Chemistry Letters, Ahead of Print.
Monthly Archives: September 2023
Pin-point surgery of proton-deuterium substitution to enhance polybenzimidazole thermoresistances
Chemistry Letters, Ahead of Print.
Influence of doped elements (O, K, and N) on melamine derived g-C3N4: insights into optical properties and photoactivity
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A novel cyclobutane-derived thiazole–thiourea hybrid with a potency against COVID-19 and tick-borne encephalitis: synthesis, characterization, and computational analysis
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[ASAP] A Multichannel Fluorescence Isothermal Amplification Device with Integrated Internet of Medical Things for Rapid Sensing of Pathogens through Deep Learning
Analytical Chemistry
DOI: 10.1021/acs.analchem.3c02973
Antimalarial Agents Targeting Plasmodium falciparum Carbonic Anhydrase: Towards Artesunate Hybrid Compounds with Dual Mechanism of Action
The development of new artesunate hybrid compounds containing benzenesulfonamide chemotypes as antimalarial agents through a dual mechanism of action: fast-acting ROS generation and long-lasting Plasmodium falciparum carbonic anhydrase (PfCA) inhibition.
Abstract
Malaria continues to be a major public health challenge worldwide and, as part of the global effort toward malaria eradication, plasmodium carbonic anhydrases (CAs) have recently been proposed as potential targets for malaria treatment. In this study, a series of eight hybrid compounds combining the Artesunate core with a sulfonamide moiety were synthesized and evaluated for their inhibition potency against the widely expressed human (h) CAs I, II and the isoform from P. falciparum (PfCA). All derivatives demonstrated high inhibition potency against PfCA, achieving a KI value in the sub-nanomolar range (0.35 nM). Two Compounds showed a selectivity index of 4.1 and 3.1, respectively, against this protozoan isoform compared to hCA II. Three Derivatives showed no cytotoxic effects on human gingival fibroblasts at 50 μM with a high killing rate against both P. falciparum and P. knowlesi strains with IC50 in the sub-nanomolar range, providing a wide therapeutic window. Our findings suggest that these compounds may serve as promising leads for developing new antimalarial drugs and warrant further investigation, including activity against antimalarial-resistant strains, mode of action studies, and in vivo efficacy assessment in preclinical mouse models of malaria.
Synthesis and Biological Profiling of Benzofuro‐Fused 7‐Deazapurine Nucleosides
A series of benzofuro-fused 7-deazapurine (6H-furo[2,3-e]pyrimido[4,5-b]indole) 2’-deoxyribo- and ribonucleosides was designed and synthesized. The synthesis of key 10-chloro-6H-furo[2,3-e]pyrimido[4,5-b]indole was based on the Negishi cross-coupling of iodobenzofurane with zincated 4,6-dichloropyrimidine followed by azidation and photochemical cyclization. Glycosylation of the heterocycle with either Hoffer’s chlorodeoxyribose or protected ribose followed by cross-coupling or substitution reactions at position 10 gave the desired two sets of final nucleosides that showed moderate to weak cytostatic activity and interesting fluorescence properties.
Equilibrium and Non‐equilibrium Reaction Schemes for Prebiotic Polymerization of Ribonucleotides
The RNA World theory for the origin of life requires polymers to be generated initially by abiotic reactions. Experiments have studied polymerization of 5′-monophosphates, 2′,3′-cyclic phosphates, and 5′-triphosphates. We consider theoretical models of polymerization in solution illustrating the differences between these cases. We consider (i) a basic model where all monomers undergo reversible joining and breaking; (ii) a model where 2′,3′-cyclic phosphates can join, and breaking regenerates the cyclic phosphate; (iii) a model where 5′-triphosphates can join irreversibly, in addition to the joining and breaking of 2′,3′-cyclic phosphates. In cases (i) and (ii) there is an equilibrium steady state with balance between making and breaking bonds. In case (iii) there is a circular reaction flux in which monomers are activated by an external phosphate source, activated monomers form polymers, and polymers break to release non-activated monomers. The mean length can be calculated as a function of concentration. In case (iii), the mean length switches from a low-concentration regime controlled by the 5′-triphosphates to a high-concentration regime controlled by the 2′,3′-cyclic phosphates. The circular reaction flux is reminiscent of a metabolism. If formation of 5’-triphosphates was already in place for RNA synthesis, ATP could subsequently been co-opted for metabolism.
Ag‐Doped Free‐Standing 2D TiO2 Sheets: Electronic, Optical, Magnetic, and Self‐Healing Behaviour
Beyond a critical doping level, Ag - 2D TiO2 sheets (ATO) are deemed to be a flexible transparent conductor, useful for visible-range functional photonic/optoelectronic devices/sensors, sunlight-sensitive catalysis, and light-activated resistive switching. Due to the lack of control of surface energy which often leads to the formation of structural defects and even dimensionality crossover (2D to 0D) of materials during doping reaction, it is challenging to obtain ATO with a controlled doping level. Gauging the urgency, therefore we report the surface energy-controlled synthesis of ATO employing liquid phase exfoliation of TiO2 and subsequent hydrothermal Ag-doping in the presence of Hexamethylenetetramine (HMTA). Electron microscopy and atomic force microscopy reveal ATO sheets with large lateral dimensions. 6-fold, 4-fold, and strain-mediated crystallographic phases of 2D ATO have been revealed by high-resolution electron imaging. Successful tuning of the band gap down to ~ 2 eV with Ag doping up to ~ 10% is obtained. Synthesized 2D ATO have been investigated for their electrical, optical, optoelectronic, photoluminescence, and ferromagnetic behaviour. Visible light-sensitive thermally/structurally robust semiconductor/conductor via tuneable doping will pave the way for their flexible as well as wearable device applications. Self-healing effect of AFM tip-generated mechanical stress has also been demonstrated.
Room Temperature Aerobic Oxidation of Amines to Nitriles over Ruthenium Oxide Supported on CeO2 Derived from MOFs
Heterogenous BPDC-RuO2-CeO2 catalyst derived from Ce-BPDC MOFs can successfully enable the oxidation of amines to nitriles under mild conditions (1 atm O2, H2O as a solvent, room temperature). The catalytic system has the good compatibility with benzylic and aliphatic amines. Lewis acid-base pair [Ru–O–Ce-Vö] formed by the combination of acidic oxygen vacancy and basic oxygen pair Ru–O–Ce on the surface of the catalyst is the key factor for the catalytic activity. The mechanical experiments indicate that amines adopt the step-by-step dehydrogenation process to nitriles in this transformation. Moreover, the catalyst could be recycled up to six times without the evident loss of catalytic activity and the change of morphology.