A Chemical Proteomic Probe for the Mitochondrial Pyruvate Carrier Complex

Target engagement assays are crucial for establishing the mechanism‐of‐action of small molecules in living systems. Integral membrane transporters can present a challenging protein class for assessing cellular engagement by small molecules. The chemical proteomic discovery of alpha‐chloroacetamide (αCA) compounds that covalently modify cysteine‐54 (C54) of the MPC2 subunit of the mitochondrial pyruvate carrier (MPC) is presented. This finding is used to create an alkyne‐modified αCA, YY4‐yne, that serves as a cellular engagement probe for MPC2 in click chemistry‐enabled western blotting or global mass spectrometry‐based proteomic experiments. Studies with YY4‐yne revealed that UK‐5099, an alpha‐cyanocinnamate inhibitor of the MPC complex, engages MPC2 with remarkable selectivity in human cells. These findings support a model where UK‐5099 inhibits the MPC complex by binding to C54 of MPC2 in a covalent reversible manner that can be quantified in cells using the YY4‐yne probe.     

Room‐Temperature Phosphorescence‐active Boronate Particles: Characterization and Ratiometric Afterglow‐sensing Behavior by Surface Grafting of Rhodamine B

We found that boronate particles ( BP ), as a self‐assembled system prepared by sequential dehydration of benzene‐1,4‐diboronic acid with pentaerythritol, showed greenish room‐temperature phosphorescence (RTP). This emission was observed in both solid and dispersion state in water. To understand the RTP properties, X‐ray crystallographic analysis, and density functional theory (DFT) and time‐dependent DFT at M06‐2X/6‐31G(d,p) level were performed using 3,9‐dibenzo‐2,4,8,10‐tetraoxa‐3,9‐diboraspiro[5.5]undecane ( 1 ) as a model compound. Our interest in functionalizing the RTP‐active particles led us to graft Rhodamine B onto their surface. The resulting system emitted a dual afterglow via a Förster‐type resonance energy transfer process from the BP in the excited triplet state to Rhodamine B acting as an acceptor fluorophore. This emission behavior was used for ratiometric afterglow sensing of water content in THF with a detection limit of 0.28 %, indicating that this study could pave the way for a new strategy for developing color‐variable afterglow chemosensors for various analytes.     

Control of the Single‐Molecule Magnet Behavior of Lanthanide‐Diarylethene Photochromic Assemblies by Irradiation with Light

Lanthanide‐based extended coordination frameworks showing photocontrolled single‐molecule magnet (SMM) behavior were prepared by combining highly anisotropic Dy^III and Ho^III ions with the carboxylato‐functionalized photochromic molecule 1,2‐bis(5‐carboxyl‐2‐methyl‐3‐thienyl)perfluorocyclopentene (H₂dae), which acts as a bridging ligand. As a result, two new compounds of the general formula [{Ln^III₂(dae)₃(DMSO)₃(MeOH)} ? 10 M eOH]_n (M=Dy for 1 a and Ho for 2 ) and two additional pseudo‐polymorphs [{Dy^III₂(dae)₃(DMSO)₃(H₂O)} ? x MeOH]_n ( 1 b ) and [{Dy^III₂(dae)₃(DMSO)₃(DMSO)} ? x MeOH]_n ( 1 c ) were obtained. All four compounds have 2D coordination‐layer topologies, in which carboxylate‐bridged Ln₂ units are linked together by dae^2? anions into grid‐like frameworks. All four compounds exhibited a strong reversible photochromic response to UV/Vis light. Moreover, both 1 a and 2 show field‐induced SMM behavior. The slow magnetic relaxation of 1 a is influenced by the photoisomerization reaction leading to the observation of the cross‐effect: photocontrolled SMM behavior.     

Hydrophobic Modification of Pd/SiO2@Single‐Site Mesoporous Silicas by Triethoxyfluorosilane: Enhanced Catalytic Activity and Selectivity for One‐Pot Oxidation

To enhance the catalytic activity in a selective one‐pot oxidation using in‐situ generated H₂O₂, a hydrophobically modified core–shell catalyst was synthesized by means of a simple silylation reaction using the fluorine‐containing silylation agent triethoxyfluorosilane (TEFS, SiF(OEt)₃). The catalyst consisted of a Pd‐supported silica nanosphere and a mesoporous silica shell containing isolated Ti^IV and F ions bonded with silicon (Si?F bond). Structural analyses using XRD and N₂ adsorption–desorption suggested that the mesoporous structure and large surface area of the mesoporous shells were retained even after the modification. During the one‐pot oxidation of sulfide, catalytic activity was enhanced significantly by increasing the amount of fluorine in the shell. A hydrophobic surface enhanced adsorption of the hydrophobic reactant into the mesopore, while the less hydrophobic oxygenated products efficiently diffused into the outside of the shell, which improved the catalytic activity and selectivity. In addition, the present methodology can be used to enhance the catalytic activity and selectivity in the one‐pot oxidation of cyclohexane by using an Fe‐based core–shell catalytic system.     

New Procedure for the Synthesis of 2-Alkylbenzimidazoles

Simple, economical, and environmentally friendly method to synthesize 2-alkylbenzimidazoles was developed by modifying the conventional method between o-phenylenediamine and aldehyde.     

Simultaneous Assessment of Kinetic,Site‐Specific,and Structural Aspects of Enzymatic Protein Phosphorylation

Protein phosphorylation is a widespread process forming the mechanistic basis of cellular signaling. Up to now, different aspects, for example, site‐specificity, kinetics, role of co‐factors, and structure–function relationships have been typically investigated by multiple techniques that are incompatible with one another. The approach introduced here maximizes the amount of information gained on protein (complex) phosphorylation while minimizing sample handling. Using high‐resolution native mass spectrometry on intact protein (assemblies) up to 150 kDa we track the sequential incorporation of phosphate groups and map their localization by peptide LC‐MS/MS. On two model systems, the protein kinase G and the interplay between Aurora kinase A and Bora, we demonstrate the simultaneous monitoring of various aspects of the phosphorylation process, namely the effect of different cofactors on PKG autophosphorylation and the interaction of AurA and Bora as both an enzyme–substrate pair and physical binding partners.     

Influence of annealing on the spatial distribution of thermoelectric properties in bismuth-telluride specimens

A p-type (Bi_0.25Sb_0.75)₂Te₃ specimen doped with 8 wt. % excess Te alone and an n-type Bi₂(Te_0.94Se_0.06)₃ specimen codoped with 0.017 wt. % Te and 0.068 wt. % I were grown by the Bridgeman method and were cut into a parallelepiped of 5×5×15 mm³, where the length of 15 mm is parallel to the freezing direction. Their local Seebeck coefficient α_ℓ and local electrical resistivity ϱ_ℓ were measured before and after annealing at a scan step of 1 mm along the freezing direction of the specimen, where annealing was done at 673 K for 2 h in vacuum. The specimen was mounted on an X–Y stage and the temperature difference between two probes set at an interval of 1 mm apart was approximately 2.6 K and measured with an accuracy of 0.1 K. The ϱ_ℓ of the as-grown and annealed specimens changed more significantly from place to place than their α_ℓ, so that the effect of annealing on the local power factor P_ℓ (=α_ℓ ²/ϱ_ℓ) was not uniform throughout the specimen surface. Such a spatial variation in P_ℓ is considered to result mainly from the spatial variation in ϱ_ℓ which originates from only a slight deviation of the melt composition from the stoichiometry inside a specimen, and also from a difference in the degree of alignment of the c planes of grains inside a specimen. The maximum P_ℓ (=α_ℓ ²/ϱ_ℓ) of the annealed p- and n-type specimens reached surprisingly high values of 7.78 and 8.93 mW/K² m, respectively, which correspond to being about twice as large as the macroscopic P values obtained by conventional methods. PACS 72.15.Jf; 84.60.Rb; 85.30.De