Meglumine‐based Sustainable Three‐component Deep Eutectic Solvent Applicable for the Synthesis of Pyrazolo[5,1‐b]quinazoline‐3‐carboxylates as a Sensing Probe for Cu2+ Ions

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Meglumine-based Sustainable Three-component Deep Eutectic Solvent Applicable for the Synthesis of Pyrazolo[5,1-b]quinazoline-3-carboxylates as a Sensing Probe for Cu2+ Ions

Design the low-cost, sustainable, and greener 3c-DES MegPAc catalyst as a synthetic tool. MegPAc serves the purpose to synthesize of pyrazolo[5,1-b]quinazoline-3-carboxylates and also worked profoundly in a gram-scale synthesis as well. Practically water is the only green waste though protocols demonstrated an admirable green chemistry credentials.


Abstract

An unprecedented meglumine-based three-component deep eutectic solvent (3c-DES) (MegPAc) was synthesized using meglumine, p-toluenesulfonic acid (PTSA), and acetic acid as a renewable, and non-toxic solvent. The exploitation of the MegPAc as an eco-friendly reaction media to construct a selective and sensitive small organic molecular sensing probe, namely, pyrazolo[5,1-b]quinazoline-3-carboxylates (PQCs) was executed. Captivatingly, the MegPAc served the dual role of solvent and catalyst, and it delivered the title components with 69–94 % yields within 67–150 minutes. Furthermore, a UV-visible study unfolds the selective detection of Cu2+ ions with our synthetic probe 4 ba and resulted in hypsochromic shift due to electrostatic interactions. Additionally, 1H NMR titration study and density functional theory (DFT) calculations were performed to attest the binding mechanism of sensing probe 4 ba and Cu2+ ions. Worthy of mention, this protocol unveils the efficacy of meglumine-based 3c-DES for the first time as a bio-renewable system to synthesize the PQCs.

Engineered RNA‐binding Proteins: Studying and Controlling RNA Regulation

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Engineered RNA-binding Proteins: Studying and Controlling RNA Regulation


Abstract

The complexity of eukaryotic organisms is intricately tied to transcriptome-level processes, notably alternative splicing and the precise modulation of gene expression through a sophisticated interplay involving RNA-binding protein (RBP) networks and their RNA targets. Recent advances in our understanding of the molecular pathways responsible for this control have paved the way for the development of tools capable of steering and managing RNA regulation and gene expression. The fusion between a rapidly developing understanding of endogenous RNA regulation and the burgeoning capabilities of CRISPR-Cas and other programmable RBP platforms has given rise to an exciting frontier in engineered RNA regulators. This review offers an overview of the existing toolkit for constructing synthetic RNA regulators using programmable RBPs and effector domains, capable of altering RNA sequence composition or fate, and explores their diverse applications in both basic research and therapeutic contexts.

Successive magnetic transitions and frustrated magnetism in Fe2(HPO3)3 ⋅ 4H2O

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Successive magnetic transitions and frustrated magnetism in Fe2(HPO3)3 ⋅ 4H2O

By combined magnetic susceptibility and specific heat measurements, we find two successive antiferromagnetic (AFM) transitions at ~9 K and ~5 K in Fe2(HPO3)3 ⋅ 4H2O. Through density functional theory (DFT) analysis we have calculated the AFM states. Two AFM configurations, namely AFM I and AFM II, are almost degenerate in energy and their competition leads to the two successive AFM phase transitions at low temperature, reflecting the frustrated magnetism in Fe2(HPO3)3 ⋅ 4H2O.


Abstract

We report the magnetic and optical properties of Fe2(HPO3)3 ⋅ 4H2O. By combined magnetic susceptibility and specific heat measurements, we find two antiferromagnetic (AFM) transitions (T N1=9 K, T N2=5 K) which originate from the AFM exchange interactions mediated by the (HPO3)2− anions. Compared with the non-hydrated compound Fe2(HPO3)3, the magnetic interaction strength and ordering temperature of Fe2(HPO3)3 ⋅ 4H2O are both reduced by a factor of ~2. Through density functional theory (DFT) analysis we find almost degenerate AFM states in Fe2(HPO3)3 ⋅ 4H2O which are close in energy. The competition of these AFM states might lead to the two successive AFM phase transitions at low temperature. The low ordering temperature as well as competing AFM states both imply frustrated magnetism in Fe2(HPO3)3 ⋅ 4H2O, probably originating from the complex competing AFM interactions. The optical properties of Fe2(HPO3)3 ⋅ 4H2O are also investigated by photoluminescence and infrared spectroscopies.

Ferrocene‐Boosted Nickel Sulfide Nanoarchitecture for Enhanced Alkaline Water Splitting

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Ferrocene-Boosted Nickel Sulfide Nanoarchitecture for Enhanced Alkaline Water Splitting

This study employs a one–step solvothermal approach to incorporate ferrocene (Fc) into nickel sulfide nanostructures, revealing exceptional electrocatalytic performance with an overpotential of 290 mV@10 mA cm−2, surpassing traditional nickel sulfide catalysts. Fc−NiS demonstrates superior charge transfer characteristics, attributed to ferrocene‘s effect on electrical conductivity. With remarkable stability over 25 hours, Fc−NiS emerges as a promising non-noble-based catalyst for sustainable hydrogen production.


Abstract

Enhanced electrocatalysts that are cost-effective, durable, and derived from abundant resources are imperative for developing efficient and sustainable electrochemical water–splitting systems to produce hydrogen. Therefore, the design and development of non–noble–based catalysts with more environmentally sustainable alternatives in efficient alkaline electrolyzers are important. This work reports ferrocene (Fc)-incorporated nickel sulfide nanostructured electrocatalysts (Fc−NiS) using a one–step facile solvothermal method for water–splitting reactions. Fc−NiS exhibited exceptional electrocatalytic activity under highly alkaline conditions, evident from its peak current density of 345 mA cm−2, surpassing the 153 mA cm−2 achieved by the pristine nickel sulfide (NiS) catalysts. Introducing ferrocene enhances electrical conductivity and facilitates charge transfer during water–splitting reactions, owing to the inclusion of iron metal. Fc−NiS exhibits a very small overpotential of 290 mV at 10 mA cm−2 and a Tafel slope of 50.46 mV dec−1, indicating its superior charge transfer characteristics for the three–electron transfer process involved in water splitting. This outstanding electrocatalytic performance is due to the synergistic effects embedded within the nanoscale architecture of Fc−NiS. Furthermore, the Fc−NiS catalyst also shows a stable response for the water–splitting reactions. It maintains a steady current density with an 87% retention rate for 25 hours of continuous operation, indicating its robustness and potential for prolonged electrolysis processes.

Crystal Engineering and Self‐Assembled Nanoring Formation with Purine‐CdII/HgII Supramolecular Frameworks

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Crystal Engineering and Self-Assembled Nanoring Formation with Purine-CdII/HgII Supramolecular Frameworks

A comparative crystallographic study of Cd(II)/Hg(II) complexes of isomeric purine rare tautomers and subsequent nanoring formation investigated by molecular dynamics simulations and transmission electron microscopy.


Abstract

We report three complexes of CdII and HgII with two purine rare tautomers, N9-(pyridin-2-ylmethyl)-N 6-methoxyadenine, L1 and N7-(pyridin-2-ylmethyl)-N 6-methoxyadenine, L2, highlighting diverse crystallographic signatures exhibited by them. Influence of substituents, binding sites, steric effects and metal salts on the different modes of binding enabled an insight into metal-nucleobase interactions. L1 interacted with two and three equivalents of Cd(NO3)2.4H2O and HgCl2, respectively, while L2 interacted with two equivalents of HgCl2, altogether leading to three different complexes (1 [C48H48Cd6N34O50], 2 [C12H12Cl4Hg2N6O] and 3 [C12H12Cl2HgN6O]) possessing varied dimensionality and stabilising interactions. The photoluminescent properties of these coordination frameworks have also been probed. Notably, nanoring-like structures were obtained, as a result of self-assembly of 3 when investigated by transmission electron microscopy, additionally supported by molecular dynamics simulations.

Structure‐Activity Relationships of 2‐(Arylthio)benzoic Acid FTO Inhibitors

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Structure-Activity Relationships of 2-(Arylthio)benzoic Acid FTO Inhibitors


Abstract

The biological role of the fat mass and obesity-associated protein (FTO) in the initiation and progress of acute myeloid leukemia (AML) has been elucidated, and several representative FTO inhibitors can markedly suppress the proliferation of AML cells. We previously developed FTO inhibitors including FB23. In this study, we adopted bioisosteric replacement of the intramolecular hydrogen bond in FB23 with a sulfur-oxygen interaction to generate a series of 2-(arylthio)benzoic acid FTO inhibitors and established their structure-activity relationships. Compound 8c was the most potent 2-(arylthio)benzoic acid FTO inhibitor with an IC50 value of 0.3±0.1 μM, which was comparable with that of FB23 in vitro. To enhance the antiproliferative effects in AML cell lines, we applied a prodrug strategy and prepared some esters. 7l, the methyl ester of 8l, exerted a superior inhibitory effect on a panel of AML cancer cell lines. Additionally, 7l treatment notably increased global m6A abundance in AML cells. Collectively, our data suggest that 2-(arylthio)benzoic acid may be a new lead compound for inhibition of FTO, and the prodrug analog exhibit potential in the treatment of AML.

Synthesis and biological evaluation of 3‐hydroxypyrazoles as aquaporin 9 inhibitors

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Synthesis and biological evaluation of 3-hydroxypyrazoles as aquaporin 9 inhibitors

A series of 3-hydroxypyrazole derivatives were synthesized and one of them, chosen based on in silico results, effectively inhibited aquaporin 9 (AQP9) in vitro.


Abstract

A series of 3-hydroxypyrazole derivatives have been synthesized by a base-promoted reaction of nitro-substituted donor–acceptor cyclopropanes with hydrazines. The synthesized compounds have been investigated for their ability to inhibit aquaporin 9 (AQP9) in rat Leydig cells (LC-540). The protein data bank structure for AQP9 was predicted using homology modeling; and the protein–ligand interaction for the synthesized hydroxyl pyrazole derivatives were analyzed using molecular modeling and docking studies. The results of in silico analyses showed that compound 5b had a higher binding affinity with AQP9 than other compounds. Further, in vitro studies conducted in LC-540 cells confirmed that compound 5b effectively inhibits AQP9. Hence, compound 5b may be used as an inhibitor in enhancing our understanding of AQP9 function, and in the treatment of several diseases.

Rational design of a circularly permuted flavin‐based fluorescent protein

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Flavin-based fluorescent proteins are oxygen-independent reporters that hold great promise for imaging anaerobic and hypoxic biological systems. In this study, we explored the feasibility of applying circular permutation, a valuable method for the creation of fluorescent sensors, to flavin-based fluorescent proteins. We used rational design and structural data to identify a suitable location for circular permutation in iLOV, a flavin-based reporter derived from A. thaliana. However, relocating the N- and C-termini to this position resulted in a significant reduction in fluorescence. This loss of fluorescence was reversible, however, by fusing dimerizing coiled coils at the new N- and C-termini to compensate for the increase in local chain entropy. Additionally, by inserting protease cleavage sites in circularly permuted iLOV, we developed two protease sensors and demonstrated their application in mammalian cells. In summary, our work establishes the first approach to engineer circularly permuted FbFPs optimized for high fluorescence and further showcases the utility of circularly permuted FbFPs to serve as a scaffold for sensor engineering.