Kinetic study on the mechanism of inhibition of trypsin and trypsin-like enzymes by p-guanidinobenzoate ester

It was found that [4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate]methanesulfonate (E-3123) inhibits trypsin, thrombin and kallikrein, and its inhibitory activity is most potent toward trypsin. The interactions of these enzymes with E-3123 were studied mainly by using stopped-flow spectrophotometry. E-3123 behaved as a quasi-substrate of the enzymes and the inhibitory property was due to the efficient production of the stable acyl-enzyme. The acylation process with trypsin was exceedingly effective, and the resulting acyl-enzyme was the most stable among the three enzymes tested. This observation affords a rational basis for explaining the action of E-3123, which is a transient inhibitor most active toward trypsin.     

Impact of the macrocyclic structure and dynamic solvent effect on the reactivity of a localised singlet diradicaloid with π-single bonding character

Localised singlet diradicals are key intermediates in bond homolysis processes. Generally, these highly reactive species undergo radical–radical coupling reaction immediately after their generation. Therefore, their short-lived character hampers experimental investigations of their nature. In this study, we implemented the new concept of “stretch effect” to access a kinetically stabilised singlet diradicaloid. To this end, a macrocyclic structure was computationally designed to enable the experimental examination of a singlet diradicaloid with π-single bonding character. The kinetically stabilised diradicaloid exhibited a low carbon–carbon coupling reaction rate of 6.4 × 10³ s⁻¹ (155.9 μs), approximately 11 and 1000 times slower than those of the first generation of macrocyclic system (7.0 × 10⁴ s⁻¹, 14.2 μs) and the parent system lacking the macrocycle (5 × 10⁶ s⁻¹, 200 ns) at 293 K in benzene, respectively. In addition, a significant dynamic solvent effect was observed for the first time in intramolecular radical–radical coupling reactions in viscous solvents such as glycerin triacetate. This theoretical and experimental study demonstrates that the stretch effect and solvent viscosity play important roles in retarding the σ-bond formation process, thus enabling a thorough examination of the nature of the singlet diradicaloid and paving the way toward a deeper understanding of reactive intermediates.

An extremely long-lived localised singlet diradical with π-single bonding character is found in a macrocyclic structure that retards the radical–radical coupling reaction by the “stretch and solvent-dynamic effects”.     

DFT calculations on the effects of para substituents on the energy differences between singlet and triplet states of 2,2-difluoro-1,3-diphenylcyclopentane-1,3-diyls

UB3LYP/6-31g* calculations have been performed on a series of para-substituted 2,2-difluoro-1,3-diphenylcyclopentane-1,3-diyls (4). The singlet is computed to be the ground state for each of the diradicals, regardless of the nature of the para substituents, which range from strongly pi-electron-donating (amino) to strongly pi-electron-withdrawing (nitro). In the symmetrically para-disubstituted diradicals, the size of the singlet-triplet energy gap (Delta E(ST)) increases with the pi-electron-donating ability of the substituents, but in the unsymmetrically substituted diradicals, large values of Delta E(ST) are calculated even when one of the substituents is a pi electron acceptor. The origins of the competitive and cooperative substituent effects, predicted for diradical 4, are discussed in light of the calculated effects of the same substituents on the singlet and triplet states of diradical 6, which lacks the geminal fluorines at C-2 that are present in 4.     

Adsorption properties of gases on mesoporous chromium silicate

The properties of nitrogen, carbon dioxide, and nitrogen dioxide adsorption onto mesoporous chromium silicates were studied by measurements of both the adsorption isotherms and the IR spectra. The pore sizes of two types of chromium silicates, Cr-FSM-16 (Si/Cr=170 (Cr-FSM-16 [170]) and 390 (Cr-FSM-16 [390])), which contain different amount of Cr, were 2.75 nm. BET surface areas of Cr-FSM-16 were 590 m2/g and they were smaller than that onto FSM-16. The initial heat of adsorption of nitrogen onto Cr-FSM-16 was higher than that onto FSM-16. But the initial heat of adsorption of carbon dioxide onto Cr-FSM-16 was smaller than that onto FSM-16. These results indicated that Cr in Cr-FSM-16 decreased adsorption interaction with carbon dioxide. When nitrogen dioxide was adsorbed on FSM-16 and Cr-FSM-16 at 303 K under no light, an absorption band of nitrogen monoxide adsorbed was measured by IR spectroscopy. This decomposition of nitrogen dioxide by FSM-16 and Cr-FSM-16 was caused by SiOH and Cr, respectively.     

Epimerization of diastereomeric alpha-amino nitriles to single stereoisomers in the solid state

[reaction: see text] A diastereomeric mixture of the alpha-amino nitrile prepared by the Strecker reaction of benzaldehyde, (1S,2R)-1-aminoindan-2-ol, and cyanotrimethylsilane thermally epimerizes in the solid state to give a single diastereomer with an (S)-configuration at the alpha position to the nitrile moiety. This shows a sharp contrast to the reaction conducted in DMSO at room temperature, which gives a 1:1 mixture of (S)- and (R)-isomers. Several other alpha-amino nitriles also epimerize in the solid-state toward single diastereomers.     

Phase equilibrium in the system Ln-Mn-O: V. Ln=Yb and Dy at 1100°C

Phase equilibrium was established in the Yb-Mn-O and Dy-Mn-O systems at 1100°C by varying the oxygen partial pressure from −log (P_O2/atm)=0-13.00, allowing construction of phase diagrams at 1100°C for the systems Ln₂O₃-MnO-MnO₂. Under experimental conditions, Yb₂O₃, MnO, Mn₃O₄, and YbMnO₃ phases are found to be present in the Yb-Mn-O system, whereas Dy₂O₃, MnO, Mn₃O₄ DyMnO₃, and DyMn₂O₅ phases are present in the Dy-Mn-O system. Ln₂MnO₄, Mn₂O₃, and MnO₂ are not stable in either system. Small nonstoichiometric ranges are found in the LnMnO₃ phase, with the nonstoichiometry represented by the equations, N_O/N_YbMnO3=1.00×10⁻⁴(log P_O2)³+1.30×10⁻³(log P_O2)²+7.20×10⁻³(log P_O2)+5.00×10⁻⁵ and N_O/N_DyMnO3=1.00×10⁻⁴(log P_O2)³+1.80×10⁻³(log P_O2)²+9.30×10⁻³(log P_O2)+1.69×10⁻². Activities of the components in the solid solutions are calculated using these equations. LnMnO₃ may range Ln₂O₃-rich to Ln₂O₃-poor, while MnO is slightly nonstoichiometric to the oxygen-rich side. DyMn₂O₅ also seems to be nonstoichiometric. Lattice constants of LnMnO₃ under different oxygen partial pressures were determined, as well as lattice constants of DyMn₂O₅ quenched in air. The standard Gibbs energy changes of reactions appearing in the phase diagrams were calculated.     

Simultaneous manifestation of metallic conductivity and single-molecule magnetism in a layered molecule-based compound

Single-molecule magnets (SMMs) show superparamagnetic behaviour below blocking temperature at the molecular scale, so they exhibit large magnetic density compared to the conventional magnets. Combining SMMs and molecular conductors in one compound will bring about new physical phenomena, however, the synergetic effects between them still remain unexplored. Here we present a layered molecule-based compound, β′′-(BEDO-TTF)₄ [Co(pdms)₂]·3H₂O (BO4), (BEDO-TTF (BO) and H₂pdms are bis(ethylenedioxy)tetrathiafulvalene and 1,2-bis(methanesulfonamido)benzene, respectively), which was synthesized by using an electrochemical approach and studied by using crystal X-ray diffraction. This compound simultaneously exhibited metallic conductivity and SMM behaviour up to 11 K for the first time. The highest electrical conductivity was 400–650 S cm⁻¹ at 6.5 K, which is the highest among those reported so far for conducting SMM materials. Furthermore, antiferromagnetic ordering occurred below 6.5 K, along with a decrease in conductivity, and the angle-independent negative magnetoresistance suggested an effective electron correlation between the conducting BO and Co(pdms)₂ SMM layers (d–π interactions). The strong magnetic anisotropy and two-dimensional conducting plane play key roles in the low-temperature antiferromagnetic semiconducting state. BO4 is the first compound exhibiting antiferromagnetic ordering among SMMs mediated by π-electrons, demonstrating the synergetic effects between SMMs and molecular conductors.

A metallic single-molecule magnet was synthesised demonstrating simultaneous metallic conduction and excellent SMM properties at the same temperature range for the first time, with potential applications in molecule-based quantum spintronics.     

Efficient Generation and Synthetic Applications of Alkyl-Substituted Siloxycarbenes: Suppression of Norrish-Type Fragmentations of Alkanoylsilanes by Triplet Energy Transfer

Acylsilanes have been known to undergo isomerization to siloxycarbenes under photoirradiation and the thus generated carbenes can be utilized for various synthetic reactions. But this carbene formation is not necessarily efficient with some alkanoylsilanes because Norrish-type fragmentations compete, which limit the synthetic utility of alkanoylsilanes as carbene precursors. In this study, generation of siloxycarbenes from alkanoylsilanes by visible-light-induced energy transfer was examined by using an Ir complex, [Ir{dF(CF₃)ppy}₂(dtbpy)]PF₆, and was successfully applied to the C−C coupling reactions with boronic esters or aldehydes. This methodology efficiently suppressed undesired Norrish-type reactions and broadened synthetic utility of alkanoylsilanes.