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Item Photoinduced C(sp3)-H Chalcogenation of Amide Derivatives and Ethers via Ligand-to-Metal Charge-Transfer(American Chemical Society, 2022) Niu, Ben; Sachidanandan, Krishnakumar; Cooke, Maria Victoria; Casey, Taylor E.; Laulhé, Sébastien; Chemistry and Chemical Biology, School of ScienceA photoinduced, iron(III) chloride-catalyzed C-H activation of N-methyl amides and ethers leads to the formation of C-S and C-Se bonds via a ligand-to-metal charge transfer (LMCT) process. This methodology converts secondary and tertiary amides, sulfonamides, and carbamates into the corresponding amido-N,S-acetal derivatives in good yields. Mechanistic work revealed that this transformation proceeds through a hydrogen atom transfer (HAT) involving chlorine radical intermediates.Item Prolonged Exposure to Remdesivir Inhibits the Human Ether-A-Go-Go-Related Gene Potassium Current(Wolters Kluwer, 2023-09-01) Amarh, Enoch; Tisdale, James E.; Overholser, Brian R.; Pharmacology and Toxicology, School of MedicineRemdesivir, approved for the treatment of COVID-19, has been associated with heart-rate corrected QT interval (QTc) prolongation and torsade de pointes in case reports. However, data are conflicting regarding the ability of remdesivir to inhibit the human ether-a-go-go-related gene (hERG) -related current. The objective of this study was to investigate the effects remdesivir and its primary metabolite, GS-441524, on hERG-related currents. Human embryonic kidney 293 cells stably expressing hERG were treated with various concentrations of remdesivir and GS-441524. The effects of acute and prolonged exposure on hERG-related current were assessed using whole-cell configuration of voltage-clamp protocols. Acute exposure to remdesivir and GS-441524 had no effect on hERG currents and the half-activation voltage (V 1/2 ). Prolonged treatment with 100 nM and 1 µM remdesivir significantly reduced peak tail currents and hERG current density. The propensity for remdesivir to prolong QTc intervals and induce torsade de pointes in predisposed patients warrants further investigation.