Electrochemical Synthesis of 2-Aryl-3-(2-aminoaryl)quinoxalines via Oxidative Dearomatization/Ring-Opening/Cyclization Cascade Sequence of 2-Arylindoles with 1,2-Diaminoarenes.

A straightforward method has been developed to synthesize 2-aryl-3-(2-aminoaryl) quinoxalines from 2-arylindoles and 1,2-diaminoarenes under mild electrochemical conditions. The reaction proceeds through in situ generations of 2-arylindole-3-ones under electrochemical oxidative dearomatization of 2-arylindoles, followed by a ring opening-cyclization sequence with 1,2-diaminoarenes. A series of 2-aryl-3-(2-aminoaryl) quinoxalines have been prepared with moderate to good yields (up to 75%).

Investigation of efficient photoconduction and enhanced luminescence characteristics of Ce-doped ZnO nanophosphors for UV sensors.

This study involves the single-step, mass-scale productive synthesis, photoconduction, and luminescence characteristics of pure and cerium rare-earth-ion-doped ZnO (CZO) nanophosphors with different Ce concentrations (Ce: 0, 2, 4, 6, and 8 wt.%) synthesized using the solid-state reaction method. The synthesized nanophosphors were characterized for their structural, morphological, optical, and photoconductivity (PC) properties using X-ray diffraction (XRD), field-effect scanning electron microscopy (FE-SEM), energy dispersive spectroscopy, Fourier-transform infrared (FT-IR), photoluminescence (PL), and PC measurements. The sharp diffraction peaks of XRD results exhibit the formation of crystalline hexagonal wurtzite ZnO nanostructures. The decrease in diffraction peak intensities of CZO with an increase in Ce concentrations signifies the deterioration of the ZnO crystal. FE-SEM images exhibit the good crystalline quality of nanophosphors composed of spherical- and elongated-shaped nanoparticles that are distributed consistently on the surface. The energy dispersive X-ray pattern of the 4 wt.% Ce-doped ZnO (CZO4 ) sample confirms the doping of Ce in ZnO. The presence of chemical bonds and functional groups corresponds to transmittance peaks established using FT-IR spectroscopy. Deconvoluted PL spectra show two major emission peaks, one in the UV region, which is near-band-edge, and the other in the visible region ranging from ~456 to 561 nm. In PC studies, current-voltage (I-V) and current-time (I-T) characteristics, that is, rise/decayin current under dark as well as UV light conditions, are also investigated. Efficient photoconduction is observed in CZO samples. The obtained results indicate the suitability to luminescent and photosensor applications.

Sustainable smart anti-corrosion coating materials derived from vegetable oil derivatives: a review.

Sustainable development is a critical concern in this fast-paced technological world. Therefore, it is essential to employ renewable resources to move towards sustainable development goals (SDGs). The polyols attained from renewable resources, including lignin, chitosan, vegetable oils, cellulose, etc. and the polymers derived from them have attracted the attention of the majority of researchers, both in academia and industry. The development of bio-based polymers from vegetable oils start emerging with different properties to generate a value-added system. This review will give an impression to readers about how coatings generated from vegetable oils can find a way towards better protective properties against corrosion either by using fillers or by using molecular structure modifications in the system, thus covering a range of vegetable oil-based self-healing polymers and their application in anti-corrosion coatings.

Formation of hierarchical assemblies by collagen peptides derived from fish skin and bladder and their subsequent application as antiperoxide agents in lipid-rich food.

This study attempts to identify the significant role played by the secondary and tertiary structure of collagen-derived peptides that are involved in lipid peroxide quenching in food products. Fish collagen hydrolysate (CH) was extracted with an efficiency of 70%. The constituent peptides of CH (8.2-9.7 kDa) existed in a polyproline-II (PP-II) conformation and at a minimum concentration of 1 mg ml-1 and pH range 7 to 8, assembled into a stable, hierarchical, quasi-fibrillar (QF) network. The peroxide quenching activity of this QF-CH increased with increasing ionic stability of the assembly and decreased upon proteolytic dismantling. Upon being used as an additive, the QF-CH reduced peroxide formation by 84.5% to 98.9% in both plant and fish-based oil and increased the shelf life of soya oil by a factor of 5 after 6 months of storage. The addition of QF-CH to cultured cells quenched peroxide ions generated in situ and decreased stressor activity by a factor of 12.16 abundant peptides were identified from the CH. The reason behind the high efficacy displayed by CH was attributed to its unique charge distribution, prevalence of proton-donating amino acid residues and proximal charge delocalization by the QF network, making fish derived CH a suitable substitute for antiperoxide agents in lipid-rich food.

Fabrication of polyaniline/graphene oxide composites for implementation in humidity sensing.

This work reports the measurement of impedance variations under various humidity conditions at frequency ranges between 100 Hz and 5 MHz. An electrochemical polymerization process has been used in the synthesis including varying the mass ratios of graphene oxide (GO) in polyaniline. An electrochemical deposition method has been used to produce a sample film on an indium tin oxide glass slide. The percentage relative humidity (RH%) of the samples has been estimated to be 20-90%. Impedance and humidity had an inverse relationship, i.e. the impedance value decreased with an increase in humidity. In contrast with platinum capacitive humidity sensors (HS), the GO-based HS had a sensitivity of 75-99%, which was ~10-fold more than that of traditional sensors. With three different parameter weight % of GO, the frequency range have been 100 Hz to 5 MHz and RH% has been found to 20-90%. The HS showed a fast response and recovery time. Therefore, GO appears to be a useful material for building HS with high sensitivity for a comprehensive approach.

Electrochemical Oxidative Addition of Nucleophiles on 2-Arylindoles: Synthesis of C2-Heteroquaternary Indolin-3-ones.

An electrochemical method has been developed to synthesize 2,2-disubstituted indolin-3-ones under mild conditions. A series of nucleophiles have been added to the 2-arylindole-3-ones, generated in situ under metal-free electrochemical oxidative dearomatization of 2-arylindoles, to afford 2,2-disubstituted 3-carbonyl indoles with heteroquaternary centers in 57-79% yields.

Enantioselective Direct Synthesis of C3-Hydroxyalkylated Pyrrole via an Amine-Catalyzed Aldol/Paal-Knorr Reaction Sequence.

Creating functionality with chirality at position C3 of pyrrole is challenging. An operationally simple organocatalytic method has been developed to generate functionality with a chiral tertiary/quaternary stereocenter at position C3 of pyrrole. The process proceeds through an amine-catalyzed direct aldol reaction of succinaldehyde with various acceptor carbonyls, followed by a Paal-Knorr reaction with a primary amine in the same pot. A series of chiral C3-hydroxyalkylated N-alkyl/Ar/H-pyrroles have been synthesized for the first time with good to high yields and excellent enantioselectivity.

Fabrication of α-Fe2O3 Nanostructures: Synthesis, Characterization, and Their Promising Application in the Treatment of Carcinoma A549 Lung Cancer Cells.

In the present work, iron nanoparticles were synthesized in the α-Fe2O3 phase with the reduction of potassium hexachloroferrate(III) by using l-ascorbic acid as a reducing agent in the presence of an amphiphilic non-ionic polyethylene glycol surfactant in an aqueous solution. The synthesized α-Fe2O3 NPs were characterized by powder X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, atomic force microscopy, dynamic light scattering, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and ultraviolet-visible spectrophotometry. The powder X-ray diffraction analysis result confirmed the formation of α-Fe2O3 NPs, and the average crystallite size was found to be 45 nm. The other morphological studies suggested that α-Fe2O3 NPs were predominantly spherical in shape with a diameter ranges from 40 to 60 nm. The dynamic light scattering analysis revealed the zeta potential of α-Fe2O3 NPs as -28 ± 18 mV at maximum stability. The ultraviolet-visible spectrophotometry analysis shows an absorption peak at 394 nm, which is attributed to their surface plasmon vibration. The cytotoxicity test of synthesized α-Fe2O3 NPs was investigated against human carcinoma A549 lung cancer cells, and the biological adaptability exhibited by α-Fe2O3 NPs has opened a pathway to biomedical applications in the drug delivery system. Our investigation confirmed that l-ascorbic acid-coated α-Fe2O3 NPs with calculated IC50 ≤ 30 µg/mL are the best suited as an anticancer agent, showing the promising application in the treatment of carcinoma A549 lung cancer cells.

Catalyst-free direct regiospecific multicomponent synthesis of C3-functionalized pyrroles.

An operationally simple catalyst-free protocol for the direct regiospecific synthesis of ß-(C3)-substituted pyrroles has been developed. The enamine intermediate, in situ generated from succinaldehyde and a primary amine, was trapped with activated carbonyls before the Paal-Knorr reaction in a direct multicomponent "just-mix" fashion to furnish pyrroles with overall good yields. Several C3-substituted N-alkyl/aryl/H pyrroles have been produced under open-flask conditions with high atom economy and avoiding protection-deprotection chemistry.

Kinetic and Mechanistic Studies of the Formation of Silver Nanoparticles by Nicotinamide as a Reducing Agent.

Here, in the present study, silver nanoparticles (SNPs) in the size range 6-10 nm have been synthesized by a chemical reduction method using nicotinamide (NTA), an anti-inflammatory agent, and cetyltrimethylammonium bromide (CTAB), a good stabilizing agent, to preparing the nanoparticles in the 6-10 nm size range. Kinetic studies on the formation of SNPs have been performed spectrophotometrically at 410 nm (strong plasmon band) in aqueous medium as a function of [AgNO3], [NTA], [NaOH], and [CTAB]. The plot of ln(A ∞ - A t ) versus time exhibited a straight line and the pseudo-first-order rate constants of different variables were calculated from its slope. On the basis of experimental findings, a plausible mechanism was proposed for the formation of SNPs colloid. From the mechanism, it is proved that the reduction of silver ions proceeded through the formation of silver oxide in colloidal form by their reaction with hydroxide ions and NTA after performing their function and readily undergo hydrolysis to form nicotinic acid as a hydrolysis product with the release of ammonia gas. The preliminary characterization of the SNPs was carried out by using a UV-visible spectrophotometer. The detailed characterization of SNPs was also carried out using other experimental techniques such as Fourier transform infrared spectroscopy (FTIR), field-emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), and powder X-ray diffraction (PXRD). SNPs show a remarkable catalytic activity of up to 90% for the reduction of the cationic dye methylene blue.

Stereoselective Oxidative Mannich Reaction of Ketones with Dihydrodibenzo-Oxazepines via a Merger of Photoredox-/Electro-Catalysis with Organocatalysis.

An enantio- and diastereoselective sp3 -sp3 coupling of acyclic/cyclic ketones with dihydrodibenzo-oxazepines has been developed by merging visible light photo-redox- or electro-catalysis with organocatalysis. This approach parallelly utilizes Eosin Y or graphite electrodes for the co-catalyst-free oxidative conversion of dihydrodibenzo-oxazepines to oxazepines, followed by L-Proline catalyzed direct Mannich-type reaction with ketones. A series of enantioenriched dihydrodibenzo-oxazepines have been prepared in high yields and enantioselectivity. This method shows substantial advantages over the existing protocols by using potentially safer starting materials and cheap commercially available catalysts.

Detailed Kinetic and Mechanistic Study for the Preparation of Silver Nanoparticles by a Chemical Reduction Method in the Presence of a Neuroleptic Agent (Gabapentin) at an Alkaline pH and its Characterization.

For the very first time, a detailed kinetic study for the preparation of silver nanoparticles (silver NPs) by neuroleptic agent gabapentin (GBP) in the absence of a stabilizer has been reported in this investigation. This paper is devoted to the preparation of silver nanoparticles by a chemical reduction method in which gabapentin acts as both a reductant and a stabilizer, and AgNO3 is used as a source of Ag+ ions and NaOH for maintaining the alkaline medium. A UV-visible spectrophotometer is used to monitor the progress of the reaction kinetics in an aqueous medium by changing the concentration of different variables such as AgNO3, NaOH, and gabapentin at 40 °C. It is found that the reaction rate follows a pseudo-first-order reaction. The thermodynamic activation parameters were also studied at five different temperatures (303, 308, 313, 318, and 323 K) and used in the support of the proposed mechanistic scheme for the formation of silver nanoparticles. The prepared silver nanoparticles were characterized using different techniques: UV-visible spectrophotometry, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, and powder X-ray diffraction. The average particle size was observed in the range of 5-45 nm.

In silico and in vitro assays reveal potential inhibitors against 3CLpro main protease of SARS-CoV-2.

The COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is not showing any sign of slowing down even after the ongoing efforts of vaccination. The threats of new strains are concerning, as some of them are more infectious than the original one. A therapeutic against the disease is, therefore, of urgent need. Here, we use the DrugBank database to screen for potential inhibitors against the 3CLpro main protease of SARS-CoV-2. Instead of using the traditional approach of computational screening by docking, we developed a kernel ridge regressor (using a part of the docking data) to predict the binding energy of ligands. We used this model to screen the DrugBank database and shortlist two lead candidates (bromocriptine and avoralstat) for in vitro enzymatic study. Our results show that the 3CLpro enzyme activity in presence of 100 µM concentration of bromocriptine and avoralstat is 9.9% and 15.9%, respectively. Remarkably, bromocriptine exhibited submicromolar IC50 of 130 nM (0.13 µM). Avoralstat showed an IC50 of 2.16 µM. Further, the interactions of both drugs with 3CLpro were analyzed using molecular dynamics simulations of 100 ns. Results indicate that both ligands are stable in the binding pocket of the 3CLpro receptor. In addition, the MM-PBSA analysis revealed that bromocriptine (-29.37 kcal/mol) has a lower binding free energy compared to avoralstat (-6.91 kcal/mol). Further, hydrogen bond analysis also showed that bromocriptine interacts with the two catalytic residues, His41 and Cys145, more frequently than avoralstat.Communicated by Ramaswamy H. Sarma.

Two-pot synthesis and photophysical studies of 1,6-disubstituted 5-aza-indoles from succinaldehyde and N-aryl propargylic-imines.

A two-pot synthesis of 5-aza-indoles has been developed from aqueous succinaldehyde and N-aryl propargylic-imines. This overall protocol involves: (i) the metal-free [3 + 2] annulation of aqueous succinaldehyde and N-aryl propargylic-imines to access 2-alkynyl-pyrrole-3-aldehydes and (ii) Ag-catalyzed 6-endo-dig-cyclization to obtain substituted 5-aza-indoles in the second pot. The 5-aza-indoles showed engaging photophysical activities, and the practicality of this pot-economic gram-scale synthesis has been demonstrated.

Asymmetric Synthesis of Bridged N-Heterocycles with Tertiary Carbon Center through Barbas Dienamine-Catalysis: Scope and Applications.

A direct aza-Diels-Alder reaction between 2-aryl-3H-indolin-3-ones and cyclic-enones has been developed to access chiral indolin-3-one fused polycyclic bridged compounds. This method proceeds via proline-catalyzed Barbas-dienamine intermediate formation from various cyclic-enones such as 2-cyclopenten-1-one, 2-cyclohexene-1-one, and 2-cycloheptene-1-one, followed by a reaction with 2-aryl-3H-indol-3-ones. Several indolin-3-ones fusing [2.2.2], [2.2.1], and [3.2.1] skeletons decorated with a tertiary carbon chiral center have been prepared. Computational studies (DFT) supported the observed stereoselectivity in the method. The synthesized compounds have shown exciting photophysical activities and selective sensing of Pd2+ and Fe3+ ions through the fluorescence quenching "switch-off" mode.

Growth Kinetic Study of Tannic Acid Mediated Monodispersed Silver Nanoparticles Synthesized by Chemical Reduction Method and Its Characterization.

The complex process of nanoparticle formation in an aqueous solution is governed by kinetics and thermodynamic factors. This paper describes a room-temperature growth kinetic study and evaluation of thermodynamic activation parameters of monodispersed silver nanoparticles (AgNPs) synthesized in alkaline medium by chemical reduction method using AgNO3 as a source of Ag+ ions and tannic acid (TA) as a reductant (reducing agent) as well as a capping or stabilizing agent in the absence of any other external stabilizer. A simple and conveniently handled reaction process was monitored spectrophotometrically to study the growth kinetics in an aqueous solution as a function of the concentration of silver ion, hydroxide ion, and TA, respectively. The neutral nucleophilic group donates the electron density via a lone pair of electrons to Ag+ ions for the reduction process, i.e., for the nucleation of AgNPs colloid. Also, a few silver ions form a silver oxide, which also facilitates the nucleation center to enhance the growth of AgNPs colloid. The decrease and increase in rate constant on varying the TA concentration showed its adsorption onto the surface of metallic AgNPs and stabilized by polygalloyl units of TA and were the main elements to control the growth kinetics. Consequently, stabilized TA-mediated AgNPs are formed using the electron donated by quinone form of TA followed by a pseudo-first-order reaction. Apart from this, nanoparticles formed were characterized using UV-visible spectrophotometry, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, and powder X-ray diffraction techniques to confirm its formation during the present kinetic study.

Electrochemical Oxidative Coupling Between Benzylic C(sp3)-H and N-H of Secondary Amines: Rapid Synthesis of α-Amino α-Aryl Esters.

An intermolecular electrochemical coupling between the benzylic C(sp3)-H bond and various secondary amines is reported. The electronic behavior of two electronically rich units viz the α-position of α-aryl acetates and amines was engineered electrochemically, thus facilitating their reactivity for the direct access of α-amino esters. A series of acyclic/cyclic secondary amines and α-aryl acetates were tested to furnish the corresponding α-amino esters with high yields (up to 92%) under mild conditions.

Direct catalytic synthesis of ß-(C3)-substituted pyrroles: a complementary addition to the Paal-Knorr reaction.

The synthesis of ß-(C3)-functionalized pyrroles is a challenging task and requires a multistep protocol. An operationally simple direct catalytic synthesis of ß-substituted pyrroles has been developed. This one-pot multicomponent method combined aqueous succinaldehyde as 1,4-dicarbonyl, primary amines, and isatins to access hydroxyl-oxindole ß-tethered pyrroles. Direct synthesis of the ß-substituted free NH-pyrrole is the central intensity of this work. DFT-calculations and preliminary mechanism investigation support the possible reaction pathway.

Real-Time Molecular Monitoring in Acute Myeloid Leukemia With Circulating Tumor DNA.

The clonal evolution of acute myeloid leukemia (AML), an oligoclonal hematological malignancy, is driven by a plethora of cytogenetic abnormalities, gene mutations, abnormal epigenetic patterns, and aberrant gene expressions. These alterations in the leukemic blasts promote clinically diverse manifestations with common characteristics of high relapse and drug resistance. Defining and real-time monitoring of a personalized panel of these predictive genetic biomarkers is rapidly being adapted in clinical setting for diagnostic, prognostic, and therapeutic decision-making in AML. A major challenge remains the frequency of invasive biopsy procedures that can be routinely performed for monitoring of AML disease progression. Moreover, a single-site biopsy is not representative of the tumor heterogeneity as it is spatially and temporally constrained and necessitates the understanding of longitudinal and spatial subclonal dynamics in AML. Hematopoietic cells are a major contributor to plasma cell-free DNA, which also contain leukemia-specific aberrations as the circulating tumor-derived DNA (ctDNA) fraction. Plasma cell-free DNA analysis holds immense potential as a minimally invasive tool for genomic profiling at diagnosis as well as clonal evolution during AML disease progression. With the technological advances and increasing sensitivity for detection of ctDNA, both genetic and epigenetic aberrations can be qualitatively and quantitatively evaluated. However, challenges remain in validating the utility of liquid biopsy tools in clinics, and universal recommendations are still awaited towards reliable diagnostics and prognostics. Here, we provide an overview on the scope of ctDNA analyses for prognosis, assessment of response to treatment and measurable residual disease, prediction of disease relapse, development of acquired resistance and beyond in AML.

Direct Amine-Catalyzed Enantioselective Synthesis of Pentacyclic Dibenzo[b,f][1,4]oxazepine/Thiazepine-Fused Isoquinuclidines along with DFT Calculations.

A direct protocol for the asymmetric synthesis of dibenzoxazepine/thiazepine-fused [2.2.2] isoquinuclidines is developed. The reaction proceeds through a proline-catalyzed direct Mannich reaction followed by an intramolecular aza-Michael cascade sequence between 2-cyclohexene-1-one and various tricyclic imines, like dibenzoxazepines/thiazepines, as an overall [4 + 2] aza-Diels-Alder reaction. A series of pentacyclic isoquinuclidines have been prepared, with complete endo-selectivity, in good to high yields and excellent enantioselectivity (>99:1). Density functional theory (DFT) calculations further support the observed high stereochemical outcome of the reaction.