Room-Temperature Synthesis of Biogenic δ-MnO2 NPs for the Dehydrogenative Coupling of Diamines with Alcohols for Benzimidazole and Quinoxaline Synthesis: An Efficient Catalyst for Electrochemical Applications.

An efficient, unique, and eco-friendly biogenic synthesis of single-crystalline δ-phase manganese oxide nanoparticles (MnO2 NPs) using Gliricidia sepium leaves (GSL) extract at room temperature has been revealed for the first time. The active chemicals present in the GSL extract were found to serve as both reducing and stabilizing agents. The catalyst shows an excellent surface area of 301.13 m2 g-1, a mean pore diameter of 4.01 nm, and 39.97% w/w of active metal content. The reactivity of the synthesized catalyst was demonstrated by achieving a one-pot synthesis of benzimidazoles and quinoxalines via an acceptorless dehydrogenative coupling strategy utilizing biorenewable alcohols. The release of hydrogen gas was observed as the only side product and proven by its successful utilization for alkene reduction which supports the mechanistic elucidation. The release of hydrogen gas as a useful byproduct highlights the scientific importance of the present methodology. Additionally, gram-scale synthesis and catalyst recyclability studies are deliberated. Importantly, the δ-MnO2 NP catalyst exhibited superior catalytic activity and high durability toward hydrogen evolution reaction in alkaline media, highlighting the dual use of the catalyst. The δ-MnO2 NPs attain the current density of 10 mA/cm2 at an overpotential of 154 mV with a Tafel slope of 119 mV/dec.

Reusable nano-catalyzed green protocols for the synthesis of quinoxalines: an overview.

Heterocyclic compounds are very widely distributed in nature and are essential for life activities. They play a vital role in the metabolism of all living cells, for example, vitamins and co-enzyme precursors thiamine, riboflavin etc. Quinoxalines are a class of N-heterocycles that are present in a variety of natural and synthetic compounds. The distinct pharmacological activities of quinoxalines have attracted medicinal chemists considerably over the past few decades. Quinoxaline-based compounds possess extensive potential applications as medicinal drugs, presently; more than fifteen drugs are available for the treatment of different diseases. Diverse synthetic protocols have been developed via a one-pot approach using efficient catalysts, reagents, and nano-composites/nanocatalysts etc. But the use of homogeneous and transition metal-based catalysts suffers some demerits such as low atom economy, recovery of catalysts, harsh reaction conditions, extended reaction period, expensive catalysts, the formation of by-products, and unsatisfactory yield of products as well as toxic solvents. These drawbacks have shifted the attention of chemists/researchers to develop green and efficient protocols for synthesizing quinoxaline derivatives. In this context, many efficient methods have been developed for the synthesis of quinoxalines using nanocatalysts or nanostructures. In this review, we have summarized the recent progress (till 2023) in the nano-catalyzed synthesis of quinoxalines using condensation of o-phenylenediamine with diketone/other reagents with plausible mechanistic details. With this review, we hope that some more efficient ways of synthesizing quinoxalines can be developed by synthetic chemists.

Tuning the Surface Functionality of Fe3O4 for Sensitive and Selective Detection of Heavy Metal Ions.

The functionalization of materials for ultrasensitive detection of heavy metal ions (HMIs) in the environment is crucial. Herewith, we have functionalized inexpensive and environmentally friendly Fe3O4 nanoparticles with D-valine (Fe3O4-D-Val) by a simple co-precipitation synthetic approach characterized by XRD, FE-SEM, and FTIR spectroscopy. The Fe3O4-D-Val sensor was used for the ultrasensitive detection of Cd+2, Pb+2, and Cu+2 in water samples. This sensor shows a very low detection limit of 11.29, 4.59, and 20.07 nM for Cd+2, Pb+2, and Cu+2, respectively. The detection limits are much lower than the values suggested by the world health Organization. The real water samples were also analyzed using the developed sensor.

Aqueous, Non-Polymer-Based Perovskite Quantum Dots for Bioimaging: Conserving Fluorescence and Long-Term Stability via Simple and Robust Synthesis.

Perovskite quantum dots (PQDs) offer high photoluminescence quantum yields; however, due to their limited stability in aqueous media, to date their utilization in biomedical applications has been limited. The present work demonstrates highly fluorescent and stable aqueous PQDs that were synthesized using a facile engineered phase transfer method. Ligands were engineered to have a dual functionality, i.e., they could simultaneously mediate the strong binding of PQDs and the interactions with water molecules. The resultant water-soluble PQDs demonstrated robust structural and optical properties. The extracted aqueous PQDs remained stable in pellet form for 8 months, which was the entire test duration. Notably, 100% of their fluorescence was also retained. As a proof-of-concept experiment, the water-soluble PQDs were successfully tagged to polyclonal antibodies and used to image Escherichia coli cells in aqueous media. No structural or optical disturbance in PQDs was detected throughout the process. This work marks the beginning of the use of nonpolymeric aqueous PQDs and shows their strong potential to be used in biological applications.

Synthetic and natural coumarins as potent anticonvulsant agents: A review with structure-activity relationship.

WHAT IS KNOWN AND OBJECTIVE: The main objective of this review is to highlight the most relevant studies since 1990 (to date) in the area of medicinal chemistry aspects to provide a panoramic view to the biologists/medicinal chemists working in this area and would assist them in their efforts to design, synthesize and extract (from natural source) coumarin-based anticonvulsant agents. Also, the structure-activity relationship (SAR) studies are also discussed for further rational design of this kind of derivatives. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic coumarin-based antiepileptic agents. METHODS: A literature review emphasizing the application of coumarin core as antiepileptic agents identify articles related to the topic; we performed a standardized search from 1990 to November 2021, using search engines like Scifinder, web of Science, Pubmed and Scopus. RESULTS AND DISCUSSION: This review gives an overview of attempts to shed light and compile published reports on coumarin derivatives along with some opinions on different approaches to help the medicinal chemists in designing future generation potent yet safer anticonvulsant agents. The possible structure-activity relationships (SARs) will also be discussed to indicate the direction for the rational design of more effective candidates. WHAT IS NEW AND CONCLUSION: The findings from this review provide new indications or directions for the discovery of new and better drugs from synthetic and naturally occurring coumarins as antiepileptic agents. In our review, we have tried to depict the recent researches which made in the design and development of novel anticonvulsant compounds with coumarin nucleus. Also, SAR of expressed derivatives indicated that the choice of a fitting substitution containing electron-withdrawing/donating groups to coumarin or with some heterocyclic moieties joined to parent coumarin skeleton assumes an essential role in changing the anticonvulsant activity of synthesized derivatives. These findings encourage the scientific community towards the optimization of the pharmacological profile of this structural moiety as an important scaffold for the treatment of epilepsy.

Glucose oxidase mimicking half-sandwich nickel(II) complexes of coumarin substituted N-heterocyclic carbenes as novel molecular electrocatalysts for ultrasensitive and selective determination of glucose.

Glucose oxidase mimicking nickel-based porous structures with organic anchors are developed as cheap and reliable electrochemical sensors for the quantitative detection of glucose. A series of sterically and electronically modulated, air- and moisture-stable half-sandwich nickel(II) NHC complexes were prepared and characterized. Under the optimized electrocatalytic conditions, the nickel complex immobilized glassy carbon electrodes (GCEs) displayed high sensitivity (0.663, 1.280, 1.990 and 0.182 µA/µM) towards glucose detection, which is much higher than that of 3D porous nickel networks. The limit of detection of modified GCEs is found in the range 1.56-2.09 µM with much wider linear sensing range, and having a catalytic rate constant of 0.273 × 103 M-1s-1. Finally, the selectivity of the modified GCEs towards glucose in presence of other blood constituents was also evaluated.

Quinoxaline and quinoxaline-1,4-di-N-oxides: An emerging class of antimycobacterials.

Tuberculosis (TB) is a highly dreaded, infectious, chronic, airborne disease affecting more than two million people all around the world, with more than eight million cases every calendar year. TB is the second leading infectious cause of death after HIV/AIDS. Over the past few decades, numerous efforts have been undertaken to develop new anti-TB agents. The current frontline therapy for TB consists of administering three or more different drugs (usually isoniazid, rifampin, pyrazinamide, and ethambutol) over an extended period of time. But these drugs will take 6-12 months to cure TB, along with many side effects; hence, there is an urgent need to explore new anti-TB agents. Quinoxaline derivatives are a class of compounds that show a spectrum of biological properties and the interest in these compounds is exponentially growing within the field of medicinal chemistry. Quinoxaline-1,4-di-N-oxide derivatives have shown to improve the biological results and are endowed with anti-viral, anti-cancer, anti-bacterial, and anti-protozoal activities with application in many other therapeutic areas. Since quinoxaline derivatives are regarded as a new class of effective anti-TB candidates, their 1,4-di-N-oxide analogues may show promising in vitro and in vivo anti-TB activities and might be able to prevent the drug resistance to a certain extent. Therefore, the main aim of this review is to focus on important quinoxaline and quinoxaline-1,4-di-N-oxide analogues that have shown anti-TB activities, and their structure-activity relationships for designing anti-TB agents with better efficacies. The present review will be helpful in providing insights for rational designs of more active and less toxic quinoxaline-based anti-TB prodrugs.

Sterically modulated silver(I) complexes of coumarin substituted benzimidazol-2-ylidenes: Synthesis, crystal structures and evaluation of their antimicrobial and antilung cancer potentials.

In this contribution, a series of sterically-encumbered coumarin substituted benzimidazole-based N-heterocyclic carbene (NHC) precursors (1-12) and their silver(I)-NHC complexes (13-24) are reported. Molecular structure of NHC precursors 8 and 12 and cationic complexes 15 and 16 was established by single crystal X-ray diffraction method. The silver(I) complexes demonstrated various significant intramolecular agostic-like interactions operating between the metal center and the hydrogen atoms of the substituents alongside a variety of feeble π-π stacking interactions. A distorted linear coordination geometry is documented at the silver(I) center with the anti-arrangement of the ligands. Further, the complexes demonstrated promising antibacterial properties against Gram positive and Gram negative bacterial strains, especially complex 18 displayed a minimum inhibitory concentration (MIC) of 2 and 4 µg/mL against S. aureus and E. coli, and P. aeruginosa, respectively. Furthermore, complexes 14, 15, 16 and 18 were found cytotoxic against the human lung cancer cell lines A549 and H1975 with the IC50 (concentration of the test sample required to kill 50% of the cell population) value under 10 µM, while mono-NHC complex 20 displayed a potential drug window with the IC50 of 13.7 ±â€¯2.70 and 14.5 ±â€¯1.20 µM against the cancer cell lines H1975 and A549, respectively. Notably, these complexes displayed relatively lesser cytotoxic behaviour against the normal skin fibroblast cell line, Hs68. All the NHC precursors displayed significantly lower biological activities compared with their respective complexes, indicating the utility of silver(I) ions in antimicrobial and antilung cancer applications.

An overview of benzo[b]thiophene-based medicinal chemistry.

Among sulfur containing heterocycles, benzothiophene and its derivatives are at the focus as these candidates have structural similarities with active compounds to develop new potent lead molecules in drug design. Benzo[b]thiophene scaffold is one of the privileged structures in drug discovery as this core exhibits various biological activities allowing them to act as anti-microbial, anti-cancer, anti-inflammatory, anti-oxidant, anti-tubercular, anti-diabetic, anti-convulsant agents and many more. Further, numerous benzothiophene-based compounds as clinical drugs have been extensively used to treat various types of diseases with high therapeutic potency, which has led to their extensive developments. Due to the wide range of biological activities of benzothiophene, their structure activity relationships (SAR) have generated interest among medicinal chemists, and this has culminated in the discovery of several lead molecules against numerous diseases. The present review is endeavoring to highlight the progress in the various pharmacological activities of benzo[b]thiophene derivatives. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic benzothiophene-based medicinal drugs, as well as more effective diagnostic agents and pathologic probes. Also, SAR studies that highlight the chemical groups responsible for evoking the potential activities of benzothiophene derivatives are studied and compared.

N-heterocyclic carbene metal complexes as bio-organometallic antimicrobial and anticancer drugs.

Late transition metal complexes that bear N-heterocyclic carbene (NHC) ligands have seen a speedy growth in their use as both, metal-based drug candidates and potentially active homogeneous catalysts in a plethora of C-C and C-N bond forming reactions. This review article focuses on the recent developments and advances in preparation and characterization of NHC-metal complexes (metal: silver, gold, copper, palladium, nickel and ruthenium) and their biomedical applications. Their design, syntheses and characterization have been reviewed and correlated to their antimicrobial and anticancer efficacies. All these initial discoveries help validate the great potential of NHC-metal derivatives as a class of effective antimicrobial and anticancer agents.

Triazole: A Promising Antitubercular Agent.

Tuberculosis is a contagious disease with comparatively high mortality worldwide. The statistics shows that around three million people throughout the world die annually from tuberculosis and there are around eight million new cases each year, of which developing countries showed major share. Therefore, the discovery and development of effective antituberculosis drugs with novel mechanism of action have become an insistent task for infectious diseases research programs. The literature reveals that, heterocyclic moieties have drawn attention of the chemists, pharmacologists, microbiologists, and other researchers owing to its indomitable biological potential as anti-infective agents. Among heterocyclic compounds, triazole (1,2,3-triazole/1,2,4-triazole) nucleus is one of the most important and well-known heterocycles, which is a common and integral feature of a variety of natural products and medicinal agents. Triazole core is considered as a privileged structure in medicinal chemistry and is widely used as 'parental' compounds to synthesize molecules with medical benefits, especially with infection-related activities. In the present review, we have collated published reports on this versatile core to provide an insight so that its complete therapeutic potential can be utilized for the treatment of tuberculosis. This review also explores triazole as a potential targeted core moiety against tuberculosis and various research ongoing worldwide. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic triazole-based antituberculosis drugs.

A comprehensive review in current developments of benzothiazole-based molecules in medicinal chemistry.

Benzothiazole (BTA) and its derivatives are the most important heterocyclic compounds, which are common and integral feature of a variety of natural products and pharmaceutical agents. BTA shows a variety of pharmacological properties, and its analogs offer a high degree of structural diversity that has proven useful for the search of new therapeutic agents. The broad spectrum of pharmacological activity in individual BTA derivative indicates that, this series of compounds is of an undoubted interest. The related research and developments in BTA-based medicinal chemistry have become a rapidly developing and increasingly active topic. Particularly, numerous BTA-based compounds as clinical drugs have been extensively used in practice to treat various types of diseases with high therapeutic potency. This work systematically gives a comprehensive review in current developments of BTA-based compounds in the whole range of medicinal chemistry as anticancer, antibacterial, antifungal, antiinflammatory, analgesic, anti-HIV, antioxidant, anticonvulsant, antitubercular, antidiabetic, antileishmanial, antihistaminic, antimalarial and other medicinal agents. It is believed that, this review article is helpful for new thoughts in the quest for rational designs of more active and less toxic BTA-based drugs, as well as more effective diagnostic agents and pathologic probes.

Silver(I) complexes of mono- and bidentate N-heterocyclic carbene ligands: synthesis, crystal structures, and in vitro antibacterial and anticancer studies.

A series of benzimidazole-based N-heterocyclic carbene (NHC) proligands {1-benzyl-3-(2-methylbenzyl)-benzimidazolium bromide/hexafluorophosphate (1/4), 1,3-bis(2-methylbenzyl)-benzimidazolium bromide/hexafluorophosphate (2/5) and 1,3-bis(3-(2-methylbenzyl)-benzimidazolium-1-ylmethylbenzene dibromide/dihexafluorophosphate (3/6)} has been synthesized by the successive N-alkylation method. Ag complexes {1-benzyl-3-(2-methylbenzyl)-benzimidazol-2-ylidenesilver(I) hexafluorophosphate (7), 1,3-bis(2-methylbenzyl)-benzimidazol-2-ylidenesilver(I) hexafluorophosphate (8) and 1,3-bis(3-(2-methylbenzyl)-benzimidazol-2-ylidene)-1-ylmethylbenzene disilver(I) dihexafluorophosphate (9)} of NHC ligands have been synthesized by the treatment of benzimidazolium salts with Ag2O at mild reaction conditions. Both, NHC proligands and Ag-NHC complexes have been characterized by (1)H and (13)C{(1)H} NMR and FTIR spectroscopy and elemental analysis technique. Additionally, the structure of the NHC proligand 5 and the mononuclear Ag complexes 7 and 8 has been elucidated by the single crystal X-ray diffraction analysis. Both the complexes exhibit the same general structural motif with linear coordination geometry around the Ag centre having two NHC ligands. Preliminary in vitro antibacterial potentials of reported compounds against a Gram negative (Escherichia coli) and a Gram positive (Bacillus subtilis) bacteria evidenced the higher activity of mononuclear silver(I) complexes. The anticancer studies against the human derived colorectal cancer (HCT 116) and colorectal adenocarcinoma (HT29) cell lines using the MTT assay method, revealed the higher activity of Ag-NHC complexes. The benzimidazolium salts 4-6 and Ag-NHC complexes 7-9 displayed the following IC50 values against the HCT 116 and HT29 cell lines, respectively, 31.8 ± 1.9, 15.2 ± 1.5, 4.8 ± 0.6, 10.5 ± 1.0, 18.7 ± 1.6, 1.20 ± 0.3 and 245.0 ± 4.6, 8.7 ± 0.8, 146.1 ± 3.1, 7.6 ± 0.7, 5.5 ± 0.8, 103.0 ± 2.3 µM.

Comprehensive Review in Current Developments of Benzimidazole-Based Medicinal Chemistry.

The properties of benzimidazole and its derivatives have been studied over more than one hundred years. Benzimidazole derivatives are useful intermediates/subunits for the development of molecules of pharmaceutical or biological interest. Substituted benzimidazole derivatives have found applications in diverse therapeutic areas such as antiulcer, anticancer agents, and anthelmintic species to name just a few. This work systematically gives a comprehensive review in current developments of benzimidazole-based compounds in the whole range of medicinal chemistry as anticancer, antibacterial, antifungal, anti-inflammatory, analgesic agents, anti-HIV, antioxidant, anticonvulsant, antitubercular, antidiabetic, antileishmanial, antihistaminic, antimalarial agents, and other medicinal agents. This review will further be helpful for the researcher on the basis of substitution pattern around the nucleus with an aim to help medicinal chemists for developing an SAR on benzimidazole drugs/compounds.

Synthesis, crystal structures and characterization of late first row transition metal complexes derived from benzothiazole core: anti-tuberculosis activity and special emphasis on DNA binding and cleavage property.

Air and moisture stable coordination compounds of late first row transition metals, viz. Co(II), Ni(II), Cu(II) and Zn(II), with a newly designed ligand, 2-(2-benzo[d]thiazol-2-yl)hydrazono)propan-1-ol (LH), were prepared and successfully characterized using various spectro-analytical techniques. The molecular structures of the ligand and nickel complex were unambiguously determined by single-crystal X-ray diffraction method. The [Ni(LH)2]Cl2.3H2O complex is stabilized by intermolecular CH⋯π stacking interactions between the methyl hydrogen and the C18 atom of the phenyl ring (C11-H11B⋯C18) forming 1D zig-zag chain structure. Both, the ligand and its copper complex, were electrochemically active in the working potential range, showing quasi-reversible redox system. The interactions of all the compounds with calf thymus DNA have been comprehensively investigated using electronic absorption spectroscopy, viscosity, electrochemistry and thermal denaturation studies. The cleavage reaction on pBR322 DNA has been monitored by agarose gel electrophoresis. The results showed that the ligand can bind to CT-DNA through partial intercalation, whereas the complexes bind electrostatically. Further, [Ni(LH)2]Cl2.3H2O and [CuLCl(H2O)2] complexes in the series have high binding and cleavage affinity towards pBR322 DNA. Additionally, all the compounds were screened for anti-tuberculosis activity. All the complexes revealed an MIC value of 0.8 µg/mL, which is almost 8 times active than standard used (Streptomycin, 6.25 µg/mL).

Chromones as a privileged scaffold in drug discovery: a review.

The chromone and its derivatives are the most important heterocyclic compounds, which is a common and integral feature of a variety of natural products and medicinal agents. These heterocycles show a variety of pharmacological properties, and change of their structure offers a high degree of diversity that has proven useful for the search of new therapeutic agents. A large volume of research has been carried out on chromone and their derivatives, which has proved the pharmacological importance of this heterocyclic nucleus. The present review focuses on the pharmacological profile of chromone derivatives in the current literature with an update of recent research findings on this nucleus and the perspectives that they hold for future research.

Sterically tuned Ag(I)- and Pd(II)-N-heterocyclic carbene complexes of imidazol-2-ylidenes: synthesis, crystal structures, and in vitro antibacterial and anticancer studies.

Unsymmetrically substituted sterically tuned Pd(II)­NHC complexes of the general formula [PdCl2(NHC)2] (NHC = 1-allyl-3-methylimidazolin-2-ylidene, 7; 1-allyl-3-butylimidazol-2-ylidene, 8; 1-benzyl-3-butyl imidazolin-2-ylidene, 9) were prepared through transmetallation from their corresponding Ag(I)­NHC complexes. The Pd complexes were structurally characterized by different spectroscopic and X-ray diffraction methods. Complexes 7 and 9 adopted a trans­anti arrangement of the NHC ligands, whereas complex 8 adopted a cis­syn arrangement. Preliminary antibiogram studies using Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria showed that Ag(I)­NHC complexes demonstrate higher activity compared with Pd(I)­NHC complexes. Furthermore, Pd(II)­NHC complexes were evaluated for their anticancer potential using the human colorectal cancer cell line. A higher anticancer activity was observed for complexes 8 and 9, with 26.5 and 6.6 mM IC50 values, respectively.

3,3'-[1,2-Phenyl-enebis(methyl-ene)]bis-(1-ethyl-benzimidazolium) dibromide.

In the title mol-ecular salt, C(26)H(28)N(4) (2+)·2Br(-), the central benzene ring makes dihedral angles of 76.75 (11) and 82.40 (10)° with the pendant benzimidazole rings. The corresponding angle between the benzimidazole rings is 57.03 (9)°. In the crystal, the cations and anions are linked via C-H⋯Br hydrogen bonds, forming sheets lying parallel to the bc plane. The crystal structure also features weak C-H⋯π inter-actions.

Anticonvulsant activity and toxicity evaluation of Cu(II) and Zn(II) metal complexes derived from triazole-quinoline ligands.

A novel Cu(II) and Zn(II) complexes of triazolo-quinoline derivatives were synthesized by in situ method and were characterized by the spectro-analytical methods and their pharmacological properties were evaluated. The compound C3 has exhibited promising anticonvulsant activity towards the electroshock induced seizures in Wistar rats and possesses low toxicity, providing a high safety profile.

Metal-pyrazolyl diazine interaction: synthesis, structure and electrochemistry of binuclear transition metal(II) complexes derived from an 'end-off' compartmental Schiff base ligand.

Pyrazolyl diazine (mu-NN) bridged late first row transition metal(II) complexes have been prepared by the interaction of metal(II) chlorides with an 'end-off' compartmental Schiff base ligand. The ligand system has a strong diazine bridging component and obtained as a condensation product between 1H-pyrazole-3,5-dicarbohydrazide and 3-acetylcoumarin in absolute ethanol. All synthesized compounds are characterized on the basis of various spectral and analytical techniques. Complexes are found to be non-electrolytes and monomeric in nature. The magnetic exchange interactions are very weak because of the more electronegative exogenous chloride, though diazine bridging group bring metal centers in a close proximity.