Development of a Promising Method for Producing Oligomeric Mixture of Branched Alkylene Guanidines to Improve Substance Quality and Evaluate Their Antiviral Activity against SARS-CoV-2

This paper reports the synthesis of branched alkylene guanidines using microfluidic technologies. We describe the preparation of guanidine derivatives at lower temperatures, and with significantly less time than that required in the previously applicable method. Furthermore, the use of microfluidics allows the attainment of high-purity products with a low residual monomer content, which can expand the range of applications of this class of compounds. For all the samples obtained, the molecular-weight characteristics are calculated, based on which the optimal condensation conditions are established. Additionally, in this work, the antiviral activity of the alkylene guanidine salt against the SARS-CoV-2 virus is confirmed.     

Screening of tyrosinase inhibitors by capillary electrophoresis with immobilized enzyme microreactor and molecular docking

A new method for screening tyrosinase inhibitors from traditional Chinese medicines (TCMs) was successfully developed by capillary electrophoresis with reliable online immobilized enzyme microreactor (IMER). In addition, molecular docking study has been used for supporting inhibition interaction between enzyme and inhibitors. The IMER of tyrosinase was constructed at the outlet of the capillary by using glutaraldehyde as cross‐linker. The parameters including enzyme reaction, separation of the substrate and product, and the performance of immobilized tyrosinase were investigated systematically. Because of using short‐end injection procedure, the product and substrate were effectively separated within 2 min. The immobilized tyrosinase could remain 80% active for 30 days at 4°C. The Michaelis–Menten constant of tyrosinase was determined as 1.78 mM. Kojic acid, a known tyrosinase inhibitor, was used as a model compound for the validation of the inhibitors screening method. The half‐maximal inhibitory concentration of kojic acid was 5.55 μM. The method was successfully applied for screening tyrosinase inhibitors from 15 compounds of TCM. Four compounds including quercetin, kaempferol, bavachinin, and bakuchiol were found having inhibitory potentials. The results obtained in this work were supported by molecular docking study.     

Preparation of Metal-Immobilized Methacrylate-Based Monolithic Columns for Flow-Through Cross-Coupling Reactions

With the aim of developing efficient flow-through microreactors for high-throughput organic synthesis, in this work, microreactors were fabricated by chemically immobilizing palladium-, nickel-, iron-, and copper-based catalysts onto ligand-modified poly(glycidyl methacrylate-co-ethylene dimethacrylate) [poly(GMA-co-EDMA)] monoliths, which were prepared inside a silicosteel tubing (10 cm long with an inner diameter of 1.0 mm) and modified with several ligands including 5-amino-1,10-phenanthroline (APHEN), iminodiacetic acid (IDA), and iminodimethyl phosphonic acid (IDP). The performance of the resulting microreactors in Suzuki−Miyaura cross-coupling reactions was evaluated, finding that the poly(GMA-co-EDMA) monolith chemically modified with 5-amino-1,10-phenanthroline as a binding site for the palladium catalyst provided an excellent flow-through performance, enabling highly efficient and rapid reactions with high product yields. Moreover, this monolithic microreactor maintained its good activity and efficiency during prolonged use.     

CF3SO3H Initiated Cationic Polymerization of Diisopropenylbenzenes in Macrobatch and Microflow Systems

CF₃SO₃H was found to serve as a more superior initiator for the polymerization of diisopropenylbenzenes than the conventionally used acids such as H₂SO₄. Much faster polymerization at lower temperatures seems to be ascribed to the higher acidity of CF₃SO₃H. The use of microflow systems was also found to be effective in increasing the indane unit content, especially for 1,4‐DPB. Fast mixing and uniformity of the temperature seem to be responsible. The thus‐obtained polymers of high indane unit content serve as useful materials having high thermal resistance and low dielectric constants.

     

Defined Picogram Dose Inclusion and Release of Macromolecules using Polyelectrolyte Microcapsules

Summary: Reversible pH‐induced swelling of (PAH/PSS) polyelectrolyte microcapsules is accompanied by increased porosity, making them permeable to poly(acrylic acid) (PAA) at pH values higher than 11.2. This pH‐switchable permeability was used to encapsulate the polyanion in alkaline conditions. Relationship between starting PAA concentration in solution and amount finally being encapsulated has been established and can be used further as calibration curve. A desired amount of encapsulated polymer in the picogram range per capsule can be achieved. The loaded capsules were then used as microreactors by forming a complex between the PAA and Ca²⁺ ions.

General scheme for pH‐induced encapsulation of (PAA) in alkali condition by switching their permeability.     

Precision synthesis of acrylate multiblock copolymers from consecutive microreactor RAFT polymerizations

Well‐defined acrylate RAFT polymers and multiblock‐copolymers have been synthesized via the use of a continuous‐flow microreactor, in which polymerizations could be executed in 5?20 min reaction time. First, Poly(n‐butyl acrylate) (PnBuA) was synthesized in the micro‐flowreactor by using two different trithiocarbonate RAFT agents. Reaction time and reaction temperature were optimized and collected samples were directly studied with NMR, SEC and ESI‐MS to determine conversion, molar mass and end group fidelity. Using the continuous flow technique, highly reproducible and fast polymerizations yielded quantitatively functionalized PnBuA in a very facile and efficient manner. One batch of RAFT acrylate polymer with a molar mass of 1100 g mol^?1 and excellent end group fidelity was employed as a macro‐RAFT agent for the subsequent copolymerization with different acrylate monomers (2‐ethylhexyl acrylate, t‐butyl acrylate, n‐butyl acrylate). Using this procedure, a sequential multiblock‐copolymer (M_n = 31,200 g mol^?1, PDI = 1.46) consisting of five consecutive acrylate blocks was synthesized. This study clearly demonstrates the potential of using a continuous‐flow microreactor for subsequent RAFT polymerizations towards well‐defined multiblock‐copolymers. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013, 51, 2366–2374     

Trypsin inhibitor screening in traditional Chinese medicine by using an immobilized enzyme microreactor in capillary and molecular docking study

A trypsin immobilized enzyme microreactor was successfully prepared in capillary for studying enzyme kinetics of trypsin and online screening of trypsin inhibitors from traditional Chinese medicine through capillary electrophoresis. Trypsin was immobilized on the inner wall at the inlet of the capillary treated with polydopamine. The rest of the capillary was used as a separation channel. The parameters including the separation efficiency and the activity of immobilized trypsin were comprehensively evaluated. Under the optimal conditions, online screening of trypsin inhibitors each time can be carried out within 6 min. The Michaelis–Menten constant of immobilized trypsin was calculated to be 0.50 mM, which indicated high affinity of the immobilized trypsin for the substrate. The half‐maximal inhibitory concentration of known inhibitor of benzamidine hydrochloride hydrate as a model inhibitor was 13.32 mM. The proposed method was successfully applied to screen trypsin inhibitors from 15 compounds of traditional Chinese medicine. It has been found that baicalin showed inhibitory potency. Molecular docking study well supported the experimental result by exhibiting molecular interaction between enzyme and inhibitors.     

Fluoro‐Substituted Methyllithium Chemistry: External Quenching Method Using Flow Microreactors

The external quenching method based on flow microreactors allows the generation and use of short‐lived fluoro‐substituted methyllithium reagents, such as fluoromethyllithium, fluoroiodomethyllithium, and fluoroiodostannylmethyllithium. Highly chemoselective reactions have been developed, opening new opportunities in the synthesis of fluorinated molecules using fluorinated organometallics.