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The construction of quaternary carbon centers at the para-position of benzamide derivatives is of significant importance for the synthesis of pharmaceutical agents and their key precursors. Such structural motifs can serve directly as small-molecule targeted compounds or be further elaborated into complex ligand architectures to meet diverse pharmacological requirements. However, achieving high selectivity in the formation of these quaternary carbon centers remains a long-standing challenge. We herein report a method for the para-selective construction of quaternary carbon centers on benzamide derivatives via iron catalysis. This transformation proceeds at room temperature using benzamide derivatives and tertiary alkyl Grignard reagents. By employing a catalytic system comprising inexpensive iron(II) salt and tert-butylmagnesium chloride, this method enables the introduction of sterically demanding tertiary alkyl groups at the para-position with high regioselectivity, effectively suppressing common side reactions such as alkyl group isomerization or ortho-alkylation. This approach exhibits a diverse range of applicable aryl amides, though N-alkyl substrates are not tolerated.

Microplastics (MPs) have become an emerging contaminant of concern, yet their presence in ocular formulations and products remains poorly understood. This study employed a dual-method approach (water dilution and Fenton digestion) coupled with micro-FTIR analysis to investigate the MP contamination in 21 commercial eyedrop products in Malaysia. Our findings demonstrate widespread contamination, with 81% of samples containing detectable MPs. They are predominantly composed of polystyrene (PS) (52%), polyamide (PA) (19%), and polyethylene (PE) (14%). The particle abundance varied significantly across classes of eyedrops. Specifically, one lubricant eyedrop reported a mean concentration of 3 particles/ml, representing the highest concentration among all categories. Morphological characterization revealed diverse particle shapes, including irregular fragments (most common), fibers, and pellets. The area of MPs detected ranged between 369 to 36,388 µm². The pollution load assessment indicated that the lubricant eyedrops showed extreme contamination levels (MPCF = 15). The calculated daily microplastic exposure (DME) suggests a potential emission of up to 2.704 million MP particles daily among lubricant users in the general Malaysian population. Glaucoma patients in rural areas are potentially exposed to 0.049 million particles daily and urban areas at 0.137 million. These results provide the first evidence of MP contamination in eyedrops in Malaysia, highlighting a previously unrecognized route of human exposure. The findings emphasize the need for improved manufacturing standards and regulatory oversight to minimize plastic contamination in ocular products. While these findings suggest MPs are present in many eyedrop products, further research would be needed to understand any potential health implications.

This study reports large microplastics found in Lake Victoria through an analytical workflow that combines the complementary methods stereomicroscopy, micro-Fourier transform infrared (µ-FTIR) spectroscopy and pyrolysis gas chromatography-mass spectrometry (Pyr-GC-MS) for the quantification of 11 environmentally relevant microplastic polymers. Algae-rich surface water samples (n = 18) were trawled using a 0.3 mm manta net from Lake Victoria, the world's largest tropical lake. Stereomicroscopy as a determinant analytical technique detected 191 particles, which were primarily blue fragments and fibres. Polyethylene and polypropylene were the dominant polymers identified by µ-FTIR. Pyr-GC-MS allowed the detection and quantification of microplastics (MPs) with LOD and LOQ of 0.01-14.7 µg and 0.03-49.1 µg. Polyethylene (0.058-0.34 µg/L), polypropylene (0.024 µg/L and 0.043 µg/L), nylon 6 (0.0051-0.064 µg/L), nylon 66 (0.0022-0.084 µg/L), poly(ethylene terephthalate) (0.0029-0.027 µg/L) and poly(methyl methacrylate) (0.0036 µg/L) were quantified. µ-FTIR was found to be suitable for the identification of the most abundant polymers in the 0.3-4.9 mm size range whereas Pyr-GC-MS afforded the quantification of seven polymers, most of which were not detected by µ-FTIR. This complementary workflow gave a wider perspective on MP loading, providing both polymer concentrations and physical characteristics (sizes, colours, forms and count) of the MPs.

ATP-citrate lyase (ACLY) is an upstream enzyme involved in fatty acid synthesis, cholesterol metabolism, and histone acetylation. Therefore, selective inhibition of ACLY represents a promising strategy for the treatment of dyslipidemia and various cancers. Recently, the cryo-EM structure of the ACLY complex with the allosteric inhibitor NDI-091143 has been reported, providing an opportunity to discover new potent inhibitors of this emerging target. In this in silico study, we report structure-based models that were rigorously developed and evaluated using reported allosteric inhibitors of ACLY. The pharmacophore model (ROC-AUC = 0.85, GH = 0.78, and EF_1% = 49.18) and the molecular docking model (RMSD_redock = 0.884 Å and ROC-AUC = 0.95) were applied to virtual screening of the ZINC15 library. During hit selection for further evaluation by molecular dynamics simulations, post-docking analysis was performed based on docking scores (ΔG_dock) alone and in combination with the Tanimoto similarity coefficient of protein-ligand interaction fingerprints (Tc_IFP). The combined ΔG_dock and Tc_IFP approach enabled the identification of four out of five selected top hits with binding free energies more favorable than that of the reference compound NDI-091143, supporting their potential as allosteric ACLY inhibitors. These compounds may be subjected to further experimental evaluation to confirm their biological activity. In addition, the workflow developed in the present study may provide a basis for future discovery and optimization of allosteric ACLY inhibitors.