2-Pyridone-Directed CuII-Catalyzed General Method of C(sp2)-H Activation for C-S, C-Se, and C-N Cross-Coupling: Easy Access to Aryl Thioethers, Selenide Ethers, and Sulfonamides and DFT Study.

We have demonstrated N-substituted 2-pyridones as an N,O-directing group for selective C(sp2)-H-activated thiolation, selenylation, and sulfonamidation of ortho C-H bonds of benzamides. This method utilizes a cost-effective Cu(II)-salt catalyst instead of precious metal catalysts, achieving high yields, including gram-scale synthesis and excellent functional group tolerance. We applied this protocol to access 30 different compounds with high yields, demonstrating thiolation of fluorine-substituted benzamides as well. Density functional theory (DFT) calculations support the mechanism, including acetate-supported concerted metalation deprotonation (CMD) steps and the unique role of dimethyl sulfoxide (DMSO) solvent. The facile synthesis of pharmaceutically important sulfonamides and other compounds highlights the method's potential in chemistry and medicinal chemistry.

Ceria-Graphene Oxide Nanocomposite for Electro-oxidation of Urea: An Experimental and Theoretical Investigation.

This study explores the potential of ceria-graphene oxide (CeO2-GO) nanocomposites as efficient electrocatalysts for urea electro-oxidation (UOR). This work combines experimental and theoretical investigations and characterization techniques confirm the successful formation of the CeO2 embedded on graphene oxide sheets. UOR activity was found to be dependent on both OH- and urea concentrations. The optimal UOR performance was achieved in a 0.1 M urea and 1.0 M KOH solution, as evidenced by the low Tafel slope of 60 mV/dec and high turnover frequency (TOF) of 1.690 s-1. DFT calculations revealed that the CeO2-GO nanocomposite exhibited strong urea adsorption due to its favorable bond lengths (Ce-O: 2.58 Å, O-H: 1.77 Å) and high adsorption energy (-1.05 eV). These findings revealed that the CeO2-GO nanocomposites are promising as efficient and durable electrocatalysts for urea conversion to valuable products like nitrogen and hydrogen gas, with potential applications in clean energy generation and ammonia synthesis.

New routes towards azomethine ylide generation from prolines to synthesize diverse N-heterocycles: a DFT supported endo-selective mechanism.

Azomethine ylides are generated using either organocatalysts or metal catalysts via a ballet of decarboxylative C-N coupling choreographed by prolines. These strategies enable diastereoselective [3 + 2] cycloaddition, C-C coupling, and ring annulation, providing sustainable routes. The synthesized pyrrolizines and other heterocycles have potential applications in the development of crucial biomolecules and pharmaceuticals. The endoselectivity of the azomethine ylide is realized and supported through DFT calculations.

A benzimidazole-based Cu(II) complex catalyzed site-selective C-H sulfenylation of imidazo-[1,2-a]pyridines using CS2 as a sulfur source.

A new benzimidazole-based Cu(II) complex catalyzed site-selective sulfenylation of imidazo[1,2-a]pyridines with benzyl/alkyl/allyl bromides and CS2 at 100 °C in DMF : H2O is reported. The present methodology has been developed for the synthesis of 3-sulfenyl imidazo[1,2-a]pyridines in good yields with a broad substrate scope. In this protocol, CS2, commonly known as a non-polar small molecule bioregulator (SMB), is converted to valuable sulfenylated imidazo[1,2-a]pyridine derivatives. In addition, theoretical investigations along with experimental evidence unfold the insights into the probable mechanistic pathway of site-selective sulfenylation from S,S-dibenzyltrithiocarbonate, which is particularly formed as an intermediate during the reaction.

Synthesis of Intrinsically-Fluorescent Aliphatic Tautomeric Polymers for Proton-Conductivity, Dual-State Emission, and Sensing/Oxidation-Reduction of Metal Ions.

Herein, fluorescent conducting tautomeric polymers (FCTPs) are developed by polymerizing 2-methylprop-2-enoic acid (MPEA), methyl-2-methylpropenoate (MMP), N-(propan-2-yl)prop-2-enamide (PPE), and in situ-anchored 3-(N-(propan-2-yl)prop-2-enamido)-2-methylpropanoic acid (PPEMPA). Among as-synthesized FCTPs, the most promising characteristics in FCTP3 are confirmed by NMR and Fourier transform infrared (FTIR) spectroscopies, luminescence enhancements, and computational studies. In FCTP3, ─C(═O)NH─, -C(═O)N<, ─C(═O)OH, and ─C(═O)OCH3 subluminophores are identified by theoretical calculations and experimental analyses. These subluminophores facilitate redox characteristics, solid state emissions, aggregation-enhanced emissions (AEEs), excited-state intramolecular proton transfer (ESIPT), and conductivities in FCTP3. The ESIPT-associated dual emission/AEEs of FCTP3 are elucidated by time correlated single photon counting (TCSPC) investigation, solvent polarity effects, concentration-dependent emissions, dynamic light scattering (DLS) measurements, field emission scanning electron microscopy images, and computational calculations. The cyclic voltammetry measurements of FCTP3 indicate cumulative redox efficacy of ─C(═O)OH, ─C(═O)NH─/-C(═O)N<, ─C(─O─)═NH+─/─C(─O─)═N+, and ─C(═N)OH functionalities. In FCTP3, ESIPT-associated dual-emission enable in the selective detection of Cr(III)/Cu(II) at λem1/λem2 with the limit of detection of 0.0343/0.079 ppb. The preferential interaction of Cr(III)/Cu(II) with FCTP3 (amide)/FCTP3 (imidol) and oxidation/reduction of Cr(III)/Cu(II) to Cr(VI)/Cu(I) are further supported by NMR-titration; FTIR and X-ray photoelectron spectroscopy analyses; TCSPC/electrochemical/DLS measurement; alongside theoretical calculations. The proton conductivity of FCTP3 is explored by electrochemical impedance spectroscopy and I-V measurements.

Concentration- and Solvent-Induced Chiral Tuning by Manipulating Non-Proteinogenic Amino Acids in Glycoconjugate Supra-Scaffolds: Interaction with Protein, and Streptomycin Delivery.

We showed solvent- and concentration-triggered chiral tuning of the fibrous assemblies of two novel glycoconjugates Z-P(Gly)-Glu and Z-F(4-N)-Glu made by chemical attachment of Cbz-protected [short as Z)] non-proteinogenic amino acids L-phenylglycine [short as P(Gly)] and 4-Nitro-L-phenylalanine [short as F(4-N)] with D-glucosamine [short as Glu]. Both biomimetic gelators can form self-healing and shape-persistent gels with a very low critical gelator concentration in water as well as in various organic solvents, indicating they are ambidextrous supergelators. Detailed spectroscopic studies suggested ß-sheet secondary structure formation during anisotropic self-aggregation of the gelators which resulted in the formation of hierarchical left-handed helical fibers in acetone with an interlayer spacing of 2.4 nm. After the physical characterization of the gels, serum protein interaction with the gelators was assessed, indicating they may be ideal for biomedical applications. Further, both gelators are benign, non-immunogenic, non-allergenic, and non-toxic in nature, which was confirmed by performing the blood parameters and liver function tests on Wister rats. Streptomycin-loaded hydrogels showed efficacious antibacterial activity in vitro and in vivo as well. Finally, cell attachment and biocompatibility of the hydrogels were demonstrated which opens a newer avenue for promising biomedical and therapeutic applications.

CuII-Catalyzed cis-Selective Synthesis of Ketoepoxides from Phenacyl Bromides and Water.

A verity of α,ß-ketoepoxides was synthesized using a CuII-catalyzed oxidative C-C/O-C coupled cyclization strategy with high yield and cis-selectivity. Water is used as the source of oxygen and phenacyl bromide as the carbon in the valuable epoxides. The self-coupling method was extended to cross-coupling between phenacyl bromides with benzyl bromides. A high cis-diastereoselectivity was observed in all the synthesized ketoepoxides. Control experiments and density functional theory (DFT) study were performed to understand the CuII-CuI transition mechanism.

Designed and synthesizedde novoANTPABA-PDI nanomaterial as an acceptor in inverted solar cell at ambient atmosphere.

In this work, a novel soluble and air-stable electron acceptor containing perylenediimide moiety named ANTPABA-PDI was designed and synthesized with band gap 1.78eV and that was used as non-fullerene acceptor material. ANTPABA-PDI possess not only good solubility but also much lower LUMO (lowest unoccupied molecular orbital) energy level. Furthermore, its excellent electron acceptor capability also supported by density functional theory calculation which validates the experimental observations. Inverted organic solar cell has been fabricated using ANTPABA-PDI along with P3HT as standard donor material in ambient atmosphere. The device, after characterization in open air, exhibited a power conversion efficiency of 1.70%. This is the first ever PDI based organic solar cell that has been fabricated completely in ambient atmosphere. The characterizations of the device have also been performed in ambient atmosphere. This kind of stable organic material can easily be used in fabricating organic solar cell and therefore it can be used as the best alternative as non-fullerene acceptor materials.

Repurposing of anti-lung cancer drugs as multi-target inhibitors of SARS-CoV-2 proteins: An insight from molecular docking and MD-simulation study.

Herein we have selected seventeen anti-lung cancer drugs to screen against Mpro, PLpro and spike glycoproteins of SARS-CoV-2to ascertain the potential therapeutic agent against COVID-19. ADMET profiling were employed to evaluate their pharmacokinetic properties. Molecular docking studies revealed that Capmatinib (CAP) showed highest binding affinity against the selected proteins of SARS-CoV-2. Molecular Dynamics (MD) simulation and the analysis of RMSD, RMSF, and binding energy confirmed the abrupt conformational changes of the proteins due to the presence of this drug. These findings provide an opportunity for doing advanced experimental research to evaluate the potential drug to combat COVID-19.

Solvent- and Substrate-Induced Chiroptical Inversion in Amphiphilic, Biocompatible Glycoconjugate Supramolecules: Shape-Persistent Gelation, Self-Healing, and Antibacterial Activity.

We have shown solvent- and substrate-dependent chiral inversion of a few glycoconjugate supramolecules. (Z)-F-Gluco, in which d-glucosamine has been attached chemically to Cbz-protected l-phenylalanine at the C terminus, forms a self-healing hydrogel through intertwining of the nanofibers wherein the gelators undergo lamellar packing in the ß-sheet secondary structures with a single chiral handedness. Dihybrid (Z)-F-gluco nanocomposite gel was prepared by in-situ formation of silver nanoparticles AgNPs in the gel; this enhances the mechanical properties of the composite gel through physical crosslinking without altering the packing pattern. In contrast, (Z)-L-gluco bearing an l-leucine moiety does not form a hydrogel but an organogel. Interestingly, the chiral handedness of the aggregates of (Z)-L-gluco can be reversed by choosing suitable solvents. In addition to self-healing behavior, (Z)-L-gluco gel revealed shape persistency. Further, (Z)-F-gluco hydrogel is benign, nontoxic, non-immunogenic, and non-allergenic in animal cells. AgNP-loaded (Z)-F-gluco hydrogel showed antibacterial activity against both Gram-positive and Gram-negative bacteria.

Encapsulated hydroxychloroquine and chloroquine into cyclic oligosaccharides are the potential therapeutics for COVID-19: insights from first-principles calculations.

Novel-Coronavirus (COVID-19) outburst has become a worldwide pandemic which threaten the scientific community to design and discover efficient and effective treatment strategies against this deadly virus (SARS-CoV-2). Still now, there is no antiviral therapy or drug available in the market which can efficiently combat the infection caused by this virus. In this respect, using available drugs by screening with molecular docking and molecular dynamics studies not only minimizes lengthy chemical trials but also reduces discovery cost for the pharmaceutical industry. During the COVID-19 pandemic situations hydroxychloroquine, chloroquine known as HCQ and CQ tablets have gained popularity as for the treatment coronavirus (COVID-19) but the main threatening effect of HCQ, CQ use lies on their side effects like blistering, peeling, loosening of the skin, blurred vision stomach pain, diarrhea, chest discomfort, pain, or tightness, cough or hoarseness which require immediate medical attention. Encapsulation of HCQ and CQ drugs by the cyclic macromolecules such as α and ß-Cyclodextrin, to form host-guest complexes is very effective strategy to mask the cytotoxicity of certain drugs and alleviating and modulating side effects of drug applications. In the present work, we have encapsulated the HCQ and CQ drugs α and ß-Cyclodextrin and made a comprehensive analysis of stability, optical properties. Details analysis verified that between QC and HCQ, HQC showed stronger affinity towards ß-Cyclodextrin. This strategy can reduce the side effect of HCQ and CQ thereby offers a new way to use these drugs. We hope the present study should help the researchers to develop potential therapeutics against the novel coronavirus.

Inhibitory effect of compounds extracted from Monochoria hastata (L.) Solms on SARS-CoV-2 main protease: An insight from molecular docking and MD-simulation studies.

Using molecular docking and other studies, 20 compounds extracted from Monochoria hastata (L.) Solms were screened, and their inhibitory efficiency examined against main protease (3CLpro) of SARS CoV-2. All the compounds were found to binding with 3CLpro through van der Waals and electrostatic forces of attractions. Among them, Azelaic dihydrazide (ADZ) was found to have the highest docking score. 3CLpro-ADZ complex was studied by MD simulation. ADZ was found to disrupt the structure of 3CLpro after 2 ns. RMSD and RMSF analysis along with sequence and binding energy analysis suggest that ADZ can be a potential drug against SARS CoV-2.

Inhibitory efficiency of potential drugs against SARS-CoV-2 by blocking human angiotensin converting enzyme-2: Virtual screening and molecular dynamics study.

Till date millions of people are infected by SARS-CoV-2 throughout the world, while no potential therapeutics or vaccines are available to combat this deadly virus. Blocking of human angiotensin-converting enzyme 2 (ACE-2) receptor, the binding site of SARS-CoV-2 spike protein, an effective strategy to discover a drug for COVID-19. Herein we have selected 24 anti-bacterial and anti-viral drugs and made a comprehensive analysis by screened them virtually against ACE-2 receptor to find the best blocker by molecular docking and molecular dynamics studies. Analysis of results revealed that, Cefpiramide (CPM) showed the highest binding affinity of -9.1 kcal/mol. Furthermore, MD study for 10 ns and evaluation of parameters like RMSD, RMSF, radius of gyration, solvent accessible surface area analysis confirmed that CPM effectively binds and blocks ACE-2 receptor efficiently.

Nonconjugated Biocompatible Macromolecular Luminogens for Sensing and Removals of Fe(III) and Cu(II): DFT Studies on Selective Coordination(s) and On-Off Sensing.

This work reports the design and synthesis of two nonaromatic biocompatible macromolecular luminogens, i.e., 2-(dimethylamino)ethyl methacrylate-co-2-(dimethylamino)ethyl 3-(N-(methylol)acrylamido)-2-methylpropanoate-co-N-(methylol)acrylamide/DMAEMA-co-DMAENMAMP-co-NMA (P1) and methacrylic acid-co-3-(N-(methylol)acrylamido)-2-methylpropanoic acid-co-N-(methylol)acrylamide/MEA-co-NMAMPA-co-NMA (P2), prepared through in situ anchored acrylamido-ester/DMAENMAMP and acrylamido-acid/NMAMPA third comonomers, respectively, in a facile polymerization of two non-luminous monomers in water medium to circumvent the drawbacks related to aggregation-caused quenching of aromatic luminogens. The structures of P1/P2, in situ anchored comonomers, fluorophores, N-branching associated n-π* interactions, and hydrogen bonding assisted aggregation-enhanced emissions are comprehended by nuclear magnetic resonance, Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), ultraviolet-visible, thermogravimetric analysis (TGA), dynamic light scattering (DLS), transmission electron microscopy (TEM), fluorescence lifetime, and fluorescence imaging. P1 and P2 are appropriate for sensitive detections/exclusions of Fe(III)/Cu(II) and cell-imaging. The intrinsic fluorescence, on-off sensing, selective coordinations of Fe(III) and Cu(II) with fluorophores, emission quenching mechanisms, and removals of Fe(III) and Cu(II) are investigated by DFT/NTO analyses of P1/P2 and Fe(III)-P1 and Cu(II)-P2 complexes, XPS, and isotherms and kinetics parameters. The excellent biocompatibilities, comparable limit of detections, i.e., 1.70 × 10-7 and 1.59 × 10-7 [m], and higher adsorption capacities, i.e., 77.25 and 154.13 mg g-1 , at low ppm; 303 K; and pH = 7 compel P1/P2 to be acceptable for multipurpose applications.

Inhibitory capacity of chloroquine against SARS-COV-2 by effective binding with angiotensin converting enzyme-2 receptor: An insight from molecular docking and MD-simulation studies.

The main binding site for SARS-COV-2 spike protein in human body is human Angiotensin converting enzyme 2 (ACE2) protein receptor. Herein we present the effect of chloroquine (CLQ) on human ACE2 receptor. Molecular docking studies showed that chloroquine have a docking score is quite high compare to other well known drugs. Furthermore, molecular dynamics (MD) studies with CLQ docked ACE2 results in large fluctuations on RMSD up to 2.3 ns, indicating conformational and rotational changes due to the presence of drug molecule in the ACE2 moiety. Analysis of results showed that CLQ can effect the conformation of human ACE2 receptor. We believed that this work will help researchers to understand better the effect of CLQ on ACE2.

Screening of potential drug from Azadirachta Indica (Neem) extracts for SARS-CoV-2: An insight from molecular docking and MD-simulation studies.

Azadirachta Indica (Neem) extracts have been known for their anti-bacterial and other effects since ancient times. The present work examines the inhibitory activity of Neem extracts on Papain like protease (PLpro) of the novel coronavirus SARS-CoV-2. The activity is analysed by molecular docking study along with molecular dynamics simulation. All the studied Neem compounds showed decent level of inhibitory activity against PLpro of SARS-CoV-2. Among them, desacetylgedunin (DCG) found in Neem seed showed the highest binding affinity towards PLpro. Furthermore, MD-simulation studies supported by standard analysis (e.g. root mean square deviation and fluctuation (RMSD, RMSF), radius of gyration, solvent accessible surface area (SASA)) showed large impact on the structure of PLpro by DCG. We believe that the significant effect of DCG on PLpro may help in therapeutic efforts against SARS-CoV-2.

Inhibitory efficacy of RNA virus drugs against SARS-CoV-2 proteins: An extensive study.

Herein we have made a comprehensive analysis of inhibitory efficacy of 16 RNA virus drugs against RdRp, Mpro and PLpro proteins of SARS-CoV-2. Analysis of docked conformation revealed that Baloxavir marboxil (BMX) corresponds to the highest binding energy. Analysis of residue confirmed that BMX strongly interact with these three proteins involving H-bonding, ionic as well as hydrophobic interactions. Molecular dynamics simulation and analysis of parameters like RMSD, RMSF, binding energy confirmed noticeable conformational alternation with these proteins with makeable effect on RdRp. The potentially inhibitory action of BMX against these three proteins suggests the inhibition of overall transcription process of SARS-CoV-2. These observation along with the recently observed inhibitory action of BMX on influenza with clinically proven no side effects emphasizes to uncover the role of BMX by in-vitro and in-vivo analysis.

One-pot synthesis of sodium alginate-grafted-terpolymer hydrogel for As(III) and V(V) removal: In situ anchored comonomer and DFT studies on structures.

In this work, an optimum sodium alginate (NaAlg)-grafted-[sodium 2-methylenesuccinate-co-sodium 2-((2-(isobutyryloxy)ethoxy)methyl)succinate-co-ethylene glycol methacrylate, i.e., SMS-co-SIBEMS-co-EGMA, i.e., P1], i.e., P2, was selected among twelve hydrogels synthesized by employing variable amounts of synthesis parameters through a facile polymerization of SMS and EGMA monomers. In P1 and P2, SIBEMS third comonomer was strategically anchored in situ. The formation of terpolymer, i.e., P1, rather than generally expected copolymer, i.e., SMS-co-EGMA/ CoP1, was explored via closeness of experimental and simulated excitation energies of P1 and CoP1, measured by using density functional theory (DFT). The grafting of NaAlg into synthetic P1 elevated swelling, crosslink density (CD), network stability, reusability, and adsorption capacity (AC) of semisynthetic hydrogel, i.e., P2. The reusable P2 presenting optimum result among swelling, CD, and mean molar mass was chosen selectively for removals of As(III) and V(V). The structures of P1, P2, and adsorbed P2, i.e., As(III)-P2 and V(V)-P2; NaAlg-grafting; in situ anchored SIBEMS comonomer; reusability; thermostability; and surface properties were explored through XPS-NMR-FTIR-UV-vis, DFT, TG, DLS, XRD, SEM, pHPZC, and network and thermodynamic energies. The ACs of 0.025 g P2 for As(III) and V(V) were 112.24 and 88.89 mg g-1, respectively, at 308 K and within 5-100 mg L-1. The ACs reduced to 67.26, 75.49, 71.42, and 98.25 mg g-1 for As(III) and 40.25, 50.49, 45.37, and 67.88 mg g-1 for V(V) in the presence of Mn(II), Cu(II), Ni(II), and Zn(II), respectively.

Complementary amide-based donor-acceptor with unique nano-scale aggregation, fluorescence, and band gap-lowering properties: a WORM memory device.

Organic fluorescent semiconducting nanomaterials have gained widespread research interest owing to their potential applications in the arena of high-tech devices. We designed two pyrazaacene-based compounds, their stacked system, and the role of gluing interactions to fabricate nanomaterials, and determined the prospective band gaps utilizing the density functional theory calculation. The two pyrazaacene derivatives containing complementary amide linkages (-CONH and -NHCO) were efficiently synthesized. The synthesized compounds are highly soluble in common organic solvents as well as highly fluorescent and photostable. The heterocycles and their mixture displayed efficient solvent dependent fluorescence in the visible region of the solar spectrum. Notably, the compounds were associated through complementary NH•••O = C type hydrogen bonding, π-π stacking, and hydrophobic interactions, and thereby afforded nanomaterials with a low band gap. Fascinatingly, the fabricated stacked nanomaterial system exhibited resistive switching behavior, leading to the fabrication of an efficient write-once-read-many-times memory device of crossbar structure.

Inhibitory activity of hydroxychloroquine on COVID-19 main protease: An insight from MD-simulation studies.

The present work is an investigation to test hydroxychloroquine as an inhibitor for the COVID-19 main protease. Molecular docking studies revealed a high docking score and interaction energies and decent level of docking within the cavity in protease moiety. Molecular dynamics simulations also lead to the evaluation of conformational energies, average H-bonding distance, RMSD plots etc. Large RMSD fluctuations for the first 2 ns seem to provide the conformational and rotational changes associated with the drug molecule when it comes into the vicinity on the protease matrix. Snapshots of structural changes with respect to time vividly indicates that drug molecule has a profound impact on the binding sites as well as overall geometry of the protease moiety. On the whole, hydroxyxhloroquine confers good inhibitory response to COVID-19 main protease. We hope the present study should help workers in the field to develop potential vaccines and therapeutics against the novel coronavirus.