Synthesis of (1′S*,2R*,3R*)- and (1′S*,2R*,3S*)-N-arylsulfonyl-2-(1′-halogenethyl)-3-methylindolines and their selective toxicity against SH-SY5Y cell line

N-tosyl-2- and N-tosyl-4-halogen-substituted derivatives of 2-(1-methylbut-2-en-1-yl)aniline were synthesized and their molecular iodine-mediated cyclization was investigated. The cyclization upon interaction of N-tosyl-6-methyl-2-(1-methylbut-2-en-1-yl)aniline with molecular iodine in methyl tert-butyl ether or acetonitrile was studied, as well as the interaction of this sulfonamide with N-bromosucinimide in dichloromethane. Synthesized (2R*,3R*)- and (2R*,3S*)-N-arylsulfonyl-2-(1-halogenoethyl)-3-methylindoline derivatives showed cytotoxic activity against HEK293 cells, SH-SY5Y, Jurkat, and HepG2 cell lines. The compounds (2R*,3S*)-N-arylsulfonyl-7-bromo-2-(1-halogenoethyl)-3-methylindoline cis- 4a , stereoisomeric (2R*,3R*)-trans- 4h and (2R*,3S*)-N-tosyl-7-chloro-2-(1-halogenoethyl)-3-methylindoline cis- 4h demonstrated selective toxicity against SH-SY5Y cell line (IC₅₀ ≈ 3 ÷ 5 μM), and did not affect HEK293, Jurkat, and HepG2 cells.     

Diastereoselective cycloaddition of (S)-N-(1-phenylethylimino)trifluoropropionate and trifluoroethylphosphonate with diazomethane

The cycloaddition reaction of (S)-(α-phenylethylimino)trifluoropropionate with diazomethane leads to a diastereomeric mixture (4.5:1) of 5-trifluoromethyl-1,2,3-triazoline-5-carboxylates. Enantiopure diastereomers were isolated by column chromatography and converted into their respective non-racemic 2-trifluoromethyl-aziridine-2-carboxylates and carboxylic acids. The absolute configuration of newly formed stereogenic centers was determined by XRD analysis. The stereoselective reaction between (S)-N-(α-phenylethyl)trifluoroacetimidoylphosphonate and diazomethane produces a diastereomeric mixture (2.5:1) of 5-trifluoromethyltriazoline-5-phosphonates readily separated by column chromatography in diastereomerically pure forms.     

One-step synthesis of substituted 6-amino-5-cyanospiro-4-(piperidine-4')- 2H,4H-dihydropyrazolo[3,4-b]pyrans

Three-component condensation of 4-piperidinones (7), 5-pyrazolones (8), and malononitrile (4) proceeds chemically and electrochemically and is a convenient one-step means of synthesis of substituted 6-amino-5-cyanospiro-4-(piperidine-4')-2H,4H-dihydropyrazolo[3,4-b]pyrans (12). The electrochemical reactions proceed under milder conditions and with yields 12-15% greater than those of the reactions catalyzed by chemical bases.     

Experimental determination of human erythrocyte membrane permeability coefficients for a series of amides

Erythrocyte membrane permeability coefficients have been determined for a series of amides by a method based on the physical and mathematical modelling of hypotonic haemolysis process. The results show that penetration of the substances occurs by two alternative ways through aqueous pores formed by proteins and by the direct dissolving of the molecules in membrane lipids. This conclusion can be confirmed by the correlation analysis between permeability coefficients of native erythrocytes and those pre-incubated with the monosodium salt of p-chloromercuribenzenesulfonic acid (pCMBS), and the partition coefficients of the substances in hydrophilic-hydrophobic phases. Penetration of substances through hydrophilic channels is limited by the sterical factor and diameter in particular. Permeability coefficients for erythrocytes pre-incubated with pCMBS increase in an accordance with the rise of the partition coefficients with correlation coefficient of 0.94, thereby indicating a lipid route of permeation of molecules through erythrocyte membranes.     

“Exact” and Approximate Methods for Bayesian Inference: Stochastic Volatility Case Study

We conduct a case study in which we empirically illustrate the performance of different classes of Bayesian inference methods to estimate stochastic volatility models. In particular, we consider how different particle filtering methods affect the variance of the estimated likelihood. We review and compare particle Markov Chain Monte Carlo (MCMC), RMHMC, fixed-form variational Bayes, and integrated nested Laplace approximation to estimate the posterior distribution of the parameters. Additionally, we conduct the review from the point of view of whether these methods are (1) easily adaptable to different model specifications; (2) adaptable to higher dimensions of the model in a straightforward way; (3) feasible in the multivariate case. We show that when using the stochastic volatility model for methods comparison, various data-generating processes have to be considered to make a fair assessment of the methods. Finally, we present a challenging specification of the multivariate stochastic volatility model, which is rarely used to illustrate the methods but constitutes an important practical application.     

Numerical study of an ion-exchanged glass waveguide using both two-dimensional and three-dimensional models

A numerical study is carried out to compare the two-dimensional (2-D) case and three-dimensional (3-D) case for the modelling of an ion-exchanged glass waveguide. It is shown that different waveguide widths on the photomask correspond to different ion concentration distributions after an annealing process. A numerical example is presented of two waveguide sections with different widths indicates that due to the abrupt change of the waveguide width, a 3-D theoretical model is required for an accurate prediction of the parameters of ion-exchanged glass waveguides. The good agreement between the modelled and measured results proves that the developed 3-D numerical model can be beneficially utilized in the generalized design of optical devices based on ion-exchange waveguides.     

Humidity sensor based on a single-mode hetero-core fiber structure

Using a small-core single-mode fiber (SCSMF), a novel relative humidity (RH) sensor based on an SMF28-SCSMF-SMF28 fiber structure was proposed in this paper. By depositing a humidity sensitive material, such as poly (ethylene oxide) (PEO) on the bare SCSMF fiber, the proposed structure can act as an RH sensor with high sensitivity. Experiments demonstrated that the proposed RH sensor with PEO coating can achieve a sensitivity of 430 nm per relative humidity unit (RHU) in the RH range from 80% to 83% RH and a sensitivity of 50 nm per RHU in the RH range from 83% to 95% RH.     

Fiber refractometer based on a fiber Bragg grating and single-mode-multimode-single-mode fiber structure

A refractive index (RI) sensor based on a novel fiber structure that consists of a single-mode-multimode-single-mode (SMS) fiber structure followed by a fiber Bragg grating was demonstrated. The multimode fiber in the SMS structure excites cladding modes within output single-mode fiber (SMF) and recouple the reflected cladding Bragg wavelength to the input SMF core. By measuring the relative Bragg wavelength shift between core and cladding Bragg wavelengths, the RI can be determined. Experimentally we have achieved a maximum sensitivity of 7.33 nm/RIU (RI unit) at RI range from 1.324 to 1.439.