Structures of the human lysosomal K+ channel transmembrane protein 175 (TMEM175) in open and closed states revealed a novel architecture lacking the canonical K+ selectivity filter motif present in previously known K+ channel structures. A hydrophobic constriction composed of four isoleucine residues was resolved in the pore and proposed to serve as the gate in the closed state, and to confer ion selectivity in the open state. Here, we achieve higher-resolution structures of the open and closed states and employ molecular dynamics simulations to analyze the conducting properties of the putative open state, demonstrating that it is permeable to K+ and, to a lesser degree, also Na+. Both cations must dehydrate significantly to penetrate the narrow hydrophobic constriction, but ion flow is assisted by a favorable electrostatic field generated by the protein that spans the length of the pore. The balance of these opposing energetic factors explains why permeation is feasible, and why TMEM175 is selective for K+ over Na+, despite the absence of the canonical selectivity filter. Accordingly, mutagenesis experiments reveal an exquisite sensitivity of the channel to perturbations that mitigate the constriction. Together, these data reveal a novel mechanism for selective permeation of ions by TMEM175 that is unlike that of other K+ channels.

The expanding scope of chemical reactions applied to nucleic acids has diversified the design of nucleic acid-based technologies that are essential to medicinal chemistry and chemical biology. Among chemical reactions, visible light photochemical reaction is considered a promising tool that can be used for the manipulations of nucleic acids owing to its advantages, such as mild reaction conditions and ease of the reaction process. Of late, inspired by the development of visible light-absorbing molecules and photocatalysts, visible light-driven photochemical reactions have been used to conduct various molecular manipulations, such as the cleavage or ligation of nucleic acids and other molecules as well as the synthesis of functional molecules. In this review, we describe the recent developments (from 2010) in visible light photochemical reactions involving nucleic acids and their applications in the design of nucleic acid-based technologies including DNA photocleaving, DNA photoligation, nucleic acid sensors, the release of functional molecules, and DNA-encoded libraries.

The Pd‐catalyzed γ‐position sp3−C−H arylation of primary amines bearing an aliphatic chain or cycloalkyl substituent and related mechanistic studies are disclosed. 3‐Bromo‐2‐hydroxybenzaldehyde plays a key role in γ‐position sp3−C−H arylation as a transient directing group (TDG) to assist the regio‐ and stereoselective C−H activation of a Pd catalyst, and the development of a tandem reaction to transform 1°‐amines into γ‐aryl‐substituted ketones demonstrates synthetic utility. Density functional theory (DFT)‐based calculations revealed the detailed reaction mechanism and the origins of the high selectivity (γ‐position and cis‐only). The X‐ray crystal structure of the isolated endo‐palladacycle intermediate supported the DFT results, and a kinetic isotope experiment confirmed the results of DFT calculations indicating that the C−H activation step via simultaneous palladation and deprotonation is rate‐determining.

Positively charged aromatic quaternary ammonium and aliphatic quaternary ammonium groups were successfully installed in metal-organic frameworks (MOFs) for hydroxide conductivity studies. Two representative solid-state MOF functionalization strategies, post-synthetic covalent modification...

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