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.     

Synthesis,spectral investigation and development of tetrahedral copper(II) complexes as artificial metallonucleases and antimalarial agents

Seven new copper(II) complexes of type [Cu(A)(L)]?H₂O (A = sparfloxacin, ciprofloxacin, levofloxacin, gatifloxacin, pefloxacin, ofloxacin, norfloxacin; L = 5‐[(3‐chlorophenyl)diazenyl]‐4‐hydroxy‐1,3‐thiazole‐2(3H)‐thione) were synthesized and characterized using elemental and thermogravimetric analyses, and electronic, electron paramagnetic resonance (EPR), Fourier transform infrared and liquid chromatography–mass spectroscopies. Tetrahedral geometry around copper is assigned in all complexes using EPR and electronic spectral analyses. All complexes were investigated for their interaction with herring sperm DNA utilizing absorption titration (K_b = 1.27–3.13 × 10⁵ M^?1) and hydrodynamic volume measurement studies. The studies suggest the classical intercalative mode of DNA binding. The cleavage reaction on pUC19 DNA was monitored by agarose gel electrophoresis. The results indicate that the Cu(II) complexes can more effectively promote the cleavage of plasmid DNA. The superoxide dismutase mimic activity of the complexes was evaluated by nitroblue tetrazolium assay, and the complexes catalysed the dismutation of superoxide at pH = 7.8 with IC₅₀ values in the range 0.597–0.900 μM. The complexes were screened for their in vitro antibacterial activity against five pathogenic bacteria. All the complexes are good cytotoxic agents and show LC₅₀ values ranging from 5.559 to 11.912 µg ml^?1. All newly synthesized Cu(II) complexes were also evaluated for their in vitro antimalarial activity against Plasmodium falciparum strain (IC₅₀ = 0.62–2.0 µg ml^?1). Copyright © 2015 John Wiley & Sons, Ltd.     

Path to achieving molecular dispersion in a dense reactive mixture

A uniform dispersion of reactants is necessary to achieve a complete reaction involving multicomponents. In this study, we have examined the role of plasticizer in the reaction of two seemingly unlikely reactants: a highly crystalline hexamethylenetetramine (HMTA) and a strongly hydrogen bonded phenol formaldehyde resin. By combining information from NMR, infrared spectroscopy and differential scanning calorimetry, we were able to determine the role of specific intermolecular interactions necessary for the plasticizer to dissolve the highly crystalline HMTA and to plasticize the phenol formaldehyde resin in this crosslinking reaction. The presence of the plasticizer increased the segmental mobility, disrupted the hydrogen bonded matrix, and freed the hydroxyl units, which further increased the solubility of the HMTA. Both the endothermic and exothermic transitions are accounted for in the calorimetric data obtained. For the first time, it is possible to obtain the effective molar ratio of each component needed to complete the crosslinking reaction efficiently. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 1519–1526     

Antimicrobial activity on the copolymers of 2,4‐dichlorophenyl methacrylate with methyl methacrylate: Synthesis and characterization

Copolymers of monomers 2,4‐dichlorophenyl methacrylate (2,4‐DMA) and methyl methacrylate (MMA) were synthesized with different monomer feed ratios using toluene as a solvent and 2,2′‐azobisisobutyronitrile (AIBN) as an initiator at 70 °C. The copolymers were characterized by IR‐spectroscopy, and copolymer composition was determined with UV‐spectroscopy. The linearization method of Fineman–Ross was employed to obtain the monomer reactivity ratios. The molecular weights and polydispersity indexes were determined by gel permeation chromatography (GPC). Thermogravimetric analyses of polymers were carried out in nitrogen atmosphere. The homo‐ and copolymers were tested for their antimicrobial properties against selected microorganisms. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5227–5234, 2004     

Hessian Measures III

In this paper, we continue previous investigations into the theory of Hessian measures. We extend our weak continuity result to the case of mixed k-Hessian measures associated with k-tuples of k-convex functions, on domains in Euclidean n-space, k=1,2,…,n. Applications are given to capacity, quasicontinuity, and the Dirichlet problem, with inhomogeneous terms, continuous with respect to capacity or combinations of Dirac measures.     

An efficient electrophilic N-amination utilizing in situ generated chloramine under phase transfer conditions

An efficient, one-pot, phase transfer N-amination technology was developed. The protocol utilizes chloramine, an inexpensive and safe electrophilic aminating agent potentially viable for commercial manufacturing.     

A short synthesis of (±)-tecomanine via a Pauson-Khand-based route

The N-carboethoxy precursor to (±)-tecomanine has been prepared in 11 steps from 2-methyl-1-buten-3-yne. The key step, Pauson-Khand cyclization of a methylated 5-aza-6-nonen-1-yne succeeds, but only in low yield, a consequence of the dialkyl substitution about the azaenyne framework. Nevertheless, the overall sequence to that point is one of the more efficient to be described.     

Active-constraint variable ordering for faster feasibility of mixed integer linear programs

The selection of the branching variable can greatly affect the speed of the branch and bound solution of a mixed-integer or integer linear program. Traditional approaches to branching variable selection rely on estimating the effect of the candidate variables on the objective function. We present a new approach that relies on estimating the impact of the candidate variables on the active constraints in the current LP relaxation. We apply this method to the problem of finding the first feasible solution as quickly as possible. Empirical experiments demonstrate a significant improvement compared to a state-of-the art commercial MIP solver.     

Diastereoselective formation of 2-aryl-3-arenesulfonyl 4-ethyl-1,3-oxazolidines: An X-ray crystallographic and H NMR study

N-Arylsulfonamides of (R)- and (S)-2-amino-1-butanol, on condensation with aromatic aldehydes produced diastereomerically pure 2-aryl-3-arenesulfonyl 4-ethyl-1,3-oxazolidines. The absolute configurations of one enantiomeric pair have been determined from two fully refined X-ray structures, supplemented by nmr data.