Estimation of optimal parameters yielding target amplitude–frequency response in nonlinear vibrating systems by a generalised cluster-based algorithm

Nonlinear Dynamics - Optimisation procedures for nonlinear vibrating systems are made cumbersome due to the fact that the regimes of periodic response are not known beforehand. Moreover, such...     

Enantioselective LC–ESI–MS/MS method for quantitation of (−)-lumefantrine and (+)-lumefantrine in mice plasma and application to a pharmacokinetic study

We developed and validated a simple, sensitive, selective, and reliable LC–MS/MS–ESI method for the direct quantitation of lumefantrine (LFN) enantiomers [(−)-LFN and (+)-LFN] in mice plasma as per regulatory guideline. LFN enantiomers and carbamazepine (internal standard) were extracted from mice plasma using Strata X SPE (solid-phase extraction) cartridges. Good resolution between enantiomers was achieved on a Chiralpak IA-3 column using an isocratic mobile phase (0.1% of diethyl amine in methanol), which was delivered at a flow rate of 0.8 mL/min. Detection and quantitation were performed using multiple reaction monitoring mode following the transitions m/z 530.27 → 512.30 and 237.00 → 194.00 for LFN enantiomers and the internal standard, respectively, in the positive-ionization mode. The proposed method provided accurate and reproducible results over the linearity range of 2.39–895 ng/mL for each enantiomer. The intra- and inter-day precisions were in the range of 1.03–6.14 and 6.36–8.70 and 2.03–4.88 and 5.82–11.5 for (−)-LFN and (+)-LFN, respectively. Both (−)-LFN and (+)-LFN were found to be stable under different stability conditions. The method was successfully used to delineate stereoselective pharmacokinetics of LFN enantiomers in mice after an oral administration of rac-LFN (20 mg/kg). The pharmacokinetic results indicated that the disposition of LFN enantiomers was stereoselective in mice.     

Analytical and numerical solution of an $$\varvec{n}$$n-term fractional nonlinear dynamic oscillator

Nonlinear Dynamics - This work presents a novel method for the analytical and numerical solution of an n-term fractional nonlinear dynamical system. Two simple methods, commonly known to vibration...     

N,N′-Ethylene-Bridged Bis-2-Aryl-Pyrrolinium Cations to E-Diaminoalkenes: Non-Identical Stepwise Reversible Double-Redox Coupled Bond Activation Reactions

This work presents a stepwise reversible two-electron transfer induced hydrogen shift leading to the conversion of a bis-pyrrolinium cation to an E-diaminoalkene and vice versa. Remarkably, the forward and the reverse reaction, which are both reversible, follow two completely different reaction pathways. Establishing such unprecedented property in this type of processes was possible by developing a novel synthetic route towards the starting dication. All intermediates involved in both the forward and the backward reactions were comprehensively characterized by a combination of spectroscopic, crystallographic, electrochemical, spectroelectrochemical, and theoretical methods. The presented synthetic route opens up new possibilities for the generation of multi-pyrrolinium cation scaffold-based organic redox systems, which constitute decidedly sought-after molecules in contemporary chemistry.     

Enantioselective LC‐ESI‐MS/MS determination of dropropizine enantiomers in rat plasma and application to a pharmacokinetic study

We developed and validated a simple, sensitive, selective and reliable LC–ESI‐MS/MS method for direct quantitation of dropropizine enantiomers namely levodropropizine (LDP) and dextrodropropizine (DDP) in rat plasma without the need for derivatization as per regulatory guidelines. Dropropizine enantiomers and carbamazepine (internal standard) were extracted from 50 μL rat plasma using ethyl acetate. LDP and DDP resolved with good baseline separation (R_s = 4.45) on a Chiralpak IG‐3 column. The mobile phase consisted of methanol with 0.05% diethylamine pumped at a flow rate of 0.5 mL/min. Detection and quantitation were done in multiple reaction monitoring mode following the transitions m/z 237 → 160 and 237 → 194 for dropropizine enantiomers and the internal standard, respectively, in the positive ionization mode. The proposed method provided accurate and reproducible results over the linearity range of 3.23–2022 ng/mL for each enantiomer. The intra‐ and inter‐day precisions were in the ranges of 3.38–13.6 and 5.11–13.8 for LDP and 4.19–11.8 and 8.89–10.1 for DDP. Both LDP and DDP were found to be stable under different stability conditions. The method was successfully used in a stereoselective pharmacokinetic study of dropropizine enantiomers in rats following oral administration of racemate dropropizine at 100 mg/kg. The pharmacokinetic results indicate that the disposition of dropropizine enantiomers is not stereoselective and chiral inversion does not occur in rats.     

Sulfonyl fluorides as privileged warheads in chemical biology

Sulfonyl fluoride electrophiles have found significant utility as reactive probes in chemical biology and molecular pharmacology. As warheads they possess the right balance of biocompatibility (including aqueous stability) and protein reactivity. Their functionality is privileged in this regard as they are known to modify not only reactive serines (resulting in their common use as protease inhibitors), but also context-specific threonine, lysine, tyrosine, cysteine and histidine residues. This review describes the application of sulfonyl fluoride probes across various areas of research and explores new approaches that could further enhance the chemical biology toolkit. We believe that sulfonyl fluoride probes will find greater utility in areas such as covalent enzyme inhibition, target identification and validation, and the mapping of enzyme binding sites, substrates and protein–protein interactions.     

Triazine interlinked covalent organic polymer as an efficient anti-bacterial agent

Herein, we report the synthesis of new covalent organic polymer comprising triazine and o-tolidine by solvothermal method. The formation of polymer was confirmed by Fourier transform infra red spectroscopy (FT-IR), cross polarization–magic angle spinning nuclear magnetic resonance (NMR), transmission electron microscopy, and scanning electron microscopy. Their antibacterial activity toward S. aureus (gram-positive) and P. aeruginosa (gram-negative) was assessed by the optical density measurements and direct contact method. These results have great significance toward the design of new porous polymers for antibacterial applications.     

Accurate numerical estimation of interphase momentum transfer in Lagrangian–Eulerian simulations of dispersed two-phase flows

The Lagrangian–Eulerian (LE) approach is used in many computational methods to simulate two-way coupled dispersed two-phase flows. These include averaged equation solvers, as well as direct numerical simulations (DNS) and large-eddy simulations (LES) that approximate the dispersed-phase particles (or droplets or bubbles) as point sources. Accurate calculation of the interphase momentum transfer term in LE simulations is crucial for predicting qualitatively correct physical behavior, as well as for quantitative comparison with experiments. Numerical error in the interphase momentum transfer calculation arises from both forward interpolation/approximation of fluid velocity at grid nodes to particle locations, and from backward estimation of the interphase momentum transfer term at particle locations to grid nodes. A novel test that admits an analytical form for the interphase momentum transfer term is devised to test the accuracy of the following numerical schemes: (1) fourth-order Lagrange Polynomial Interpolation (LPI-4), (3) Piecewise Cubic Approximation (PCA), (3) second-order Lagrange Polynomial Interpolation (LPI-2) which is basically linear interpolation, and (4) a Two-Stage Estimation algorithm (TSE). A number of tests are performed to systematically characterize the effects of varying the particle velocity variance, the distribution of particle positions, and fluid velocity field spectrum on estimation of the mean interphase momentum transfer term. Numerical error resulting from backward estimation is decomposed into statistical and deterministic (bias and discretization) components, and their convergence with number of particles and grid resolution is characterized. It is found that when the interphase momentum transfer is computed using values for these numerical parameters typically encountered in the literature, it can incur errors as high as 80% for the LPI-4 scheme, whereas TSE incurs a maximum error of 20%. The tests reveal that using multiple independent simulations and higher number of particles per cell are required for accurate estimation using current algorithms. The study motivates further testing of LE numerical methods, and the development of better algorithms for computing interphase transfer terms.     

Parametric identification of nonlinear systems using multiple trials

It is observed that the harmonic balance (HB) method of parametric identification of nonlinear system may not give right identification results for a single test data. A multiple-trial HB scheme is suggested to obtain improved results in the identification, compared with a single sample test. Several independent tests are conducted by subjecting the system to a range of harmonic excitations. The individual data sets are combined to obtain the matrix for inversion. This leads to the mean square error minimization of the entire set of periodic orbits. It is shown that the combination of independent test data gives correct results even in the case where the individual data sets give wrong results.