Recent Progress in the Multicomponent Synthesis of Pyran Derivatives by Sustainable Catalysts under Green Conditions.

Pyrans are one of the most significant skeletons of oxygen-containing heterocyclic molecules, which exhibit a broad spectrum of medicinal applications and are constituents of diverse natural product analogues. Various biological applications of these pyran analogues contributed to the growth advances in these oxygen-containing molecules. Green one-pot methodologies for synthesising these heterocyclic molecules have received significant attention. This review focuses on the recent developments in synthesising pyran ring derivatives using reusable catalysts and emphasises the multicomponent reaction strategies using green protocols. The advantages of the catalysts in terms of yields, reaction conditions, and recyclability are discussed.

The pioneering role of metal-organic framework-5 in ever-growing contemporary applications - a review.

MOF-5 with a Zn(ii) cluster and terephthalic acid is a distinctive porous material among the metal-organic frameworks (MOFs), with unique physical, chemical and mechanical properties. MOF-5 based composites possess ample applications in modern chemistry. Huge surface area, suitable pore dimensions and scope of tunability make MOF-5 noteworthy in advanced materials. The extensive features of MOF-5 provided an opportunity for researchers to explore atomic/molecular scale materials. Various MOF-5 based composites have been designed with revamped properties appropriate to the application by altering and fabricating MOF-5 in situ or using a post-synthetic approach. Surface modification via the dispersion and impregnation of active substances into the pores of MOF-5 enhances its applicability. The boundless topologies and morphologies of MOF-5 combined with other chemical entities has provided opportunities in various fields, including catalysis, gas storage and sensors. The present review illuminates the leading role of MOF-5 and its composites in contemporary applications based on the current literature in heterogeneous catalysis, H2 and CO2 storage and sensors.

Advances in Pyranopyrazole Scaffolds' Syntheses Using Sustainable Catalysts-A Review.

Heterogeneous catalysis plays a crucial role in many chemical processes, including advanced organic preparations and the design and synthesis of new organic moieties. Efficient and sustainable catalysts are vital to ecological and fiscal viability. This is why green multicomponent reaction (MCR) approaches have gained prominence. Owing to a broad range of pharmacological applications, pyranopyrazole syntheses (through the one-pot strategy, employing sustainable heterogeneous catalysts) have received immense attention. This review aimed to emphasise recent developments in synthesising nitrogen-based fused heterocyclic ring frameworks, exploring diverse recyclable catalysts. The article focused on the synthetic protocols used between 2010 and 2020 using different single, bi- and tri-metallic materials and nanocomposites as reusable catalysts. This review designated the catalysts' efficacy and activity in product yields, reaction time, and reusability. The MCR green methodologies (in conjunction with recyclable catalyst materials) proved eco-friendly and ideal, with a broad scope that could feasibly lead to advancements in organic synthesis.

A Facile and Catalyst-Free Microwave-Promoted Multicomponent Reaction for the Synthesis of Functionalised 1,4-Dihydropyridines With Superb Selectivity and Yields.

We report a highly efficient green protocol for developing a novel library of 1,2,4-triazole-tagged 1,4-dihydropyridine analogs through the one-pot process from the four-component fusion of the 1H-1,2,4-triazol-3-amine with different chosen aldehydes, diethyl acetylenedicarboxylate, and active methylene compounds in a water medium under microwave irradiation and catalyst-free conditions. Excellent yields (94-97%) of the target products were achieved with high selectivity with a short reaction time (<12 min) at room temperature. The structures of the synthesized pyrimidine analogs were established by NMR and HRMS spectroscopic analysis. Simple workup, impressive yields, no column chromatography, green solvent, rapid reaction, and excellent functional group tolerance are the benefits of this protocol.

Recent Progresses in the Multicomponent Synthesis of Dihydropyridines by Applying Sustainable Catalysts Under Green Conditions.

The synthesis of dihydropyridines, valuable molecules with diverse therapeutic properties, using eco-friendly heterogeneous catalysts as a green alternative received significant consideration. By selecting appropriate precursors, these compounds can be readily modified to induce the desired properties in the target product. This review focused on synthesising diverse dihydropyridine derivatives in single-pot reactions using magnetic, silica, and zirconium-based heterogeneous catalytic systems. The monograph describes preparation techniques for various catalyst materials in detail. It covers facile and benign magnetic, silica, zirconium-based, and ionic liquid catalysts, exhibiting significant efficacy and consistently facilitating excellent yields in short reaction times and in a cost-effective way. Most of the designated protocols employ Hantzsch reactions involving substituted aldehydes, active methylene compounds, and ammonium acetate. These reactions presumably follow Knoevenagel condensation followed by Michael addition and intra-molecular cyclisation. The multicomponent one-pot protocols using green catalysts and solvents have admirably increased the product selectivity and yields while minimising the reaction time. These sustainable catalyst materials retain their viability for several cycles reducing the expenditure are eco-friendly.

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications.

The analogs of nitrogen-based heterocycles occupy an exclusive position as a valuable source of therapeutic agents in medicinal chemistry. More than 75% of drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties. In the forthcoming decade, a much greater share of new nitrogen-based pharmaceuticals is anticipated. Many new nitrogen-based heterocycles have been designed. The number of novel N-heterocyclic moieties with significant physiological properties and promising applications in medicinal chemistry is ever-growing. In this review, we consolidate the recent advances on novel nitrogen-containing heterocycles and their distinct biological activities, reported over the past one year (2019 to early 2020). This review highlights the trends in the use of nitrogen-based moieties in drug design and the development of different potent and competent candidates against various diseases.

In silico molecular docking and in vitro antioxidant activity studies of novel α-aminophosphonates bearing 6-amino-1,3-dimethyl uracil.

In the present study, a new series of α-Aminophosphonates bearing 6-amino-1,3-dimethyluracil was synthesized in good to excellent yields (78-95%) by one-pot, three-component reaction of 6-amino-1,3-dimethyluracil, aromatic aldehydes and diethylphosphite via Kabachnik-Fields reaction by using an eco-friendly Eaton's reagent. All the compounds were screened for in vitro antioxidant studies by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) methods. Among the synthesized bioactive molecules, 4a, 4d, 4g, and 4h exhibited promising antioxidant activity compared with the standard drug Ascorbic acid. Furthermore, in order to support the biological results of the compounds, molecular docking studies were performed against Aromatase enzyme for four compounds which revealed that the compounds 4a, 4d, 4g, and 4h have significant binding modes, with docking scores of -8.6, -8.4, -8.1 and -8.1 respectively and the compound 4b specifically has equal dock score of -8.0 when compared with the standard drug Exemestane.

Green synthesis and characterisation of novel [1,3,4]thiadiazolo/benzo[4,5]thiazolo[3,2-a]pyrimidines via multicomponent reaction using vanadium oxide loaded on fluorapatite as a robust and sustainable catalyst.

We synthesised materials with different loadings of vanadia on fluorapatite (V2O5/FAp), fully characterised their structural properties using various spectral techniques including TEM, BET, XRD, FT-IR, SEM and EDX and assessed their prowess as catalysts. The 2.5% V2O5/FAp exhibited excellent activity for the synthesis of novel [1,3,4]thiadiazolo[3,2-a]pyrimidines and benzo[4,5]thiazolo[3,2-a]pyrimidines. The one-pot three-component fusion reaction between chosen substrates of 1,3,4-thiadiazole-amines or 2-amino-benzothiazole, aldehydes and active methylene compounds in ethanol solvent at room temperature gave an excellent yield of products (90-97%) in a swift reaction (25-30 min). The advantages of this protocol are rapid synthesis, mild reaction conditions, green solvent, easy work-up, eco-friendliness, reusability of catalyst and no need for column chromatography.

Drug screening of rhodanine derivatives for antibacterial activity.

Introduction: Bacteriological infections are a major risk to human health. These include all hospital and public-acquired infections. In drug discovery, rhodanines are privileged heterocyclic frameworks. Their derivatives possess strong anti-bacterial activity and some of them have shown potent activity against multidrug-resistant pathogens, both under in vitro and in vivo conditions. To treat multi-drug resistant pathogens, the development of novel potent drugs, with superior anti-bacterial efficacy, is paramount. One avenue which shows promise is the design and development of novel rhodanines.Areas covered: This review summarizes the status on rhodanine-based derivatives and their anti-bacterial activity, based on published research over the past six years. Furthermore, to facilitate the design of novel derivatives with improved functions, their structure-activity relationships are assessed with reference to their efficacy as anti-bacterial agents and their toxicity.Expert opinion: The pharmacological activity of molecules bearing a rhodanine scaffold needs to be very critically assessed in spite of considerable information available from various biological evaluations. Although, some data on structure-activity relationship frameworks is available, information is not adequate to optimize the efficacy of rhodanine derivatives for different applications.

Four-Component Fusion Protocol with NiO/ZrO2 as a Robust Recyclable Catalyst for Novel 1,4-Dihydropyridines.

Nickel oxide loaded on zirconia (NiO/ZrO2) as an expedient catalyst is reported for the synthesis of 18 unsymmetrical 1,4-dihydropyridine derivatives. The Lewis acidic nature of the catalyst proved an excellent choice for the one-pot, four-component fusion reaction with excellent yields of 89-98% and a completion time of 20-45 min. Mechanistic studies show that enamine and imine functionalities are the two possible pathways for the formation of 1,4-dihydropyridines with high selectivity. Crystal structures of two novel compounds (5a, 5c) were reported. The catalyst demonstrated reusability up to six cycles. The reaction at room temperature and ethanol as a solvent make this protocol green and economical.

A facile and one-pot synthesis of new tetrahydrobenzo[b]pyrans in water under microwave irradiation.

Eleven new tetrahydrobenzo[b]pyran derivatives were synthesized via a three component reaction of different aromatic aldehydes, methyl cyanoacetate and 1,3-cyclohexadione, with water as solvent under catalyst-free microwave irradiation. The structures of all the new molecules were well analysed and their structures established by using various spectral techniques (1H NMR, 13C NMR, 15N NMR and HRMS). Various advantages of reported protocol are the ease of preparation, short reaction times (10 min), aqueous solvent and excellent yields (89-98%). Additionally, this method provides a clean access to the desired products by simple workup.

Ozone facilitated degradation of caffeine using Ce-TiO2 catalyst.

The ozone initiated oxidation of 1,3,7-trimethylxanthine (caffeine), commonly found in wastewaters as model compound is reported using cerium (Ce)/titanium dioxide (TiO2) as catalyst. The effect of pH and loading of ceria on titania were investigated. Effect of reaction conditions on degradation of caffeine based on their pseudo first-order rate constants were compared. The combination of catalyst Ce-TiO2 and ozone aeration significantly enhanced the degradation of caffeine compared to uncatalysed ozonation. The oxidation of caffeine ensued via the free radical mechanism, through enhanced ozone decomposition into OH radicals. Ce/TiO2(0.5 wt%) showed good activity in degradation of caffeine at pH 6, in both natural stream and river water samples showing about 60% total organic carbon removal in 2 h ozonation period. Using liquid chromatography-mass spectroscopy, degradation products were analysed. A reaction intermediate and one final product were positively identified. Nano-catalysts with different loadings of Ce on TiO2 synthesized by sol-gel route were characterized by scanning electron microscope, transmission electron microscopy, BET and powder X-ray diffraction spectrum techniques. The results showed that the material retained a highly ordered mesoporous structure and possessed large surface area.

A multicomponent, facile and catalyst-free microwave-assisted protocol for the synthesis of pyrazolo-[3,4-b]-quinolines under green conditions.

A facile, swift and ecofriendly microwave-assisted multi-component/one-pot protocol is designed for the synthesis of novel pyrazolo-[3,4-b]-quinolines at ambient temperature in aqueous ethanol as a reaction medium. The 18 novel pyrazolo-[3,4-b]-quinoline derivatives were synthesized by fusion of chosen aryl aldehyde, dimedone and 5-amino-3-methyl-1-phenylpyrazole in excellent yields (91-98%). All the molecular structures were confirmed by 1H-NMR, 15N-NMR, 13C-NMR, and HRMS data analysis. Operational simplicity, easy handling, one-step simple workup procedure, mild reaction conditions, short reaction time (≤10 min), high selectivity and no by-product formation are the striking features of the protocol.

A review on novel composites of MWCNTs mediated semiconducting materials as photocatalysts in water treatment.

Many technologies were explored to eliminate the harmful pollutants entering water systems and to minimize their impact on environment. In general, photo-catalysis is one of the sustainable techniques with wider applications and semiconductors in particular were efficiently utilized in the photocatalytic degradation of pollutants. Semiconducting materials, such as TiO2, ZnO, BiO, CdS, and Ag3PO4 are frequently used as photo-catalysts due to their suggestible band gap and structural properties. The generation of reactive oxygen species such as hydroxyl and superoxide radicals is the crucial factor in degradation of pollutant molecules. The rapid recombination of photo-generated electron-hole pairs impacts on the efficacy of semiconductors as photo-catalysts. The integration of properties of multi-walled carbon nanotubes (MWCNTs) with semiconductors is considered as imperative alternative strategy to boast the photocatalytic efficiency. The combinative merits of composites of MWCNTs and various semiconductor materials give new vista for water treatment and environmental protection. This review describes the scope of different types of MWCNT and semiconductor composites as photo-catalysts and their structure-property relationships in oxidative degradation and mineralization of organic pollutants, in particular.

Our Contributions in Synthesis of Diverse Heterocyclic Scaffolds by Using Mixed Oxides as Heterogeneous Catalysts.

This personal account mainly introduces and reviews our recent contributions in developing different catalyst materials involving mixed oxides and their scope as renewable catalysts in multicomponent reactions to synthesize various novel heterocyclic scaffolds under green conditions. The application of various mixed oxides and their composites in the organic synthesis is emphasized through this review, in order to reveal the versatility, scope and importance of mixed oxides and their interactions during the reaction. We have also briefed the limitations of mixed oxides as catalysts, to put forward the broader prospective in the field.

Ag2O on ZrO2 as a Recyclable Catalyst for Multicomponent Synthesis of Indenopyrimidine Derivatives.

We describe the synthesis of silver loaded on zirconia and its use as an efficient catalyst for a one-pot three-component reaction to synthesize 11 indenopyrimidine derivatives, of which 7 are new compounds. The procedure involves substituted benzaldehydes, indane-1,3-dione, and guanidinium hydrochloride, with ethanol as solvent. The proposed green protocol at room temperature is simple and efficient, giving excellent yields (90⁻96%) in short reaction times (<30 min). The protocol works well according to the green chemistry principles with respect to high atom economy, no need for column separation, and reusability of the catalyst, which are attractive features. XRD, TEM, SEM, and BET analysis were used to characterize the catalyst materials.

Ozone initiated inactivation of Escherichia coli and Staphylococcus aureus in water: Influence of selected organic solvents prevalent in wastewaters.

Absorption, stability and reactivity of ozone in water are critical parameters to determine its efficiency in microbial inactivation. In this study, the influence of four water-soluble organic solvents commonly discharged from industrial lines into wastewater systems, namely; ethanol, methanol, ethyl acetate and dimethyl sulfoxide (DMSO) on the ozone-facilitated inactivation of Escherichia coli and Staphylococcus aureus in water was investigated. Ozone absorption (up to 12 min) as a function of ozone aeration time, and the decomposition rate were spectrophotometrically monitored in the presence of 2.5% and 5% concentrations of each organic solvent. Their consequent effect on bacterial inactivation was determined. The inactivation kinetics were described using the efficiency factor Hom model. Residual concentrations of absorbed ozone in solutions with ethyl acetate or DMSO were relatively higher than those in methanol or ethanol-containing solutions. DMSO and ethyl acetate enhanced the stability of ozone in water, characterised by a lower decomposition rate constant in DMSO (kd = 3.81 × 10-2 M-1 s-1) and ethyl acetate (kd = 4.45 × 10-2 M-1 s-1) solutions, in contrast with that in methanol (kd = 1.13 × 10-1 M-1 s-1), where the decomposition rate was higher. The faster absorption and stability of ozone in ethyl acetate and DMSO corresponded with an observed increase in the log inactivation of E. coli and S. aureus by approximately 2-fold relative to that in methanol.

An efficient and green approach for the synthesis of 2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylates using Bi2O3/ZrO2 as a reusable catalyst.

A novel material of bismuth loaded on zirconia (Bi2O3/ZrO2) is synthesized by simple wet-impregnation method and characterized by several techniques (P-XRD, TEM, SEM, BET, etc.). Bi2O3/ZrO2 proved to be a good catalyst for the four-component, one-pot reaction to produce a new series of 2,4-dihydropyrano[2,3-c]pyrazole-3-carboxylate derivatives with excellent yields (91 to 98%) under mild conditions at RT with short reaction times (≈20 min). The structures of the target molecules were confirmed by 1H NMR, 13C NMR, 15N NMR, HRMS and FT-IR. The catalyst is easily separable and can be reused for six cycles without ostensible loss of activity. This method is inexpensive, atom-efficient and no chromatographic separations are needed.

Chlorine dioxide oxidation of Escherichia coli in water - A study of the disinfection kinetics and mechanism.

This study investigated the kinetics and mechanism of chlorine dioxide (ClO2) inactivation of a Gram-negative bacteria Escherichia coli (ATCC 35218) in oxidant demand free (ODF) water in detail as a function of disinfectant concentration (0.5-5.0 mg/L), water pH (6.5-8.5), temperature variations (4-37°C) and bacterial density (105-107 cfu/mL). The effects of ClO2 on bacterial cell morphology, outer membrane permeability, cytoplasmic membrane disruption and intracellular enzymatic activity were also studied to elucidate the mechanism of action on the cells. Increasing temperature and disinfectant concentration were proportional to the rate of cell killing, but efficacy was found to be significantly subdued at 0.5 mg/L and less dependent on the bacterial density. The bactericidal efficiency was higher at alkaline pH of 8 or above as compared to neutral and slightly acidic pH of 7 and 6.5 respectively. The disinfection kinetic curves followed a biphasic pattern of rapid inactivation within the initial 2 min which were followed by a tailing even in the presence of residual biocide. The curves were adequately described by the Cavg Hom model. Transmission Electron Microscopy images of the bacteria cells exposed to lethal concentrations of ClO2 indicated very little observable morphological damage to the outer membranes of the cells. ClO2 however was found to increase the permeability of the outer and cytoplasmic membranes leading to the leakage of membrane components such as 260 nm absorbing materials and inhibiting the activity of the intracellular enzyme ß-D-galactosidase. It is suggested that the disruption of the cytoplasmic membrane and subsequent efflux of intracellular components result in the inactivation of the Gram-negative bacteria.

Synthesis, Molecular Docking Study and in vitro Anticancer Activity of Tetrazole Linked Benzochromene Derivatives.

BACKGROUND: Globally, cancer is regarded as one of the biggest health concern in humans and animals and is one of the most terrifying diseases. Therefore, there is a necessity for the discovery, development and improvement of novel antitumor drug molecules which could efficiently prevent proliferative pathways and clonal expansion of cells. Heterocyclic compounds like benzochromene play a key role in the development of current pharmaceuticals, natural resources, agriculture products, analytical reagents and dyes. Therefore, anticancer drugs show increased resistance, it is essential to designing the novel structured heterocyclic moieties to create potential anticancer agents with promising biological applications. OBJECTIVE: To synthesis a novel 1-(substitutedphenyl)-2-(1H-tetrazol-5-yl)-1H-benzo[f]chromene-3-amine derivatives for in vitro antitumour activity. METHOD: The reaction of 3-amino-1-(substitutedphenyl)-1H-benzo[f]chromene-2-carbonitrile with sodium azide, ammonium chloride in dimethyl formamide solvent under reflux condition for 4 h afforded products (3a-k). The synthesized molecules were subjected to possible potential anti-tumour activity in vitro in four human cancer cell lines (MCF-7, Caco-2, HeLa and SKBR-3), and one human non-cancer cell line (HEK293), using the MTT cell viability assay. RESULTS: A novel series of products (3a-k) were synthesized with good yield and were identified with 1H NMR, 15N NMR, 13C NMR, FT-IR and HR-MS spectrum. The most potent compounds 3d, 3e, and 3f possessing the greatest cytotoxicity activity with IC50 values slightly higher (15-33 µM) than that of 5-Fluorouracil (10-17 µM), indicating their potential to be antitumor agents. The 3a, 3b, 3c, 3h, 3i and 3j compounds showed moderate activity. Additionally, a molecular docking analysis was conducted to predict the multi-drug resistance modulator behavior of synthesized compounds in the ATP binding site of P-glycoprotein. CONCLUSIONS: We synthesized and designated eleven novel derivatives of tetrazole linked benzochromenes (3a-k) and evaluated their anti-cancer activity. Additionally, the results from the docking studies were found to be in good agreement with the results from computational profiling.