Potential Therapeutic Target Protein Tyrosine Phosphatase-1B for Modulation of Insulin Resistance with Polyphenols and Its Quantitative Structure–Activity Relationship

The increase in the number of cases of type 2 diabetes mellitus (T2DM) and the complications associated with the side effects of chemical/synthetic drugs have raised concerns about the safety of the drugs. Hence, there is an urgent need to explore and identify natural bioactive compounds as alternative drugs. Protein tyrosine phosphatase 1B (PTP1B) functions as a negative regulator and is therefore considered as one of the key protein targets modulating insulin signaling and insulin resistance. This article deals with the screening of a database of polyphenols against PTP1B activity for the identification of a potential inhibitor. The research plan had two clear objectives. Under first objective, we conducted a quantitative structure–activity relationship analysis of flavonoids with PTP1B that revealed the strongest correlation (R² = 93.25%) between the number of aromatic bonds (naro) and inhibitory concentrations (IC₅₀) of PTP1B. The second objective emphasized the binding potential of the selected polyphenols against the activity of PTP1B using molecular docking, molecular dynamic (MD) simulation and free energy estimation. Among all the polyphenols, silydianin, a flavonolignan, was identified as a lead compound that possesses drug-likeness properties, has a higher negative binding energy of −7.235 kcal/mol and a pKd value of 5.2. The free energy-based binding affinity (ΔG) was estimated to be −7.02 kcal/mol. MD simulation revealed the stability of interacting residues (Gly183, Arg221, Thr263 and Asp265). The results demonstrated that the identified polyphenol, silydianin, could act as a promising natural PTP1B inhibitor that can modulate the insulin resistance.     

2‐(2‐Naphthyloxy)acetate derivatives. I. A new class of antiamnesic agents

The title compounds 1‐(2‐naphthyloxymethylcarbonyl)piperidine, C₁₇H₁₉NO₂, (I), and 3‐methyl‐1‐(2‐naphthyl­oxy­methyl­carbonyl)­piperidine, C₁₈H₂₁NO₂, (II), are potential antiamnesics. In (II), the methyl‐substituted piperidine ring is disordered over two conformations. The piperidine ring has a chair conformation in both compounds. In (I), the mol­ecules are linked by weak intermolecular C—H⃛O interactions to give networks represented by C(4), C(6) and (18) graph‐set motifs, while in (II), weak intermolecular C—H⃛O interactions generate (5), C(4) and C(7) graph‐set motifs. The dihedral angle between the naphthalene moiety and the piperidine ring is 33.83 (7)° in (I), while it is 31.78 (11) and 19.38 (19)° for the major and minor conformations, respectively, in (II).     

N-Heterocyclic Carbene-Catalyzed Formal [6+2] Annulation Reaction via Cross-Conjugated Aza-Trienolate Intermediates

The diverse reactivity of N-heterocyclic carbenes (NHCs) in organocatalysis is due to the possibility of different modes of action. Although NHC-bound enolates and dienolates are known, the related NHC-bound cross-conjugated aza-trienolates remain elusive. Herein, we demonstrate the NHC-catalyzed formal [6+2] annulation of nitrogen-containing heterocyclic aldehydes with α,α,α-trifluoroacetophenones leading to the formation of versatile pyrrolooxazolones (29 examples). The catalytically generated cross-conjugated aza-trienolates (aza-fulvene type) underwent smooth [6+2] annulation with electrophilic ketones to afford the product in moderate to good yields under mild conditions. Preliminary DFT studies on the mechanism are also provided.     

Effect of non-homogeneity on natural frequencies of vibration of elliptic plates

This paper presents the effect of non-homogeneity of the material of plate structures on the vibration frequencies. The non-homogeneity of the plate is characterized by taking a variety of combinations of linear as well as quadratic variations in the Young’s modulus and density of the material. Boundary characteristic orthogonal polynomials using Gram-Schmidt procedure have been employed in the Rayleigh Ritz method. The results have been included for the first few frequencies of the plate element for all the boundary conditions viz. clamped, simply supported and free. Related Tables and graphs are incorporated to show the effect of the non-homogeneity parameter on the frequencies of the vibration of elliptic and circular plates.     

The Relationship between NMR Chemical Shifts of Thermally Polarized and Hyperpolarized 89Y Complexes and Their Solution Structures

Recently developed dynamic nuclear polarization (DNP) technology offers the potential of increasing the NMR sensitivity of even rare nuclei for biological imaging applications. Hyperpolarized ⁸⁹Y is an ideal candidate because of its narrow NMR linewidth, favorable spin quantum number (I= ), and long longitudinal relaxation times (T₁). Strong NMR signals were detected in hyperpolarized ⁸⁹Y samples of a variety of yttrium complexes. A dataset of ⁸⁹Y NMR data composed of 23 complexes with polyaminocarboxylate ligands was obtained using hyperpolarized ⁸⁹Y measurements or ¹H,⁸⁹Y‐HMQC spectroscopy. These data were used to derive an empirical equation that describes the correlation between the ⁸⁹Y chemical shift and the chemical structure of the complexes. This empirical correlation serves as a guide for the design of ⁸⁹Y sensors. Relativistic (DKH2) DFT calculations were found to predict the experimental ⁸⁹Y chemical shifts to a rather good accuracy.     

Quantum‐based models of charge‐dependent potential energy surfaces: Three‐state models

Quantum‐based models of how potential energies depend on charge are developed from a three‐state model, at the level of neglecting state‐to‐state overlap. The energy as a function of charge is defined as proposed previously (Valone and Atlas, J Chem Phys 2004, 120, 7262). With this definition, addition of a third state smooths the derivatives of the energy model with respect to charge at integer values of charge that are in the interior of the allowed charge range. These derivatives are related to the chemical potential. At the dissociation limit, this model converges to established limits. Another dependence is proposed that uses two different charges simultaneously. The concepts are illustrated, with calculations on an OH molecule. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2008     

Understanding the synthesis of DEGVE pulsed plasmas for application to ultra thin biocompatible interfaces

There is interest in the development of novel surface treatments for biocompatibility and non-fouling behaviors on various surfaces of in vivo devices. Polyethylene glycol thin films have shown promise as non-fouling passivation layers for such devices. Studies of the surface chemistry and non-fouling effectiveness of plasma deposited di(ethylene glycol) vinyl ether (DEGVE) films have observed that non-fouling performance is maximized when plasma deposition occurs at low values of average power, (<5 W). [Y.J. Wu, R.B. Timmons, J.S. Jen, Frank E. Molock, Non-fouling surfaces produced by gas phase pulsed plasma polymerization of an ultra low molecular weight ethylene oxide containing monomer, Colloids and Surfaces B: Biointerfaces 18 (2000) 235–248.] Chemical properties of plasma deposited films were directly attributed to the complex interactions occurring within the gas phase. In order to better understand the deposition process, as well as the significance of the conclusions drawn by Wu et al. [Y.J. Wu, R.B. Timmons, J.S. Jen, Frank E. Molock, Non-fouling surfaces produced by gas phase pulsed plasma polymerization of an ultra low molecular weight ethylene oxide containing monomer, Colloids and Surfaces B: Biointerfaces 18 (2000) 235–248.] an investigation of the gas phase behavior in DEGVE pulsed plasma discharges was performed. Infrared spectra were used to characterize the chemical composition and dissociative behavior of DEGVE plasmas across a range of average powers. This allowed for the construction of a dissociative model of the DEGVE monomer in the plasma discharge. Analysis of the observed dissociative pattern demonstrates the presence of key daughter species which would account for the observations made on deposited DEGVE films by Wu et al. [Y.J. Wu, R.B. Timmons, J.S. Jen, Frank E. Molock, Non-fouling surfaces produced by gas phase pulsed plasma polymerization of an ultra low molecular weight ethylene oxide containing monomer, Colloids and Surfaces B: Biointerfaces 18 (2000) 235–248.].     

A general and efficient Monte Carlo method for sampling intramolecular degrees of freedom of branched and cyclic molecules

A simple and easily implemented Monte Carlo algorithm is described which enables configurational-bias sampling of molecules containing branch points and rings with endocyclic and exocyclic atoms. The method overcomes well-known problems associated with sequential configurational-bias sampling methods. A "reservoir" or "library" of fragments are generated with known probability distributions dependent on stiff intramolecular degrees of freedom. Configurational-bias moves assemble the fragments into whole molecules using the energy associated with the remaining degrees of freedom. The methods for generating the fragments are validated on models of propane, isobutane, neopentane, cyclohexane, and methylcyclohexane. It is shown how the sampling method is implemented in the Gibbs ensemble, and validation studies are performed in which the liquid coexistence curves of propane, isobutane, and 2,2-dimethylhexane are computed and shown to agree with accepted values. The method is general and can be used to sample conformational space for molecules of arbitrary complexity in both open and closed statistical mechanical ensembles.     

Comprehensive Study of the Waveguide Polarizer Based on the Resonant Tunneling Effect

We examine the thickness of various layers in terms of the dependence of the loss of various modes in a waveguide polarizer based on the resonant tunneling effect. An improved method is proposed to obtain the optimum design of such a polarizer. Fabrication tolerances of the designed device are also discussed. The study should be very useful in the design of a waveguide polarizer and other devices, such as selective wavelength filters, based on the same principle.