Current Organocatalysis - Current Issue

The study aimed to employ one-pot solvent-free boric acid-catalyzed multicomponent reactions (MCRs) to synthesize bioactive thioamidoalkyl fluorescein analogs. The study aimed to introduce a facile and environmentally sustainable strategy for efficiently producing alternate potent bioactivity agents.

Population growth trends, limited efficacy and side effects of available medicine, and new challenges like antibiotic resistance have led to the urgent need for more and better pharmaceuticals and a notable increase in drug development. The global health demands and significant medicinal value of thioamidoalkyl compounds prompted synthesizing new fluorescein-based thioamidoalkyl derivatives to explore their prospective biomedical potential.

To prepare thioamidoalkyl fluorescein analogs, a solvent-free three-component reaction of fluorescein with aryl aldehydes and thiobenzamide catalyzed by boric acid was used. The antibacterial potentials of thioamidoalkyl fluorescein analogs against Escherichia coli (E. coli) bacteria were analyzed in terms of half-maximal inhibitory concentration (IC50). Moreover, molecular docking experiments explored the binding affinities and possible interaction mechanisms between newly synthesized analogs and active sites of E. coli adhesion protein FimH.

FTIR, ¹H, and ¹³C NMR results verified the successful formation of all analogs. The experimental and theoretical antibacterial activity results confirmed that the compound M-11 is relatively more potent against E. coli based on lower IC50 values of 54.14 nM and binding energy value of ‒6.30 kcal/mol (comparable to ‒6.70 kcal/mol of reference ligand) probably because of unique structure and strong binding affinities for target protein structure.

The findings demonstrated the potential of the currently employed synthetic approach to produce new analogs with decent yields facilely. Interestingly, the M-11 compound proved to be an excellent prospective source of antibiotic drugs based on both experimental and computational analyses.

Heterocyclic compounds emerged promising choice in drug discovery and clinical research. Among various heterocycles, 5-aryl-1,2,4-triazolidine-3-thione and 1,2,4-triazospiro-3-thione derivatives also showed important biological applications. Hence, organic chemists are striving to develop various catalytic routes for the construction of these derivatives.

The present work describes the eco-friendly synthesis of 5-aryl-1,2,4-triazolidine-3-thione (3a-o) and 1,2,4-triazospiro-3-thione (5p-u) via one-pot Multi-Component Reactions (MCRs) of substituted aromatic/heteroaromatic aldehyde, isatine and thiosemicarbazide in the presence of organocatalysts Glutamic acid (Glu) under microwave irradiation. Additionally, the homogeneity of the selected compounds was confirmed through various spectroscopic techniques such as FT-IR, 1H- 13C-NMR, and LC-MS. Further, the drug-likeness was evaluated using SwissADME software and the anti-microbial activity of the selected derivatives were tested.

The reaction exhibits good tolerance towards various substituted aromatic/heteroaromatic aldehydes, isatine, and thiosemicarbazide, resulting in high yields of product isolation (86–92%). The computational ADME properties of the prepared derivatives were evaluated for their drug-like properties, along with an assessment of Lipinski’s Rule of Five. Selected derivatives were also tested for their antimicrobial properties, showing comparable activities.

Overall, this work describes a greener method synthesis of 5-aryl-1,2,4-triazolidine-3-thione derivatives (3a-o) and 1,2,4-triazospiro-3-thione derivatives (5p-u). The catalysts used are biodegradable, environmentally friendly organocatalysts that align with green chemistry principles. The reaction is accelerated by microwave irradiation in the presence of ethanol. The developed method is simple, allowing for easy separation of the catalyst using hot ethanol and enabling recycling up to three times without affecting product isolation. The developed protocol offers advantages such as accessibility, cost-effectiveness, rapid reactions, mild atom economy, and elimination of hazardous solvents and catalysts usage. Selected derivatives were screened for antimicrobial activity, evaluated computationally for drug-likeness in silico, and adhered to Lipinski’s rule of five.

Peroxidases are heme-containing oxidoreductase enzymes that have the potential to oxidise a wide range of organic and inorganic substances in the presence of hydrogen peroxide. Peroxidase has the capability to bioremediate various toxic and carcinogenic phenolic and nonphenolic compounds, various pollutants, and polychlorinated hydrocarbons. Different types of organic and inorganic chemicals change the rate of enzyme-catalysed reactions binding with enzyme or enzyme-substrate complex. Enzyme activators increase enzyme activity, while enzyme inhibitors decrease it. Enzyme inhibition involves either complete or partial prevention of the enzymes' rate of reaction. We can use enzyme inhibitors to treat a variety of pathological disorders. Nowadays, enzyme inhibitors have become extremely beneficial compounds in our daily lives. They are commonly employed to cure diseases. Heavy metals, persistent inorganic chemical constituents, act as a form of poison to the enzyme’s reactivity. High amounts of heavy metals, such as Mn²⁺, Zn²⁺, and Fe²⁺, are poisonous even though they are crucial for plant physiology. Peroxidase production and activation are triggered by an excess of heavy metals as a defence system to scavenge the hydrogen peroxide molecules produced by metal toxicity. The binding of some heavy metals with peroxidase alters the active site’s conformations and reduces the enzyme activity even at low concentrations. Due to the presence of metal ions changing the enzyme’s reactivity and the broad application of peroxidases, it is necessary to study peroxidase activity in the presence of heavy metals.

The aim of this work was to study the enzyme activity in the presence of different heavy metal ions, such as Sr²⁺, Pb²⁺, Bi²⁺, Hg²⁺, Sn²⁺, Cd²⁺, Zn²⁺, Ni²⁺ Mo⁶⁺, etc. It also studied the nature of inhibition of peroxidase activity from radish sources in the presence of these metal ions.

The effect of heavy metal ions on the activity of peroxidase was studied by means of a direct spectrophotometric assay that monitors at 470 nm with the decrease of tetraguaiacol formation from guaiacol in the presence of H2O2 and metal ions with time. The nature of inhibition was studied by comparing the control experiment and the experiment with the addition of two different metal ion concentrations for the formation of tetraguaiacol at 470 nm from guaiacol in the presence of hydrogen peroxidase.

From this study, we have found that the metal ions like Mo⁶⁺, La²⁺, and Sr²⁺ inhibited the peroxidase enzyme very strongly, whereas the ions like Bi²⁺ and Cd²⁺ inhibited a bit weakly. The order of the inhibitory effect on radish peroxidase activity in the presence of different heavy metal ions was Pb²⁺ > Sr²⁺ > Hg²⁺ > Cd²⁺ > Bi²⁺=Sn²⁺ > Mo⁶⁺ > Zn²⁺ > Ni²⁺. The nature of inhibition on radish peroxidase activity of the Zn²⁺, Ni²⁺, and Sr²⁺ ions was found to be competitive; Cd²⁺, Pb²⁺, Hg²⁺, and Bi²⁺ ions were uncompetitive; and Sn²⁺ and Mo⁶⁺ ions were non-competitive.

In this study, the response of the peroxidase to various heavy metal ions like divalent Cd²⁺, Bi²⁺, Hg²⁺, Sn²⁺, Pb²⁺, Cd²⁺, Zn²⁺, and Ni²⁺ and hexavalent Mo⁶⁺ was studied, and it was found that these heavy metal ions significantly inhibited the radish peroxidase activity. With a rise in the concentration of Sr²⁺, Pb²⁺, Bi²⁺, Hg²⁺, Sn²⁺, Cd²⁺, Zn²⁺, Ni²⁺ and Mo⁶⁺ ions, the radish peroxidase slowly lost its activity. These inhibitors bound to the radish peroxidase active sites and prevented the substrates from binding, and thus, they lost their tendency for binding substrates.

Aromatization of dithioacetal derivatives is essential for the synthesis of bioactive compounds and drug design, playing a key role in pharmaceuticals, agrochemicals, and materials science. This study explores the synthesis and catalytic application of Cu2O nano hollow arrays in ring-expansion aromatization reactions of cyclic dithioacetal derivatives obtained from cyclohexanones.

By using Cu2O nano hollow arrays prepared through molecular templates and a simple hydrothermal process, the electrophilicity of N-bromosaccharin was enhanced, allowing for efficient and selective production of aromatic compounds with yields ranging from 63-96%. Copper acetate is transformed into Cu2O nano hollow arrays in aqueous media, with polyvinylpyrrolidone acting as a capping agent and (+)-L-tartaric acid as a structure-directing surfactant and multidentate ligand.

The synthesized Cu2O nano hollow arrays were characterized using transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) to verify their morphology, structure, and composition.

This method not only offers a cost-effective and environmentally friendly approach to synthesizing Cu2O with unique nano hollow structures, but also demonstrates their efficacy as catalysts in organic synthesis, particularly in the rarely reported ring-expansion aromatization of cyclic dithioacetal derivatives of cyclohexanone, emphasizing their broader applicability in materials science and catalysis.

The oxidation of aromatic primary alcohols is pivotal in organic synthesis, converting accessible starting materials into valuable intermediates. Traditional methods often rely on chromium-based reagents, which are hazardous and environmentally problematic. Ionic liquids, particularly those based on imidazolium cations, offer an attractive alternative due to their unique solvent properties and chemical stability. However, their application in oxidation reactions has been limited by challenges such as selectivity and efficiency. Recent advancements have focused on integrating chromium complexes into imidazolium ionic liquids to harness their catalytic potential. Understanding the catalytic efficiency and mechanistic insights of chromium-functionalized imidazolium di-cationic ionic liquids in alcohol oxidation is crucial for developing sustainable and efficient synthetic methodologies aiming to mitigate environmental impact and improve synthetic efficiency in organic chemistry.

The aim of this study was to synthesize, characterize, and explore the catalytic efficiency and mechanism of chromium-functionalized imidazolium di-cationic ionic liquids in the oxidation of aromatic primary alcohols.

The oxidation of benzyl alcohol was optimized by varying solvent and temperature parameters. Initially, benzyl alcohol was subjected to oxidation in different solvents: water, DMF, ACN, chloroform, 1,2-dichloroethane, and DMSO at room temperature. Solvent effects were evaluated, with DMF, ACN, and DMSO yielding approximately 80% conversion to the desired aldehyde. Interestingly, DCE did not yield the desired aldehyde. CHCl3 emerged as the optimal solvent, achieving a high yield of 94% in minimal reaction time. Temperature optimization revealed that at room temperature, the reaction required 40 minutes to reach 94% yield. Increasing the temperature to 60°C reduced the reaction time to 10 minutes while maintaining a high yield of 98%. Thus, 60°C was identified as the optimal temperature for maximizing both yield and reaction speed. The methodological adjustments of solvent and temperature parameters provided crucial insights for optimizing the oxidation of benzyl alcohol using chromium-functionalized imidazolium di-cationic ionic liquid.

Reactions at room temperature required longer times and yielded lower product amounts compared to reactions conducted at higher temperatures. Importantly, no over-oxidation to carboxylic acids was observed. Electron-donating groups on aromatic alcohol substrates led to higher yields of aldehydes in shorter times. Conversely, substrates with electron-withdrawing groups showed reduced yields (84% to 92%) over extended periods. Primary aliphatic alcohols exhibited lower yields even with prolonged reaction times, while secondary alcohols yielded fewer oxidation products. Recycling [DIL]²⁺[Cr2O7]^2- for four cycles showed decreased yields over successive uses, highlighting its potential for continuous catalytic use in alcohol oxidation.

In this study, imidazolium-based Di-cationic ionic liquid [DIL]²⁺[Cr2O7]^2- was synthesized, and its ionic liquid properties were demonstrated using TGA and DSC. Our developed catalyst efficiently converts primary aromatic alcohols to aldehydes using [DIL]²⁺[Cr2O7]^2- or [DIL]²⁺[Cr2O7]^2-/H5IO6, offering solvent-free rapid oxidation, catalyst recyclability for up to four cycles, and facile catalyst recovery. In comparison to other available oxidants, the developed protocol has a superior yield, ease of workup, ease of handling, and low hygroscopicity.

This paper presents the synthesis, spectroscopic characterization, and computational modeling of 4-Bromoquinoline-2-carboxaldehyde (4-BQCA), an effective therapeutic compound. 4-BQCA, a quinoline derivative, has drawn interest because of its distinct chemical structure and its medical uses.

The chemical was produced with excellent yield and purity using a simple, repeatable reaction route. Density functional theory (DFT) studies were carried out to learn more about the compound's molecular characteristics, including its electronic structure, bonding, and stability. The structure and functional groups found in 4-BQCA were verified by spectroscopic investigation, which included UV-Vis, FT-IR, NMR, and mass spectrometry.

The compound's stability and advantageous electrical characteristics are highlighted by the results of both computational and experimental methods, indicating that it may find application in medication design and development.

These results offer a starting point for further investigations into the biological activity and therapeutic effectiveness of 4-BQCA, indicating that it is a viable option for more study in pharmaceutical applications.

The study explores the biosynthesis of silver nanoparticles (AgNPs) using extracellular manganese peroxidase enzyme from Trichoderma parestonica. The synthesis was optimized at a 1:1 enzyme and silver nitrate ratio, pH 12, shaking process, and 48-hour synthesis period. The AgNPs were characterized using spectroscopic and microscopic techniques, showing absorbance in UV-spectroscopy between 410-450 nm due to Surface Plasmon Resonance (SPR).

The stabilization of extracellular manganese peroxidase with the nanoparticles through capping was observed by Fourier Transform Infrared Spectroscopy (FT-IR). The spherical shape of the AgNPs, with an average size of 69.09 nm, is confirmed by the Field Emission Scanning Electron Microscopy (FESEM) study. The size of the nanoparticles was also determined by Dynamic Light Scattering (DLS) to be 75.99 nm. When synthesized AgNPs were used to decolorize Alizarin red S (ARS), Methylene Blue (MB), and Methyl Orange (MO) in the presence of sodium borohydride reducing agent, the results showed that, within 20 minutes, 90% of 0.1 mM ARS, MB, and 75% 0.1 mM MO were degraded.

This study demonstrated the potential of AgNPs synthesized from MnP enzyme in nano-remediation projects, offering a sustainable solution to the problems and issues of dye-induced wastewater pollution and fostering environmental conservation.

Enzymes are being studied in nanotechnology, leading to the development of enzyme nanoparticles, which can be utilized in various fields like biosensors agriculture, drug delivery, and bioremediation.