Visible-Light-Mediated Synthesis of Thioesters Using Thiocarboxylic Acid as the Dual Reagent.

We have developed a visible-light-driven method for thioester synthesis that relies on the unique dual role of thiobenzoic acids as one-electron reducing agents and reactants leading to the formation of sulfur radical species. This synthetic process offers a wide scope, accommodating various thioacid and thiol substrates without the need for a photocatalyst.

Adsorptive avidity of Prussian blue polypyrrole nanocomposite for elimination of water contaminants: a case study of malachite green and isoniazid.

Persistent water contaminants include a variety of substances that evade natural cleaning processes posing severe risks to ecosystems. Their adsorptive elimination is a key approach to safer attenuation. Herein we present the design and development of Prussian blue incorporated polypyrrole (PPY/PB) hybrid nanocomposite as a high-performance adsorbent for the elimination of malachite green (M.G.), isoniazid (INH) and 4-nitrophenol (4-NP) water contaminants. The nanocomposite synthesis was favored by strong dopant-polymer interactions, leading to a PPY/PB material with enhanced electro-active surface area compared to pristine PPY. The structure-activity response of the nanocomposite for the adsorption of target contaminants was unveiled by evaluating its maximum adsorption capacities under environmentally viable conditions. In-depth analysis and optimization of adsorption influencing factors (pH, temperature, and adsorbent dose) were performed. Using equilibrium studies, kinetic model fitting, aided with FTIR analysis, a multi-step mechanism for the adsorption of target contaminants on the nanocomposite was proposed. Furthermore, the PPY/PB nanocomposite also acts as a catalyst, enabling contaminant elimination following a synergistic scheme that was demonstrated using 4-NP contaminant. The synergetic adsorption and catalytic degradation of 4-NP using PPY/PB as adsorbent and catalyst was demonstrated in the presence of NaBH4 as a reducing agent in absence of light. In summary, this work highlights the targeted design of adsorbent, its optimization for adsorptive avidity, and the synergistic role of adsorption trapping in the catalytic degradation of persistent contaminants.

Studies towards investigation of Naphthoquinone-based scaffold with crystal structure as lead for SARS-CoV-19 management.

In this work, 1-(4-bromophenyl)-2a,8a-dihydrocyclobuta[b]naphthalene-3,8­dione (1-(4-BP)DHCBN-3,8-D) has been characterized by single crystal X-ray to get it's crystal structure with R(all data) - R1 = 0.0569, wR2 = 0.0824, 13C and 1HNMR, as well as UV-Vis and IR spectroscopy. Quantum chemical calculations via DFT were used to predict the compound structural, electronic, and vibrational properties. The molecular geometry of 1-(4-BP)DHCBN-3,8-Dwas optimized utilizing the B3LYP functional at the 6-311++G(d,p) level of theory. The Infrared spectrum has been recorded in the range of 4000-550 cm-1. The Potential Energy Distribution (PED) assignments of the vibrational modes were used to determine the geometrical dimensions, energies, and wavenumbers, and to assign basic vibrations. The UV-Vis spectra of the titled compound were recorded in the range of 200-800 nm in ACN and DMSO solvents. Additionally, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy gap and electronic transitions were determined using TD-DFT calculations, which also simulate the UV-Vis absorption spectrum. Natural Bond Orbital (NBO) analysis can be used to investigate electronic interactions and transfer reactions between donor and acceptor molecules. Temperature-dependent thermodynamic properties were also calculated. To identify the interactions in the crystal structure, Hirshfeld Surface Analysis was also assessed. The Molecular Electrostatic Potential (MEP) and Fukui functions were used to determine the nucleophilic and electrophilic sites. Additionally, the biological activities of 1-(4-BP)DHCBN-3,8-D were done using molecular docking. These results demonstrate a significant therapeutic potential for 1-(4-BP)DHCBN-3,8-D in the management of Covid-19 disorders. Molecular Dynamics Simulation was used to look at the stability of biomolecules.

Visible-Light-Promoted Oxidative Annulation of Naphthols and Alkynes: Synthesis of Functionalized Naphthofurans.

A visible-light-mediated site-selective oxidative annulation of naphthols with alkynes for the synthesis of functionalized naphthofurans has been developed. The reaction relies on the in situ formation of an electron donor acceptor pair between phenylacetylene and thiophenol as the light-absorbing system to obviate the requirement of an added photocatalyst. The protocol facilitates the transformation of 1-naphthol and 2-naphthol as well as 1,4-naphthoquinone into a wide variety of highly functionalized naphthofurans.

Bioactive supra decorated thiazolidine-4-carboxylic acid derivatives attenuate cellular oxidative stress by enhancing catalase activity.

A pharmacophoric motif decorated with supramolecular functionalities (TZT) was designed for potential interaction with biological targets. Main insights of this work include the correlation of supra functionalities of TZT with its binding ability to proteins leading to the modulation of their structure and bioactivity as a promising perspective in the field of cellular protection from oxidative stress. To investigate the role of TZT in obliterating oxidative stress at a molecular level, its binding propensity with bovine serum albumin (BSA) and bovine liver catalase (BLC) was characterized using various biophysical methods. The binding constants of TZT with BSA (Kb = 2.09 × 105 M-1) and BLC (Kb = 2.349 × 105 M-1) indicate its considerable interaction with these proteins. TZT efficiently triggers favourable structural changes in BLC, thereby enhancing its enzyme activity in a dose dependent manner. The enzyme kinetics parameters of TZT binding to BLC were quantified using the Michaelis-Menten model. Both in silico and experimental results suggest that an increased substrate availability could be the reason for enhanced BLC activity. Furthermore, physiological relevance of this interaction was demonstrated by investigating the ability of TZT to attenuate oxidative stress. Treatment with TZT was found to mitigate the inhibition of A549 cell proliferation in the presence of high concentrations of vitamin C. This finding was confirmed at a molecular level by PARP cleavage status, demonstrating that TZT inhibits apoptotic cell death induced by oxidative stress.

Visible Light-Mediated [2 + 2] Cycloaddition Reactions of 1,4-Quinones and Terminal Alkynes.

A single-step synthesis of 4-hydroxy-functionalized bi-aryl and aryl/alkyl ketones via oxidative coupling of terminal alkynes with benzoquinones is reported. Furthermore, with naphthoquinones, owing to the cross-resonance of carbonyl with the aromatic ring, alkene-alkyne cycloaddition is more favored to give four-membered carbocyclic adducts, thereby precluding the requirement of preactivated alkynes.

Acyl Radicals from Terminal Alkynes: Photoredox-Catalyzed Acylation of Heteroarenes.

A photoredox-mediated acylation reaction of electron deficient heteroarenes with terminal alkynes is reported. The method relies on oxidative cleavage of phenylacetylenes for generation of acyl radicals as a key enabling feature. The reaction is regioselective with broad substrate scope. Quantum yield investigations support a radical chain mechanism.

Photoredox Generated Vinyl Radicals: Synthesis of Bisindoles and ß-Carbolines.

A photoredox catalyzed approach enabling use of alkynes as surrogate of 2-oxoaldehydes/1,2-diones is reported. The method overcomes the difficulty associated with application of unsubstituted aliphatic α-oxoaldehydes, which has hitherto limited their general use. Indoles, tryptamine, and tryptophan methyl ester participated in the reaction to give a variety of α-oxo based analogues. Quantum yield investigations support a radical chain mechanism.

An investigation of in vitro cytotoxicity and apoptotic potential of aromatic diselenides.

A target synthesis of a library of symmetric aromatic diselenides was attempted with the aim of generating anticancer lead compounds. Out of thirteen screened molecules (1-13) against a panel of human cancer cell lines, compound 8 exhibited highest cell growth inhibition in Human leukemia HL-60 cells with IC50 value of 8 µM. Compound 8 had a good pro-apoptotic potential as evidenced from several apoptotic protocols like DNA cell cycle analysis and monitoring of apoptotic bodies formation using phase contrast and nuclear microscopy with Hoechst 33,258. Also, 8 significantly inhibits S phase of the cell cycle and eventually trigger apoptosis in HL-60 cells through mitochondrial dependent pathway substantiated by the loss of mitochondrial potential. A theoretical investigation of DNA binding ability of 8 showed that it selectively bind to minor groove of DNA, where it is stabilized by hydrogen bonding and hydrophobic interactions.

Design and development of symmetric aromatic bischalcogenide-based photocatalysts for water treatment application: a concise study of diphenyl diselenide polypyrrole nanocatalysis.

Dopant engineering can be a very selective approach in designing hybrid materials. Incorporating the required functionality in a dopant effectively modulates its properties towards aimed applications. Consequently, this work through a comparative study envisaged the incorporation of chalcogenides (S, Se, and Te) in a biphenyl motif based on the analysis of major photocatalytic descriptors. Bischalcogenides as tuned dopants have been impressive in enhancing the surface area, increasing crystallinity and facilitating band gap shifts towards better light harvesting. In addition, the chalcogen effect was observed to induce preferential ion migration, leading to effective charge separation and attenuated recombination rates. Photocatalytic descriptors evaluated from electrochemical impedance spectroscopy and photoluminescence data corroborated the chalcogen effect in the observed trend (Ph)2 < (PhS)2 < (PhSe)2 < (PhTe)2. The diphenyl diselenide polypyrrole nanocomposite emerged to be better among the studied systems. (PhSe)2/PPY was characterized and comprehensively evaluated for its photocatalytic activity towards varied dye classes and the colorless isoniazid antibiotic under environmentally viable conditions. Its calculated band potential values and scavenger experiments indicate OH˙ and O2 ˙- as dominant species in its photocatalytic activity. Control experiments confirmed photocatalytic degradation over photolysis as the dye decolouration mechanism. Taken together, (PhSe)2/PPY emerges as a good propensity photocatalyst worthy of real time customization for wastewater treatment on a pilot scale.

Modular access to sulfur substituted analogues of isocytosine via photoredox catalysis.

A photoredox approach for synthesizing sulfur-substituted analogues of isocytosine via coupling of modular phenyl propargyl chloride with thiourea has been reported. The resulting product with an amine group was found amenable to various late-stage modifications, providing access to a broad range of sulfur-containing isocytosine derivatives.

Privileged Scaffolds in Drug Discovery against Human Epidermal Growth Factor Receptor 2 for Cancer Treatment.

HER2 is the membrane receptor tyrosine kinase showing overexpression in several human malignancies, particularly breast cancer. HER2 overexpression causes the activation of Ras- MAPK and PI3K/Akt/ NF-κB cellular signal transduction pathways that lead to cancer development and progression. HER2 is, therefore, presumed as one of the key targets for the development of tumor-specific therapies. Several preclinical have been developed that function by inhibiting the HER2 tyrosine kinase activity through the prevention of the dimerization process. Most HER2 inhibitors act as ATP competitors and prevent the process of phosphorylation, and abort the cell cycle progression and proliferation. In this review, the clinical drug candidates and potent pre-clinical newly developed molecules are described, and the core chemical scaffolds typically responsible for anti-HER2 activity are deciphered. In addition, the monoclonal antibodies that are either used in monotherapy or in combination therapy against HER2-positive cancer are briefly described. The identified key moieties in this study could result in the discovery of more effective HER2-targeted anticancer drug molecules and circumvent the development of resistance by HER2-specific chemotherapeutics in the future.

Visible-Light-Mediated Synthesis of N-Acyl-N,O-hemiacetals from Terminal Alkynes: Access to N,N-, N,S-, and N,O-Acetals.

A mild electron donor-acceptor complex-mediated approach for the synthesis of N-acyl-N,O-hemiacetals has been reported. The key feature of this protocol is that it allows for direct access to electrophilic N-acylimines at room temperature without prefunctionalization of the hydroxyl group. The in situ generated N-acylimine can react with different nucleophiles, viz., alcohols, thiols, and nitriles, to afford a diverse range of scaffolds such as N,O-, N,S-, and N,N-acetals.

Photoredox-Promoted Selective Synthesis of C-5 Thiolated 2-Aminothiazoles from Terminal Alkynes.

A mild photoredox approach enabling the first one-step synthesis of thiolated 2-aminothiazoles has been reported. Notably, the incorporation of thio group on electron-rich heteroarenes such as aminothiazoles via conventional nucleophilic aromatic substitution (SNAr) presents a significant challenge owing to polarity mismatch. Herein, we present a remarkable site-selective installation of thio group at the C-5 position of the electron-rich aminothiazole skeleton and successfully used them for the postfunctionalization of drugs and natural products.

Hybrid Polymer Composite of Prussian Red Doped Polythiophene for Adsorptive Wastewater Treatment Application.

Coordination compounds as dopants to conducting polymers combine desirable properties of individual components for a synergistic effect. Prussian red (PR) a low spin iron (III) coordination compound was doped in polythiophene (PTP) matrix to explore propensity of this inorganic-organic hybrid composite material towards wastewater treatment. PR doping was observed to improve mechano, thermal, electrical, and photocatalytic attributes of pure PTP. PTP/PR composite characterization was attempted using the powder X-ray diffraction, TEM, TGA, FTIR, BET analysis and UV-Visible spectroscopy. Optimization of adsorption conditions, adsorbent regeneration, adsorption thermodynamics studies of PTP/PR were carried out using malachite green (MG) dye as a model system. Under optimized conditions 92% MG dye adsorption was observed over 20 mg PTP/PR nanocomposite in 20 minutes at pH 7. PTP/PR nanocomposite also demonstrated a complimentary performance with real wastewater samples. Thermodynamic studies indicate spontaneous process with electrostatic attraction as the predominant noncovalent interaction. This study highlights designing catalysts capable of synergistic adsorption and photocatalytic activities for effective wastewater treatment.

Synthesis of 1,2-oxazetidines with a free -NH group via photoredox catalysis.

A photoredox approach enabling one-step synthesis of oxazetidines with a free -NH group via the combined use of alkyne, thiophenol, and azide has been reported. The synthesized oxazetidine with the free -NH group was stable enough for various late-stage transformations such as methylation, acetylation, tosylation, and ring-opening reaction to afford synthetically useful α-aminoketones.

Photoredox Catalyzed Thioformylation of Terminal Alkynes Using Nitromethane as a Formyl Source.

A photoredox thioformylation of terminal alkynes using nitromethane as a formyl anion equivalent, thereby leading to the synthesis of (E)-1,2-difunctionalized acrylaldehyde, has been described. The current strategy introduces an adaptable aldehyde function across an alkyne and offers a new route to synthesizing α-alkyl/aryl aldehydes.

Multidimensional Role of Silicon to Activate Resilient Plant Growth and to Mitigate Abiotic Stress.

Sustainable agricultural production is critically antagonistic by fluctuating unfavorable environmental conditions. The introduction of mineral elements emerged as the most exciting and magical aspect, apart from the novel intervention of traditional and applied strategies to defend the abiotic stress conditions. The silicon (Si) has ameliorating impacts by regulating diverse functionalities on enhancing the growth and development of crop plants. Si is categorized as a non-essential element since crop plants accumulate less during normal environmental conditions. Studies on the application of Si in plants highlight the beneficial role of Si during extreme stressful conditions through modulation of several metabolites during abiotic stress conditions. Phytohormones are primary plant metabolites positively regulated by Si during abiotic stress conditions. Phytohormones play a pivotal role in crop plants' broad-spectrum biochemical and physiological aspects during normal and extreme environmental conditions. Frontline phytohormones include auxin, cytokinin, ethylene, gibberellin, salicylic acid, abscisic acid, brassinosteroids, and jasmonic acid. These phytohormones are internally correlated with Si in regulating abiotic stress tolerance mechanisms. This review explores insights into the role of Si in enhancing the phytohormone metabolism and its role in maintaining the physiological and biochemical well-being of crop plants during diverse abiotic stresses. Moreover, in-depth information about Si's pivotal role in inducing abiotic stress tolerance in crop plants through metabolic and molecular modulations is elaborated. Furthermore, the potential of various high throughput technologies has also been discussed in improving Si-induced multiple stress tolerance. In addition, a special emphasis is engrossed in the role of Si in achieving sustainable agricultural growth and global food security.

Organoselenium Compounds as Acetylcholinesterase Inhibitors: Evidence and Mechanism of Mixed Inhibition.

Acetylcholinesterase (AChE) inhibitors are actively used for the effective treatment of Alzheimer's disease. In recent years, the neuroprotective effects of organoselenium compounds such as ebselen and diselenides on the AChE activity have been investigated as potential therapeutic agents. In this work, we have carried out systematic kinetic and intrinsic fluorescence assays in combination with docking and molecular dynamics (MD) simulations to elucidate the molecular mechanism of the mixed inhibition of AChE by ebselen and diphenyl diselenide (DPDSe) molecules. Our MD simulations demonstrate significant heterogeneity in the binding modes and allosteric hotspots for DPDSe on AChE due to non-specific interactions. We have further identified that both ebselen and DPDSe can strongly bind around the peripheral anionic site (PAS), leading to non-competitive inhibition similar to other PAS-binding inhibitors. We also illustrate the entry of the DPDSe molecule into the gorge through a "side door", which offers an alternate entry point for AChE inhibitors as compared to the usual substrate entry point of the gorge. Together with results from experiments, these simulations provide mechanistic insights into the mixed type of inhibition for AChE using DPDSe as a promising inhibitor for AChE.

In vitro and In silico Evaluation of Structurally Diverse Benzyl-pyrrolidine-3-ol Analogues as Apoptotic Agents via Caspase Activation.

The activation of caspases is central to apoptotic process in living systems. Defects in apoptosis have been implicated with carcinogenesis. Need to develop smart agents capable of inducing apoptosis in tumor cells is obvious. With this motive, diversity oriented synthesis of 1-benzylpyrrolidin-3-ol analogues was envisaged. The multi component Ugi reaction synthesized library of electronically diverse analogues was explored for cytotoxic propensity towards a panel of human cancer cell lines at 10 µM. The lead compounds exhibit a selective cytotoxicity towards HL-60 cells as compared to cell lines derived from solid tumors. Besides, their milder cytotoxic effect on non-cancerous cell lines reaffirm their selective action towards cancer cells only. The lead molecules were tested for their ability to target caspase-3, as a vital protease triggering apoptosis. The lead compounds were observed to induce apoptosis in HL-60 cells around 10 µM concentration. The lead compounds exhibited various non-covalent supra type interactions with caspase-3 key residues around the active site. The binding ability of lead compounds with caspase-3 was studied via molecular docking and molecular dynamic (MD) simulations. MD simulations indicated the stability of compound-caspase-3 complex throughout the 50 ns simulation run. The stability and bio-availability of the lead compounds under physiological conditions was assessed by their interaction with Bovine Serum Albumin (BSA) as model protein. BSA interactions of lead compounds were studied by various bio-physical methods and further substantiated with in silico MD simulations.