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1. Synthesis of Carbohydrate-Grafted Glycopolymers Using a Catalyst-Free, Perfluoroarylazide-Mediated Fast Staudinger Reaction

   https://doi.org/10.3390/molecules24010157  

   Ndugire, William ; Wu, Bin ; Yan, Mingdi ( January 2019 , Molecules)

   Glycopolymers have gained increasing importance in investigating glycan-lectin interactions, as drug delivery vehicles and in modulating interactions with proteins. The synthesis of these glycopolymers is still a challenging and rigorous exercise. In this regard, the highly efficient click reaction, copper (I)-catalyzed alkyne-azide cycloaddition, has been widely applied not only for its efficiency but also for its tolerance of the appended carbohydrate groups. However, a significant drawback of this method is the use of the heavy metal catalyst which is difficult to remove completely, and ultimately toxic to biological systems. In this work, we present the synthesis of carbohydrate-grafted glycopolymers utilizing a mild and catalyst-free perfluorophenyl azide (PFPA)-mediated Staudinger reaction. Using this strategy, mannose (Man) and maltoheptaose (MH) were grafted onto the biodegradable poly(lactic acid) (PLA) by stirring a PFAA-functionalized PLA with a phosphine-derivatized Man or MH in DMSO at room temperature within an hour. The glycopolymers were characterized by 1H-NMR, 19F-NMR, 31P-NMR and FTIR. 

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2. Non-Enzymatic Detection of Glucose in Neutral Solution Using PBS-Treated Electrodeposited Copper-Nickel Electrodes

   https://doi.org/10.3390/bios11110409  

   Goodnight, Lindsey ; Butler, Derrick ; Xia, Tunan ; Ebrahimi, Aida ( November 2021 , Biosensors)

   Transition metals have been explored extensively for non-enzymatic electrochemical detection of glucose. However, to enable glucose oxidation, the majority of reports require highly alkaline electrolytes which can be damaging to the sensors and hazardous to handle. In this work, we developed a non-enzymatic sensor for detection of glucose in near-neutral solution based on copper-nickel electrodes which are electrochemically modified in phosphate-buffered saline (PBS). Nickel and copper were deposited using chronopotentiometry, followed by a two-step annealing process in air (Step 1: at room temperature and Step 2: at 150 °C) and electrochemical stabilization in PBS. Morphology and chemical composition of the electrodes were characterized using scanning electron microscopy and energy-dispersive X-ray spectroscopy. Cyclic voltammetry was used to measure oxidation reaction of glucose in sodium sulfate (100 mM, pH 6.4). The PBS-Cu-Ni working electrodes enabled detection of glucose with a limit of detection (LOD) of 4.2 nM, a dynamic response from 5 nM to 20 mM, and sensitivity of 5.47 ± 0.45 μA cm−2/log10(mole.L−1) at an applied potential of 0.2 V. In addition to the ultralow LOD, the sensors are selective toward glucose in the presence of physiologically relevant concentrations of ascorbic acid and uric acid spiked in artificial saliva. The optimized PBS-Cu-Ni electrodes demonstrate better stability after seven days storage in ambient compared to the Cu-Ni electrodes without PBS treatment. 

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3. Microfluidic Synthesis of Elastomeric Microparticles: A Case Study in Catalysis of Palladium-Mediated Cross-Coupling

   Bennett, Jeffrey A ; Genzer, Jan ; Abolhasani, Milad ( October 2018 , 2018 AIChE Annual Meeting)

   Metal-mediated cross-coupling reactions offer organic chemists a wide array of stereo- and chemically-selective reactions with broad applications in fine chemical and pharmaceutical synthesis.1 Current batch-based synthesis methods are beginning to be replaced with flow chemistry strategies to take advantage of the improved consistency and process control methods offered by continuous flow systems.2,3 Most cross-coupling chemistries still encounter several issues in flow using homogeneous catalysis, including expensive catalyst recovery and air sensitivity due to the chemical nature of the catalyst ligands.1 To mitigate some of these issues, a ligand-free heterogeneous catalysis reaction was developed using palladium (Pd) loaded into a polymeric network of a silicone elastomer, poly(hydromethylsiloxane) (PHMS), that is not air sensitive and can be used with mild reaction solvents (ethanol and water).4 In this work we present a novel method of producing soft catalytic microparticles using a multiphase flow-focusing microreactor and demonstrate their application for continuous Suzuki-Miyaura cross-coupling reactions. The catalytic microparticles are produced in a coaxial glass capillary-based 3D flow-focusing microreactor. The microreactor consists of two precursors, a cross-linking catalyst in toluene and a mixture of the PHMS polymer and a divinyl cross-linker. The dispersed phase containing the polymer, cross-linker, and cross-linking catalyst is continuously mixed and then formed into microdroplets by the continuous phase of water and surfactant (sodium dodecyl sulfate) introduced in a counter-flow configuration. Elastomeric microdroplets with a diameter ranging between 50 to 300 micron are produced at 25 to 250 Hz with a size polydispersity less than 3% in single stream production. The physicochemical properties of the elastomeric microparticles such as particle swelling/softness can be tuned using the ratio of cross-linker to polymer as well as the ratio of polymer mixture to solvent during the particle formation. Swelling in toluene can be tuned up to 400% of the initial particle volume by reducing the concentration of cross-linker in the mixture and increasing the ratio of polymer to solvent during production.5 After the particles are produced and collected, they are transferred into toluene containing palladium acetate, allowing the particles to incorporate the palladium into the polymer network and then reduce the palladium to Pd0 with the Si-H functionality present on the PHMS backbones. After the reduction, the Pd-loaded particles can be washed and dried for storage or switched into an ethanol/water solution for loading into a micro-packed bed reactor (µ-PBR) for continuous organic synthesis. The in-situ reduction of Pd within the PHMS microparticles was confirmed using energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS) and focused ion beam-SEM, and TEM techniques. In the next step, we used the developed µ-PBR to conduct continuous organic synthesis of 4-phenyltoluene by Suzuki-Miyaura cross-coupling of 4-iodotoluene and phenylboronic acid using potassium carbonate as the base. Catalyst leaching was determined to only occur at sub ppm concentrations even at high solvent flow rates after 24 h of continuous run using inductively coupled plasma mass spectrometry (ICP-MS). The developed µ-PBR using the elastomeric microparticles is an important initial step towards the development of highly-efficient and green continuous manufacturing technologies in the pharma industry. In addition, the developed elastomeric microparticle synthesis technique can be utilized for the development of a library of other chemically cross-linkable polymer/cross-linker pairs for applications in organic synthesis, targeted drug delivery, cell encapsulation, or biomedical imaging. References 1. Ruiz-Castillo P, Buchwald SL. Applications of Palladium-Catalyzed C-N Cross-Coupling Reactions. Chem Rev. 2016;116(19):12564-12649. 2. Adamo A, Beingessner RL, Behnam M, et al. On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system. Science. 2016;352(6281):61 LP-67. 3. Jensen KF. Flow Chemistry — Microreaction Technology Comes of Age. 2017;63(3). 4. Stibingerova I, Voltrova S, Kocova S, Lindale M, Srogl J. Modular Approach to Heterogenous Catalysis. Manipulation of Cross-Coupling Catalyst Activity. Org Lett. 2016;18(2):312-315. 5. Bennett JA, Kristof AJ, Vasudevan V, Genzer J, Srogl J, Abolhasani M. Microfluidic synthesis of elastomeric microparticles: A case study in catalysis of palladium-mediated cross-coupling. AIChE J. 2018;0(0):1-10. 

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4. Mathematical Modelling of Reactive Inks for Additive Manufacturing of Charged Membranes

   Liu, X. ; De, R. ; Perez, A. ; Hoffman, J.R. ; Phillip, W.A. ; Dowling, A.W. ( July 2022 , Computer aided chemical engineering)

   Yamashita, Y. ; Kano, M. (Ed.)

   Patterned charged membranes with engendered useful characteristics can offer selective transport of electrolytes. Chemical patterning across the membrane surface via a physical inkjet deposition process requires precise control of the reactive-ink formulation, which enables the introduction of charged functionality to the membrane. This study develops a new dynamic mathematical model for the primary step of the batch reactive-ink formulation considering an ink mixture of copper sulphate and ascorbic acid. Nonlinear least squares parameter estimation is performed to infer three kinetic model parameters by analysing data from nine dynamic experiments simultaneously. Global sensitivity and Fisher information matrix (FIM) analyses reveal only one kinetic parameter is identifiable from time-series pH measurements. The fitted model can capture the overall nonlinear dynamics of the batch reaction and works best for initial Cu2 + concentrations between 30 and 50 mM. Time-series Cu2 + or Cu+ concentration measurements are recommended in future experiments to elucidate the kinetics of reactive-ink formulation. 

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5. Comparing Copper Catalysts in the Synthesis of 1,2,3-Triazoles via Click Chemistry

   Green Emma ; Leitschuh Ethan ; Lanorio Jocelyn ( November 2022 , Transactions of the Illinois State Academy of Science)

   Copper-catalyzed azide-alkyne cycloadditions (CuAAC) produce 1,4-disubstituted 1,2,3-triazoles, molecules that have many applications in pharmaceuticals. Click reactions are atom-efficient and produce 1,4-disubstituted triazoles selectively with high yields at room temperature. Byproducts are rarely observed, and the product is easily separated by washing, eliminating the need for purification measures such as column chromatography. We tested various copper complexes for ease of use as homogeneous catalysts at various conditions. The 1,4-disubstituted triazole products were obtained in moderate to excellent yields. The progress of reaction was determined using TLC and IR spectroscopy, and products were characterized by GC-MS and NMR spectroscopy. We found that there is little that changes the outcome of the reaction upon variations in solvent and temperature conditions. However, preliminary results show that the anion of the copper salt used in preparing the copper complexes affects the kinetics of the triazole formation. A significant finding was that copper(II)-catalyzed reactions appear to form product even in the absence of a reducing agent. 

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