A gadolinium-based magnetic ionic liquid for supramolecular dispersive liquid–liquid microextraction followed by HPLC/UV for the determination of favipiravir in human plasma

Favipiravir is a potential antiviral medication that has been recently licensed for Covid-19 treatment. In this work, a gadolinium-based magnetic ionic liquid was prepared and used as an extractant in dispersive liquid–liquid microextraction (DLLME) of favipiravir in human plasma. The high enriching ability of DLLME allowed the determination of favipiravir in real samples using HPLC/UV with sufficient sensitivity. The effects of several variables on extraction efficiency were investigated, including type of extractant, amount of extractant, type of disperser and disperser volume. The maximum enrichment was attained using 50 mg of the Gd-magnetic ionic liquid (MIL) and 150 μl of tetrahydrofuran. The Gd-based MIL could form a supramolecular assembly in the presence of tetrahydrofuran, which enhanced the extraction efficiency of favipiravir. The developed method was validated according to US Food and Drug Administration bioanalytical method validation guidelines. The coefficient of determination was 0.9999, for a linear concentration range of 25 to 1.0 × 10⁵ ng/ml. The percentage recovery (accuracy) varied from 99.83 to 104.2%, with RSD values (precision) ranging from 4.07 to 11.84%. The total extraction time was about 12 min and the HPLC analysis time was 5 min. The method was simple, selective and sensitive for the determination of favipiravir in real human plasma.     

Calcium-based coordination polymers from a solvothermal synthesis of HKUST-1 in 3D printed autoclaves

A mixed-metal 1D coordination polymer [CaCu(HBTC)₂(H2O)₈]_n (where H₃BTC – benzene-1,3,5-tric arboxylic acid) was obtained in a solvothermal synthesis of a well-known copper-containing metal–organic framework [Cu₃(BTC)₂(H₂O)₃]_n (HKUST-1) in autoclaves 3D-printed from commercial polypropylene. This material was a source of calcium ions, apparently, leaking from a colorant (calcium carbonate) promoted by glacial acetic acid as a modulator used to produce large single crystals of HKUST-1. This finding was confirmed by elemental analysis and a model experiment that resulted in a new calcium-based 1D coordination polymer [Ca(H₂BTC)₂(H₂O)₅]_n under the same solvothermal conditions with no copper or calcium salts put into a 3D-printed autoclave.     

Fabricating Dual-Atom Iron Catalysts for Efficient Oxygen Evolution Reaction: A Heteroatom Modulator Approach

Understanding the thermal aggregation behavior of metal atoms is important for the synthesis of supported metal clusters. Here, derived from a metal–organic framework encapsulating a trinuclear Fe^III₂Fe^II complex (denoted as Fe₃) within the channels, a well-defined nitrogen-doped carbon layer is fabricated as an ideal support for stabilizing the generated iron nanoclusters. Atomic replacement of Fe^II by other metal(II) ions (e.g., Zn^II/Co^II) via synthesizing isostructural trinuclear-complex precursors (Fe₂Zn/Fe₂Co), namely the “heteroatom modulator approach”, is inhibiting the aggregation of Fe atoms toward nanoclusters with formation of a stable iron dimer in an optimal metal–nitrogen moiety, clearly identified by direct transmission electron microscopy and X-ray absorption fine structure analysis. The supported iron dimer, serving as cooperative metal–metal site, acts as efficient oxygen evolution catalyst. Our findings offer an atomic insight to guide the future design of ultrasmall metal clusters bearing outstanding catalytic capabilities.     

Solvent Influence on Cellulose 1,4‐β‐Glycosidic Bond Cleavage: A Molecular Dynamics and Metadynamics Study

We explore the influence of two solvents, namely water and the ionic liquid 1‐ethyl‐3‐methylimidazolium acetate (EmimAc), on the conformations of two cellulose models (cellobiose and a chain of 40 glucose units) and the solvent impact on glycosidic bond cleavage by acid hydrolysis by using molecular dynamics and metadynamics simulations. We investigate the rotation around the glycosidic bond and ring puckering, as well as the anomeric effect and hydrogen bonds, in order to gauge the effect on the hydrolysis mechanism. We find that EmimAc eases hydrolysis through stronger solvent–cellulose interactions, which break structural and electronic barriers to hydrolysis. Our results indicate that hydrolysis in cellulose chains should start from the ends and not in the centre of the chain, which is less accessible to solvent.     

Functional zinc(II) phthalocyanines bearing Schiff base complexes as oxidation catalysts for bleaching systems

Oxidation catalysis is used to increase the performance of hydrogen peroxide in laundry bleach applications. Bleach catalysts provide cost‐effective, energy‐saving and environmentally friendly bleach systems yielding perfect stain removal at lower temperatures. This comparative study is based on the synthesis of bis[bis(salicylhydrazonephenoxy)manganese(III)] phthalocyaninatozinc(II) ( 2 ), bis[bis(salicylhydrazonephenoxy)cobalt(III)] phthalocyaninatozinc(II) ( 3 ) and bis[bis(salicylhydrazonephenoxy)iron(III)] phthalocyaninatozinc(II) ( 4 ) as tri‐nuclear complexes consisting of two Schiff base complexes substituting a zinc phthalocyanine. Complexion on the periphery to obtain complexes 2 , 3 , 4 was performed through the reaction of a Schiff base‐substituted phthalocyanine using MnCl₂?4H₂O, CoCl₂?6H₂O or FeCl₃?6H₂O salts in basic condition in dimethylformamide. Fourier transform infrared, ¹H NMR, ¹³C NMR, UV–visible, inductively coupled plasma optical emission and mass spectra were applied to characterize the prepared compounds. The bleach performances of the three phthalocyanine compounds 2 , 3 , 4 were examined by the degradation of morin as hydrophilic dye. The degradation progress in the presence of catalysts 2 , 3 , 4 /H₂O₂ combination in aqueous solution was investigated using an online spectrophotometric method. It was found that the catalysts 2 , 3 , 4 exhibited better bleaching performance at 25 °C than tetraactylethylethylenediamine as bleach activator used in powder detergent formulations for stain removal. Copyright © 2015 John Wiley & Sons, Ltd.     

Multi-Interactions in Ionic Liquids for Natural Product Extraction

Natural products with a variety of pharmacological effects are important sources for commercial drugs, and it is very crucial to develop effective techniques to selectively extract and isolate bioactive natural components from the plants against the background of sustainable development. Ionic liquids (ILs) are a kind of designable material with unique physicochemical properties, including good thermal stability, negligible vapor pressure, good solvation ability, etc. ILs have already been used in pharmaceuticals for extraction, purification, drug delivery, etc. It has been reported that multi-interactions, like hydrogen bonding, hydrophobic interactions, play important roles in the extraction of bioactive components from the plants. In this review, recent progress in the understanding of scientific essence of hydrogen bonding, the special interaction, in ILs was summarized. The extraction of various natural products, one important area in pharmaceutical, by conventional and functional ILs as well as the specific roles of multi-interactions in this process were also reviewed. Moreover, problems existing in bioactive compound extraction by ILs and the future developing trends of this area are given, which might be helpful for scientists, especially beginners, in this field.     

Synthesis and Characterization of 5‐Cyanotetrazolide‐Based Ionic Liquids

New salts based on imidazolium, pyrrolidinium, phosphonium, guanidinium, and ammonium cations together with the 5‐cyanotetrazolide anion [C₂N₅]^? are reported. Depending on the nature of cation–anion interactions, characterized by XRD, the ionic liquids (ILs) have a low viscosity and are liquid at room temperature or have higher melting temperatures. Thermogravimetric analysis, cyclic voltammetry, viscosimetry, and impedance spectroscopy display a thermal stability up to 230 °C, an electrochemical window of 4.5 V, a viscosity of 25 mPa s at 20 °C, and an ionic conductivity of 5.4 mS cm^?1 at 20 °C for the IL 1‐butyl‐1‐methylpyrrolidinium 5‐cyanotetrazolide [BMPyr][C₂N₅]. On the basis of these results, the synthesized compounds are promising electrolytes for lithium‐ion batteries.     

Eco‐friendly ionic liquid assisted capillary electrophoresis and α‐acid glycoprotein‐assisted liquid chromatography for simultaneous determination of anticancer drugs in human fluids

In the current work, two eco‐friendly analytical methods based on capillary electrophoresis (CE) and reversed phase liquid chromatography (RPLC) were developed for simultaneous determination of the most commonly used anticancer drugs for Hodgkin's disease: methotrexate (MTX), vinblastine, chlorambucil and dacarbazine. A background electrolyte (BGE) of 12.5 mmol/L phosphate buffer at pH 7.4 and 0.1 µmol/L 1‐butyl‐3‐methyl imidazolium bromide (BMImBr) ionic liquid (IL) was used for CE measurements at 250 nm detection wavelength, 20 kV applied voltage and 25 °C. The rinsing protocol was significantly improved to reduce the adsorption of IL on the interior surface of capillary. Moreover, RPLC method was developed on α‐1‐acid glycoprotein (AGP) column. Mobile phase was 10 mmol/L phosphate buffer at pH 6.0 (100% v/v) and flow rate at 0.1 mL/min. As AGP is a chiral column, it was successfully separated l ‐MTX from its enantiomer impurity d ‐MTX. Good linearity of quantitative analysis was achieved with coefficients of determinations (r²) >0.995. The stability of drugs measurements was investigated with adequate recoveries up to 24 h storage time under ambient temperature. The limits of detection were <50 and 90 ng/mL by CE and RPLC, respectively. The using of short‐chain IL as an additive in BGE achieved 600‐fold sensitivity enhancement compared with conventional Capillary Zone Electrophoresis (CZE). Therefore, for the first time, the proposed methods were successfully applied to determine simultaneously the analytes in human plasma and urine samples at clinically relevant concentrations with fast and simple pretreatments. Developed IL‐assisted CE and RPLC methods were also applied to measure MTX levels in patients’ samples over time. Copyright © 2014 John Wiley & Sons, Ltd.     

Identification of metabolites of rupestonic acid in rat urine by liquid chromatography combined with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry

Rupestonic acid, a potential anti‐influenza agent, is an important and characteristic compound in Artemisia rupestris L., a well‐known traditional Uighur medicine for the treatment of colds. In the present study, high‐performance liquid chromatography combined with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry was used to detect and identify the metabolites in rat urine after oral administration of rupestonic acid. A total of 10 metabolites were identified or partially characterized. The structure elucidations of the metabolites were performed by comparing the changes in accurate molecular masses and fragment ions with those of the parent compound. The results showed that the main metabolites of rupestonic acid in rat urine were formed by oxidation, hydrogenation and glucuronidation. A metabolism pathway was proposed for the first time based on the characterized structures. This metabolism study can provide essential information for drug discovery, design and clinical application of rupestonic acid. Copyright © 2014 John Wiley & Sons, Ltd.     

Tuning the Basicity of Cyano‐Containing Ionic Liquids to Improve SO2 Capture through Cyano–Sulfur Interactions

A new approach has been developed to improve SO₂ sorption by cyano‐containing ionic liquids (ILs) through tuning the basicity of ILs and cyano–sulfur interaction. Several kinds of cyano‐containing ILs with different basicity were designed, prepared, and used for SO₂ capture. The interaction between these cyano‐containing ILs and SO₂ was investigated by FTIR and NMR methods. Spectroscopic investigations and quantum chemical calculations showed that dramatic effects on SO₂ capacity originate from the basicity of the ILs and enhanced cyano–sulfur interaction. Furthermore, the captured SO₂ was easy to release by heating or bubbling N₂ through the ILs. This efficient and reversible process, achieved by tuning the basicity of ILs, is an excellent alternative to current technologies for SO₂ capture.