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.     

Syntheses and Structure of Hexacoordinated Selenium (λ6-Selane) and Tellurium (λ6-Tellane) Compounds

The first isolation of bis(2,2′-biphenylylene)dichloro- and difluoro-perchalcogenuranes, [12–Se–6(C4F2)] (λ⁶-selane); [12–Te–6(C4X2), X = Cl, F] (λ⁶-tellane) and the corresponding tellurane Te-oxide dimer [12–Te–6(C4O2)]₂, and their crystal and molecular structures are described. Furthermore, on the basis of the difference between the 3c-4e bonds of the dodecet species and that of the decet species a new molecular orbital concept has been proposed on the 3c-4e bond of perchalcogenurane species [12–M–6, M = chalcogen atoms].     

Polymerization of Methyl Methacrylate in the Presence of Imidazole Derivatives. Additive Effect of the Initiator Adduct and Copolymerization with Acrylamide

In the anionic polymerization of methyl methacrylate (MMA) induced by imidazole (Im), an Im‐MMA adduct forms as an initiator adduct in methanol at 30°C in an argon atmosphere by the equimolar reaction of Im with the MMA monomer. The additive effect of the adduct on the homopolymerization of MMA in tetrahydrofuran at 30°C was investigated by dilatometry. The existence of the adduct increased the duration of the propagation step without shortening the formation step of the initiator adduct. The H‐D exchange reaction of the adduct was observed in D₂O by ¹H NMR. Proton transfer of the MMA unit in the adduct was not observable until 45 h after initiation. The copolymerizability of MMA with acrylamide (AAm) induced by the Im catalyst in THF at 30°C was also investigated. It was found that the homo‐and copolymerizations proceeded at the same time. On the other hand, in the MMA homopolymerization system, the addition of AAm monomer during the initial propagation step yielded copolymer of MMA and AAm for near equimolar concentration of the charged monomers.     

Polymerization of Methyl Methacrylate in the Presence of Imidazole Derivatives. Kinetics and Polymer Structure

The kinetics of the polymerization of methyl methacrylate (MMA) in the presence of imidazole (Im), 2-methylimidazole (2MIm), or benz-imidazole (BIm) in tetrahydrofuran (THF) at 15–40°C was investigated by dilatometry. The rate of polymerization, R_p , was expressed by R_p = k[Im] [MMA]², where k = 3.0 × 10^?6 L²/(mol² s) in THF at 30°C. The overall activation energy, E_a , was 6.9 kcal/mol for the Im system and 7.3 kcal/mol for the 2MIm system. The relation between logR_p and 1 T was not linear for the BIm system. The polymers obtained were soluble in acetone, chloroform, benzene, and THF. The melting points of the polymers were in the range of 258–280°C. The ¹H-NMR spectra indicated that the polymers were made up of about 58–72% of syndiotactic structure. The polymerization mechanism is discussed on the basis of these results.     

Polymerizabilities of Several Polar Vinyl Monomers by Imidazole

Polymerizabilities of several polar vinyl monomers in the presence of imidazole (Im) have been studied in CDC1₃ and CD₃OD by NMR spectra. Acrylic acid formed a bimolecular adduct with Im as the initial adduct, while methacrylic acid was not obtained, On the other hand, methyl acrylate, methyl methacrylate (MMA), acrylamide (AAm), and acrylonitrile formed the initial adduct between Im and monomer, respectively. In these monomers, AAm and MMA gave each polymer in tetrahydrofuranat room temperature. The number-average molecular weight ([Mbar]_n) of AAm polymers was determined to be in the range of 1000 to 1500, and the [Mbar]_n of MMA polymers was found to be in the range of 2500 to 4500, The rate of polymerization R_p was expressed by the equations R_p = k[Im][AAm] and R_p = k[Im] [MMA]², respectively. The activation energy E_R was obtained by Arrheniuss's plots as E_R(AAm) = 9.6 kcal/mol and E_R(MMA) = 3.8 kcal/mol. These polymerization mechanisms are discussed on the basis of these results.     

Synthesis and Evaluation of Thiol Polymers

Thiol polymer, which is known as a reactive and functional polymer, is synthesized and evaluated quantitatively by the modified Ellman method. The synthesis was accomplished by 1) hydrolysis of an isothiouronium salt that is the adduct of 4‐chloromethylstyrene (CMS) homopolymer or CMS‐styrene (St) copolymer with thiourea; 2) hydrolysis of a precursor copolymer made from 4‐vinylbenzyl N‐ethyldithio‐carbamate (VBEC) and St or N‐vinyl‐2‐pyrrolidone (NVP); 3) solvolysis of an iminium salt polymer obtained from the reaction of CMS‐NVP copolymer with N,N‐dimethylthioformamide (TDMF). When a higher thiol content is desired, more severe hydrolysis conditions are required which however, also increase the loss of thiol. Hence, it is clear that the best synthesis of thiol polymers is Method 3. A quantitative yield of functional thiol polymer is obtained by this method, and the product is soluble in DMSO, DMF, and CHCI_3.     

Active Skeletal Ni Catalysts Prepared from an Amorphous Ni‐Zr Alloy in the Pre‐Crystallization State

Skeletal Ni catalysts were prepared from an amorphous Ni₄₀Zr₆₀ alloy (a‐NiZr) by heating at various temperatures under vacuum, followed by the selective extraction of Zr moieties by an HF treatment. Each sample was characterized by various spectroscopic methods, and the catalytic performance was tested in the hydrogenation of 1‐octene. The differences in preparation temperatures of a‐NiZr strongly affected the catalytic performance of the obtained catalysts, whereby those prepared from heated a‐NiZr in the pre‐crystallization state exhibited higher catalytic activity. Especially, moderate thermal treatment of a‐NiZr at a temperature slightly lower than that for its crystallization, that is, ～573 K, resulted in a significant enhancement of the catalytic activity. Such prepared skeletal Ni catalyst can also be used efficiently for hydrogen generation from aqueous hydrazine.     

Propagation of two longitudinal waves in a cancellous bone with the closed pore boundary

Ultrasound propagation in cancellous bone (porous media) under the condition of closed pore boundaries was investigated. A cancellous bone and two plate-like cortical bones obtained from a racehorse were prepared. A water-immersion ultrasound technique in the MHz range and a three-dimensional elastic finite-difference time-domain (FDTD) method were used to investigate the waves. The experiments and simulations showed a clear separation of the incident longitudinal wave into fast and slow waves. The findings advance the evaluation of bones based on the two-wave phenomenon for in vivo assessment.     

Scaling properties of universal tetramers

We evidence the existence of a universal correlation between the binding energies of successive four-boson bound states (tetramers), for large two-body scattering lengths (a), related to an additional scale not constrained by three-body Efimov physics. Relevant to ultracold atom experiments, the atom-trimer relaxation peaks for |a|→∞ when the ratio between the tetramer and trimer energies is ?4.6 and a new tetramer is formed. The new scale is also revealed for a < 0 by the prediction of a correlation between the positions of two successive peaks in the four-atom recombination process.     

Flame structure and flame spread rate over a solid fuel in partially premixed atmospheres

We have investigated the downward flame spread over a thin solid fuel. Hydrogen, methane, or propane, included in the gaseous product of pyrolysis reaction, is added in the ambient air. The fuel concentration is kept below the lean flammability limit to observe the partially premixing effect. Both experimental and numerical studies have been conducted. Results show that, in partially premixed atmospheres, both blue flame and luminous flame regions are enlarged, and the flame spread rate is increased. Based on the flame index, a so-called triple flame is observed. The heat release rate ahead of the original diffusion flame is increased by adding the fuel, and its profile is moved upstream. Here, we focus on the heat input by adding the fuel in the opposed air, which could be a direct factor to intensify the combustion reaction. The dependence of the flame spread rate on the heat input is almost the same for methane and propane/air mixtures, but larger effect is observed for hydrogen/air mixture. Since the deficient reactant in lean mixture is fuel, the larger effect of hydrogen could be explained based on the Lewis number consideration. That is, the combustion is surely intensified for all cases, but this effect is larger for lean hydrogen/air mixture (Le < 1), because more fuel diffuses toward the lean premixed flame ahead of the original diffusion flame. Resultantly, the pyrolysis reaction is promoted to support the higher flame spread rate.