Novel tacrine-based acetylcholinesterase inhibitors as potential agents for the treatment of Alzheimer’s disease: Quinolotacrine hybrids

A new series of quinolotacrine hybrids including cyclopenta- and cyclohexa-quinolotacrine derivatives were designed, synthesized, and assessed as anti-cholinesterase (ChE) agents. The designed derivatives indicated higher inhibitory effect on the acetylcholinesterase (AChE) with IC₅₀ values of 0.285–100 µM compared to butyrylcholinesterase (BChE) with IC₅₀ values of?>?100 µM. Of these compounds, cyclohexa-quinolotacrine hybrids displayed a little better anti-AChE activity than cyclopenta-quinolotacrine hybrids. Compound 8-amino-7-(3-hydroxyphenyl)-5,7,9,10,11,12-hexahydro-6H-pyrano[2,3-b:5,6-c'] diquinolin-6-one (6m) including 3-hydroxyphenyl and cyclohexane ring moieties exhibited the best AChE inhibitory activity with IC₅₀ value of 0.285 µM. The kinetic and molecular docking studies indicated that compound 6m occupied both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE as a mixed inhibitor. Using neuroprotective assay against H₂O₂-induced cell death in PC12 cells, the compound 6h illustrated significant protection among the assessed compounds. In silico ADME studies estimated good drug-likeness for the designed compounds. As a result, these quinolotacrine hybrids can be very encouraging AChE inhibitors to treat Alzheimer’s disease.

Graphic abstract

A novel series of quinolotacrine hybrids were designed, synthesized, and evaluated against AChE and BChE enzymes as potential agents for the treatment of AD. The hybrids showed good to significant inhibitory activity against AChE (0.285–100 μM) compared to butyrylcholinesterase (BChE) with IC₅₀ values of?>?100 μM. Among them, compound 8-amino-7-(3-hydroxyphenyl)-5,7,9,10,11,12-hexahydro-6H-pyrano[2,3-b:5,6-c′] diquinolin-6-one (6 m) bearing 3-hydroxyphenyl moiety and cyclohexane ring exhibited the highest anti-AChE activity with IC₅₀ value of 0.285 μM. The kinetic and molecular docking studies illustrated that compound 6 m is a mixed inhibitor and binds to both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE.

     

High-dimensional quantum dynamical study of the dissociation of H2 on Pd110

We report the first six-dimensional quantum dynamical study of the dissociative adsorption of H(2) on a (110) surface. We have performed quantum coupled-channel calculations for the system H(2)/Pd(110) based on a potential energy surface (PES) that was derived from ab initio electronic structure calculations. In particular, we have focused on the effects of the corrugation and anisotropy of the PES on the H(2) dissociation probability. Our results agree well with the available experimental data for the sticking probability as a function of the initial kinetic energy and the angle of incidence. Because of the coupling between the anisotropy and corrugation of the potential energy surface our calculations predict an unusual rotational heating and a rather small rotational alignment in desorption.     

“Confinement effects for nano-electrocatalysts for oxygen reduction reaction”

Oxygen reduction reaction (ORR) is one of the most technologically relevant reactions. It occurs at the interface of the electrocatalyst and electrolyte, where oxygen reacts with protons and electrons to produce water. Because the electrocatalyst is dispersed on a high surface area support, morphological confinement becomes critical, as it dictates proton and oxygen transport. Furthermore, confinement is induced by ionomer, ionic liquids (ILs), or molecular additives, and their impact on electrocatalyst reactivity and transport properties is currently not well understood. We present an overview of electrostatics and mass transport–induced confinement and zoom in into ILs and molecular additives and try to unravel how local confinement induced by them impacts ORR.     

Functionalization of Multi Carbon Nanotubes with 1,2‐Naphthoquinone‐4‐sulfonic Acid Sodium: A Novel Sulphydryl Compounds Sensor Based on Functionalized Carbon Nanotube Film Using Michael Addition

The functionalized multi‐wall carbon nanotube with 1,2‐naphthoquinone‐4‐sulfonic acid sodium (Nq‐MWNT) was fabricated by a simple and low‐cost method. Techniques of scanning electron microscope (SEM) with energy dispersive X‐ray (EDX) analysis, fourier transform infrared spectroscopy (FT‐IR), ultraviolet visible spectroscopy (UV‐vis) and cyclic voltammetry (CV) were used to characterize the property of the Nq‐MWNT. The results showed that the MWNT with high functionalization of Nq can be obtained using this simple method. The Nq‐MWNT modified carbon paste electrode (Nq‐MWNT/CPE) was fabricated by drop‐casting technique. The resulted modified electrode was tested successfully to detection D‐penicillamine (D‐PA) and captopril (CAP) in an aqueous solution. It is found that D‐PA and CAP participate in Michael addition reaction with Nq on MWNT to form the corresponding thioquinone derivative. The reoxidation of adducts at a potential of less positive than D‐PA and CAP at the surface of the bare CPE leads to an increase in the oxidative current, which is proportional to the concentration of D‐PA and CAP. The catalytic response showed a wide linear range (3‐200 μM and 1‐130 μM for D‐PA and CAP, respectively) as well as its experimental limit of detection can be achieved 0.8 μM, and 0.4 μM for D‐PA and CAP, respectively. The modified electrode for D‐PA and CAP determination is of the property of simple preparation, good stability and high sensitivity. Furthermore, the fabricated electrode was used to determine the content of D‐PA and CAP in the tablet, suggesting the good accuracy of the method.     

Theoretical Study and NBO Analysis of the Decomposition Kinetics of Oxetane, 2-Methyloxetane and 2,2-Dimethyloxetane

A theoretical study of the thermal decomposition kinetics of oxetane (1), 2-methyloxetane (2), and 2,2-dimethyloxetane (3) has been carried out at the B3LYP/6-311+G**, B3PW91/6-311+G**, and MPW1PW91/6-311+G** levels of theory. The MPW1PW91/6-311+G** method was found to give a reasonable good agreement with the experimental kinetics and thermodynamic parameters. The decomposition reaction of compounds 1～3 yields formaldehyde and the corresponding substituted olefin. Based on the optimized ground state geometries using MPW1PW91/6-311+G** method, the natural bond orbital (NBO) analysis of donor-acceptor (bond-antibond) interactions revealed that the stabilization energies associated with the electronic delocalization from σC3-C4 bonding to σ*O1-C2 antibonding orbitals decrease from compounds 1 to 3. The σC3-C4→σO1-C2 resonance energies for compounds 1～3 are 2.63, 2.59 and 2.45 kcal mol-1, respectively. Further, the results showed that the energy gaps between σC3-C4 bonding and σ*O1-C2 antibonding orbitals decrease from compounds 1 to 3. Also, the decomposition process in these compounds are controlled by σ→σ* resonance energies. Moreover, the obtained order of energy barriers could be explained by the number of electron-releasing methyl groups substituted to the Csp3 atom (which is attached to oxygen atom). NBO analysis shows that the occupancies of σCsp3-O bonds decrease for compounds 1～3 as 3<2<1, and those of σCsp3-O bonds increase in the opposite order (3 > 2 > 1). This fact illustrates a comparatively easier thermal decomposition of the sCsp3-O bond in compound 3 compared to compound 2, and in compound 2 compared to compound 1. NBO results indicate that these reactions are occurring through a concerted and asynchronous four-membered cyclic transition state type of mechanism.     

Mg-catalyzed one-pot preparation of benzimidazoles and spirooxindoles by an immobilized chlorophyll b on magnetic nanoparticles

Chlorophyll b was extracted from Heliotropium europaeum plant, then immobilized on magnetic nanoparticles (Fe₃O₄@SiO₂@Chl-Mg) and found as an efficient and green catalyst for the preparation of a variety of benzimidazoles and spirooxindoles in mild conditions. The catalyst was fully characterized by Fourier-transform infrared (FTIR), ultraviolet–visible (UV–vis) spectroscopy, X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric (TGA), vibrating sample magnetometer (VSM), transmission electron microscopy (TEM), and dynamic light scattering (DLS) analyses. To prove the catalytic influence of Mg over the reactions, the catalytic activity of the demetalated chlorophyll b as well as some other control experiments was investigated. High to excellent yields were achieved for all entries, whether benzimidazole or spirooxindole derivatives at short reaction times. The catalyst could be recovered and reused for several consecutive runs by a simple external magnetic field without any considerable reactivity loss. The properties of the recovered catalyst were investigated by various analyses. Finally, the reasonable mechanisms were proposed for the reactions based on the literature.     

Photocatalytic activity of ZrO2 nanoparticles prepared by electrical arc discharge method in water

ZrO₂ nanoparticles were synthesized through arc discharge of zirconium electrodes in deionized (DI) water. X-ray diffraction (XRD) analysis of the as prepared nanoparticles indicates formation a mixture of nanocrystalline ZrO₂ monoclinic and tetragonal phase structures. Transmission electron microscopy (TEM) images illustrate spherical ZrO₂ nanoparticles with 7–30 nm diameter range, which were formed during the discharge process with 10 A arc current. The average particle size was found to increase with the increasing arc current. X-ray photoelectron spectroscopy (XPS) analysis confirms formation of ZrO₂ at the surface of the nanoparticles. Surface area of the sample prepared at 10 A arc current, measured by BET analysis, was 44 m²/g. Photodegradation of Rhodamine B (Rh. B) shows that the prepared samples at lower currents have a higher photocatalytic activity due to larger surface area and smaller particle size.