect of Poly(Lactic Acid) in the Poly(Butylene Adipate-co-Terephthalate) Blown Film for Tear Resistance Improvement.

The mechanical properties and tear resistance of an ecofriendly flexible packaging film, i.e., poly(lactic acid) (PLA)/poly (butylene adipate-co-terephthalate) (PBAT) film, were investigated via a blown film extrusion process. The application of PLA and PBAT in product packaging is limited due to the high brittleness, low stiffness, and incompatibility of the materials. In this study, the effects of various plasticizers, such as adipate, adipic acid, glycerol ester, and adipic acid ester, on the plasticization of PLA and fabrication of the PLA/PBAT blown film were comprehensively evaluated. It was determined that the plasticizer containing ether and ester functionalities (i.e., adipic acid ester) improved the flexibility of PLA as well as its compatibility with PBAT. It was found that the addition of the plasticizer effectively promoted chain mobility of the PLA matrix. Moreover, the interfacial adhesion between the plasticized PLA domain and PBAT matrix was enhanced. The results of the present study demonstrated that the plasticized PLA/PBAT blown film prepared utilizing a blown film extrusion process exhibited improved tear resistance, which increased from 4.63 to 8.67 N/mm in machine direction and from 13.19 to 16.16 N/mm in the transverse direction.

Annulative π-Extension of Unactivated Benzene Derivatives through Nondirected C-H Arylation.

Annulative π-extension chemistry provides a concise synthetic route to polycyclic arenes. Herein, we disclose a nondirected annulation approach of unactivated simple arenes. The palladium-catalyzed 2-fold C-H arylation event facilitates tandem C-C linkage relays to furnish fully benzenoid triphenylene frameworks using cyclic diaryliodonium salts. The inseparable regioisomeric mixture of 1- and 2-methyltriphenylenes is identified by the combined analysis of ion mobility-mass spectrometry, gas-phase infrared spectroscopy, and molecular simulation studies.

Chemoselective Trifluoroethylation Reactions of Quinazolinones and Identification of Photostability.

Herein, we report chemoselective trifluoroethylation routes of unmasked 2-arylquinazolin-4(3 H)-ones using mesityl(2,2,2-trifluoroethyl)iodonium triflate at room temperature. Homologous C-, O-, and N-functionalized subclasses are accessed in a straightforward manner with a wide substrate scope. These chemoselective branching events are driven by Pd-catalyzed ortho-selective C-H activation at the pendant aryl ring and base-promoted reactivity modulation of the amide group, leveraging the intrinsic directing capability and competing pronucleophilicity of the quinazolin-4(3 H)-one framework. Furthermore, outstanding photostability of the quinazolin-4(3 H)-one family associated with nonradiative decay is presented.

3D Bioprinting for Artificial Pancreas Organ.

Type 1 diabetes mellitus (T1DM) results from an autoimmune destruction of insulin-producing beta cells in the islet of the endocrine pancreas. Although islet transplantation has been regarded as an ideal strategy for T1D, transplanted islets are rejected from host immune system. To immunologically protect them, islet encapsulation technology with biocompatible materials is emerged as an immuno-barrier. However, this technology has been limited for clinical trial such as hypoxia in the central core of islet bead, impurity of islet bead and retrievability from the body. Recently, 3D bioprinting has been emerged as an alternative approach to make the artificial pancreas. It can be used to position live cells in a desired location with real scale of human organ. Furthermore, constructing a vascularization of the artificial pancreas is actualized with 3D bioprinting. Therefore, it is possible to create real pancreas-mimic artificial organ for clinical application. In conclusion, 3D bioprinting can become a new leader in the development of the artificial pancreas to overcome the existed islet.

Coordination Polymers for High-Capacity Li-Ion Batteries: Metal-Dependent Solid-State Reversibility.

Electrode materials exploiting multielectron-transfer processes are essential components for large-scale energy storage systems. Organic-based electrode materials undergoing distinct molecular redox transformations can intrinsically circumvent the structural instability issue of conventional inorganic-based host materials associated with lattice volume expansion and pulverization. Yet, the fundamental mechanistic understanding of metal-organic coordination polymers toward the reversible electrochemical processes is still lacking. Herein, we demonstrate that metal-dependent spatial proximity and binding affinity play a critical role in the reversible redox processes, as verified by combined 13C solid-state NMR, X-ray absorption spectroscopy, and transmission electron microscopy. During the electrochemical lithiation, in situ generated metallic nanoparticles dispersed in the organic matrix generate electrically conductive paths, synergistically aiding subsequent multielectron transfer to π-conjugated ligands. Comprehensive screening on 3d-metal-organic coordination polymers leads to a high-capacity electrode material, cobalt-2,5-thiophenedicarboxylate, which delivers a stable specific capacity of ∼1100 mA h g-1 after 100 cycles.

Molecular Engineered Safer Organic Battery through the Incorporation of Flame Retarding Organophosphonate Moiety.

Here, we report the first electrochemical assessment of organophosphonate-based compound as a safe electrode material for lithium-ion batteries, which highlights the reversible redox activity and inherent flame retarding property. Dinickel 1,4-benzenediphosphonate delivers a high reversible capacity of 585 mA h g-1 with stable cycle performance. It expands the scope of organic batteries, which have been mainly dominated by the organic carbonyl family to date. The redox chemistry is elucidated by X-ray absorption spectroscopy and solid-state 31P NMR investigations. Differential scanning calorimetry profiles of the lithiated electrode material exhibit suppressed heat release, delayed onset temperature, and endothermic behavior in the elevated temperature zone.

Direct diversification of unmasked quinazolin-4(3H)-ones through orthogonal reactivity modulation.

Here we report a set of direct functionalization methods of unmasked 2-phenylquinazolin-4(3H)-ones, a privileged alkaloid core, without the installation/removal event of protecting groups or exogenous coordinating moieties. Divergent pathways were modulated with transition-metal catalysts by suppressing competitive reactivities, leading to N-arylation, annulative π-extension, or C-H fluorination.

Nickel-Catalyzed Azide-Alkyne Cycloaddition To Access 1,5-Disubstituted 1,2,3-Triazoles in Air and Water.

Transition-metal-catalyzed or metal-free azide-alkyne cycloadditions are methods to access 1,4- or 1,5-disubstituted 1,2,3-triazoles. Although the copper-catalyzed cycloaddition to access 1,4-disubstituted products has been applied to biomolecular reaction systems, the azide-alkyne cycloaddition to access the complementary 1,5-regioisomers under aqueous and ambient conditions remains a challenge due to limited substrate scope or moisture-/air-sensitive catalysts. Herein, we report a method to access 1,5-disubstituted 1,2,3-triazoles using a Cp2Ni/Xantphos catalytic system. The reaction proceeds both in water and organic solvents at room temperature. This protocol is simple and scalable with a broad substrate scope including both aliphatic and aromatic substrates. Moreover, triazoles attached with carbohydrates or amino acids are prepared via this cycloaddition.

An Annulative Synthetic Strategy for Building Triphenylene Frameworks by Multiple C-H Bond Activations.

C-H activation is a versatile tool for appending aryl groups to aromatic systems. However, heavy demands on multiple catalytic cycle operations and site-selectivity have limited its use for graphene segment synthesis. A Pd-catal- yzed one-step synthesis of functionalized triphenylene frameworks is disclosed, which proceeds by 2- or 4-fold C-H arylation of unactivated benzene derivatives. A Pd2 (dibenzylideneacetone)3 catalytic system, using cyclic diaryliodonium salts as π-extending agents, leads to site-selective inter- and intramolecular tandem arylation sequences. Moreover, N-substituted triphenylenes are applied to a field-effect transistor sensor for rapid, sensitive, and reversible alcohol vapor detection.

Growth of Er3+/Yb3+ co-doped CaMoO4 thin film by a spray coating and its upconverting luminescence.

Polycrystalline Er3+/Yb3+ co-doped CaMoO4 (CaMoO4:Er3+/Yb3+) film was successfully fabricated by a spray coating method. Crystal structure, surface morphology and upconversion (UC) luminescent properties were investigated. Under 980-nm excitation, CaMoO4:Er3+/Yb3+ film exhibited strong green UC emissions at 530 and 550 nm (2H,11/2 --> 4S3/2 - 4I15/2) visible to the naked eye with a weak red emission near 660 nm (4F9/2 --> 4I15/2) corresponding to the intra 4f transitions of Er3+. A possible UC mechanism related to the pump-power dependence is discussed in detail.