Catalytic and Atom‐Economic C −C Bond Formation: Alkyl Tantalum Ureates for Hydroaminoalkylation

Atom‐economic and regioselective C ?C bond formation has been achieved by rapid C?H alkylation of unprotected secondary arylamines with unactivated alkenes. The combination of Ta(CH₂SiMe₃)₃Cl₂, and a ureate N,O‐chelating‐ligand salt gives catalytic systems prepared in situ that can realize high yields of β‐alkylated aniline derivatives from either terminal or internal alkene substrates. These new catalyst systems realize C?H alkylation in as little as one hour and for the first time a 1:1 stoichiometry of alkene and amine substrates results in high yielding syntheses of isolated amine products by simple filtration and concentration.     

Modifying the Steric Properties in the Second Coordination Sphere of Designed Peptides Leads to Enhancement of Nitrite Reductase Activity

Protein design is a useful strategy to interrogate the protein structure‐function relationship. We demonstrate using a highly modular 3‐stranded coiled coil (TRI‐peptide system) that a functional type 2 copper center exhibiting copper nitrite reductase (NiR) activity exhibits the highest homogeneous catalytic efficiency under aqueous conditions for the reduction of nitrite to NO and H₂O. Modification of the amino acids in the second coordination sphere of the copper center increases the nitrite reductase activity up to 75‐fold compared to previously reported systems. We find also that steric bulk can be used to enforce a three‐coordinate Cu^I in a site, which tends toward two‐coordination with decreased steric bulk. This study demonstrates the importance of the second coordination sphere environment both for controlling metal‐center ligation and enhancing the catalytic efficiency of metalloenzymes and their analogues.     

Functional Hydride Transfer by a Thiolate‐Containing Model of Mono‐Iron Hydrogenase featuring an Anthracene Scaffold

We report the synthesis, X‐ray structure and functional biomimetic activity of a model complex of mono‐iron hydrogenase (Hmd). To achieve the desired biomimetic fac‐CNS(thiolate) ligation motif, an anthracene framework is used to provide the requisite donors in a single chelate. A bulky aryl thiolate (ortho dimethylphenyl) is included to achieve mononuclearity. In addition to exhibiting structural (X‐ray) and spectroscopic (NMR, IR) similarity to the enzyme, the complex is competent for H₂ activation (heterolysis) and hydride transfer to a model substrate—mimicking the functional behavior of the enzyme in a biomimetic CNS coordination sphere for the first time.     

Active Intracellular Delivery of a Cas9/sgRNA Complex Using Ultrasound‐Propelled Nanomotors

Direct and rapid intracellular delivery of a functional Cas9/sgRNA complex using ultrasound‐powered nanomotors is reported. The Cas9/sgRNA complex is loaded onto the nanomotor surface through a reversible disulfide linkage. A 5 min ultrasound treatment enables the Cas9/sgRNA‐loaded nanomotors to directly penetrate through the plasma membrane of GFP‐expressing B16F10 cells. The Cas9/sgRNA is released inside the cells to achieve highly effective GFP gene knockout. The acoustic Cas9/sgRNA‐loaded nanomotors display more than 80 % GFP knockout within 2 h of cell incubation compared to 30 % knockout using static nanowires. More impressively, the nanomotors enable highly efficient knockout with just 0.6 nm of the Cas9/sgRNA complex. This nanomotor‐based intracellular delivery method thus offers an attractive route to overcome physiological barriers for intracellular delivery of functional proteins and RNAs, thus indicating considerable promise for highly efficient therapeutic applications.     

Crystalline‐Sponge‐Based Structural Analysis of Crude Natural Product Extracts

Characterization of complex natural product mixtures to the absolute structural level of their components often requires significant amounts of starting materials and lengthy purification process, followed by arduous structure elucidation efforts. The crystalline sponge (CS) method has demonstrated utility in the absolute structure elucidation of isolated organic compounds at miniscule quantities compared to conventional methods. In this work, we developed a new CS‐based workflow that greatly expedites the in‐depth structural analysis of crude natural product extracts. Using a crude extract of the red alga Laurencia pacifica, we showed that CS affinity screening prior to compound isolation enables prioritization of analytes present in the extract, and we subsequently resolved the molecular structures of six sesquiterpenes with stereochemical clarity from around 10 mg crude extract. This study demonstrates a new chemotyping workflow that can greatly accelerate natural product discovery from complex samples.     

Glycosyl‐Substituted Dicarboxylates as Detergents for the Extraction,Overstabilization, and Crystallization of Membrane Proteins

To tackle the problems associated with membrane protein (MP) instability in detergent solutions, we designed a series of glycosyl‐substituted dicarboxylate detergents (DCODs) in which we optimized the polar head to clamp the membrane domain by including, on one side, two carboxyl groups that form salt bridges with basic residues abundant at the membrane–cytoplasm interface of MPs and, on the other side, a sugar to form hydrogen bonds. Upon extraction, the DCODs 8 b , 8 c , and 9 b preserved the ATPase function of BmrA, an ATP‐binding cassette pump, much more efficiently than reference or recently designed detergents. The DCODs 8 a , 8 b , 8 f , 9 a , and 9 b induced thermal shifts of 20 to 29 °C for BmrA and of 13 to 21 °C for the native version of the G‐protein‐coupled adenosine receptor A_2AR. Compounds 8 f and 8 g improved the diffraction resolution of BmrA crystals from 6 to 4 Å. DCODs are therefore considered to be promising and powerful tools for the structural biology of MPs.     

Tunable and Photoswitchable Chemically Induced Dimerization for Chemo‐optogenetic Control of Protein and Organelle Positioning

The spatiotemporal dynamics of proteins and organelles play an important role in controlling diverse cellular processes. Optogenetic tools using photosensitive proteins and chemically induced dimerization (CID), which allow control of protein dimerization, have been used to elucidate the dynamics of biological systems and to dissect the complicated biological regulatory networks. However, the inherent limitations of current optogenetic and CID systems remain a significant challenge for the fine‐tuning of cellular activity at precise times and locations. Herein, we present a novel chemo‐optogenetic approach, photoswitchable chemically induced dimerization (psCID), for controlling cellular function by using blue light in a rapid and reversible manner. Moreover, psCID is tunable; that is, the dimerization and dedimerization degrees can be fine‐tuned by applying different doses of illumination. Using this approach, we control the localization of proteins and positioning of organelles in live cells with high spatial (μm) and temporal (ms) precision.     

A Robust 3D Cage‐like Ultramicroporous Network Structure with High Gas‐Uptake Capacity

A three‐dimensional (3D) cage‐like organic network (3D‐CON) structure synthesized by the straightforward condensation of building blocks designed with gas adsorption properties is presented. The 3D‐CON can be prepared using an easy but powerful route, which is essential for commercial scale‐up. The resulting fused aromatic 3D‐CON exhibited a high Brunauer–Emmett–Teller (BET) specific surface area of up to 2247 m² g^?1. More importantly, the 3D‐CON displayed outstanding low pressure hydrogen (H₂, 2.64 wt %, 1.0 bar and 77 K), methane (CH₄, 2.4 wt %, 1.0 bar and 273 K), and carbon dioxide (CO₂, 26.7 wt %, 1.0 bar and 273 K) uptake with a high isosteric heat of adsorption (H₂, 8.10 kJ mol^?1; CH₄, 18.72 kJ mol^?1; CO₂, 31.87 kJ mol^?1). These values are among the best reported for organic networks with high thermal stability (ca. 600 °C).     

Distinct Electron Conductance Regimes in Bacterial Decaheme Cytochromes

Shewanella oneidensis MR‐1 gains energy by extracellular electron transfer to solid surfaces. They employ c‐type cytochromes in two Mtr transmembrane complexes, forming a multiheme wire for electron transport across the cellular outer membrane. We investigated electron‐ and hole‐transfer mechanisms in the external terminal of the two complexes, MtrC and MtrF. Comparison of computed redox potentials with previous voltammetry experiments in distinct environments (isolated and electrode‐bound conditions of PFV or in vivo) suggests that these systems function in different regimes depending on the environment. Analysis of redox potential shifts in different regimes indicates strong coupling between the hemes via an interplay between direct Coulomb and indirect interactions through local structural reorganization. The latter results in the screening of Coulomb interactions and explains poor correlation of the strength of the heme‐to‐heme interactions with the distance between the hemes.