Tetsuji Itoh

Persistent triplet carbenes.

ion and the formation of the dimer was decreased to 26%. The difference in the product distribution can be interpreted as reflecting the difference in the extent of steric crowdedness around the carbenic center between these two carbenes. Thus, in 100b, each of four chlorine groups around the carbene center is buttressed by one of the four meta Table 47. Kinetic Data of Di[1,2,3,4,5,6,7,8-octahydro-1,4:5,8-di(ethano)anthryl]carbenesa,152 a Measured in benzene at room temperature.

Encapsulation of hemoglobin in mesoporous silica (FSM)- : Enhanced thermal stability and resistance to denaturants

Hemoblogin (Hb), which is a typical oligomeric protein, was introduced into the pores of mesoporous silica (FSM: folded‐sheet mesoporous material) that had a diameter of 7.5 nm. Soret CD spectra of Hb–FSM‐7.5 conjugates showed a peak that was identical to that of free Hb. This suggests that Hb retained its highly ordered structure in the mesoporous silica. In addition, the UV‐visible absorption spectrum showed that Hb had an increased resistance to heat denaturation in the silica. Even after heat treatment at 85 °C, Hb–FSM‐7.5 retained its ligand‐binding activity. The stability of Hb–FSM‐7.5 was examined further by measuring its peroxidase‐like activity. Encapsulation of Hb resulted in the retention of activity in the presence of high NaCl or Gdn‐HCl levels. This suggests that encapsulation prevented dissociation and denaturing. Thus, it seems that the mesopores created a favorable environment for the oligomeric protein to perform its function, even under harsh conditions.

Amperometric determination of choline with enzyme immobilized in a hybrid mesoporous membrane.

Choline sensor is successfully prepared by using immobilized enzyme, i.e., choline oxidase (ChOx) within a hybrid mesoporous membrane with 12 nm pore diameter (F127M). The measurement was based on the detection of hydrogen peroxide, which is the co-product of the enzymatic choline oxidation. The determination range and the response time are 5.0-800 microM and approximately 2 min, respectively. The sensor is very stable compared to the native enzyme sensor and 85% of the initial response was maintained even after storage for 80 days. These results indicate that ChOx is successfully immobilized and well stabilized, and at the same time, enzyme reaction proceeds efficiently. Such ability of hybrid mesoporous membrane F127M suggests great promise for effective immobilization of enzyme useful for electrochemical biosensors.

Asymmetric synthesis of telcagepant, a CGRP receptor antagonist for the treatment of migraine.

A highly efficient, asymmetric synthesis of telcagepant (1), a CGRP receptor antagonist for the treatment of migraine, is described. This synthesis features the first application of iminium organocatalysis on an industrial scale. The key to the success of this organocatalytic transformation was the identification of a dual acid cocatalyst system, which allowed striking a balance of the reaction efficiency and product stability effectively. As such, via an iminium species, the necessnary C-6 stereogenicity was practically established in one operation in >95% ee. Furthermore, we enlisted an unprecedented Doebner-Knoevenagel coupling, which was also via an iminium species, to efficiently construct the C3-C4 bond with desired functionality. In order to prepare telcagepant (1) in high quality, a practical new protocol was discovered to suppress the formation of desfluoro impurities formed under hydrogenation conditions to <0.2%. An efficient lactamization facilitated by t-BuCOCl followed by a dynamic epimerization-crystallization resulted in the isolation of caprolactam acetamide with the desired C3 (R) and C6 (S) configuration cleanly. Isolating only three intermediates, the overall yield of this cost-effective synthesis was up to 27%. This environmentally responsible synthesis contains all of the elements required for a manufacturing process and prepares telcagepant (1) with the high quality required for pharmaceutical use.

Synthesis of new microporous layered organic–inorganic hybrid nanocomposites by alkoxysilylation of a crystalline layered silicate, ilerite

We have developed microporous organic–inorganic hybrid nanocomposites by alkoxysilylation of 4,4′-biphenyl-bridged alkoxysilane compounds, which contain triethoxysilyl, methyldiethoxysilyl, and dimethylethoxysilyl groups at each end of the 4,4′-biphenylene unit ((CH3)n(C2H5O)3−n-Si-C12H8-Si-(OC2H5)3−n(CH3)n, n = 0, 1, or 2, abbreviated as BESB(0), BESB(2), or BESB(4), respectively, where the number in parentheses indicates the number of methyl groups in these molecules), in the interlayer of a crystalline layered silicate, ilerite. XRD, 29Si solid-state NMR and fluorescence spectroscopy revealed the immobilization and bridging formation of the BESB molecules between the silicate layers by condensation, not only with H-ilerite, but also with the BESB molecules. The interlayer structures exhibited different molecular arrangements. BESB(0) and BESB(4) molecules are present as a monolayer arrangement in which BESB(0) molecules form the oligomeric species caused by close stacking like a dimer. BESB(2) molecules form mainly bilayer-like aggregates in the interlayer. The structural differences are caused by the different reactivities of the BESB molecules, which control their polymerization in the interlayer. The resultant BESB(0)- and BESB(2)-ilerite had high microporosity with BET surface areas (508 and 578 m2 g−1 for BESB(0)- and BESB(2)-ilerite, respectively). The micropores showed higher toluene adsorptivity than several other porous silica materials due to the successful surface modification. Consequently, this approach provides a new method for constructing novel microporous nanocomposites, the key to improved selectivity and activity in separation and catalytic applications.

Mesoporous silica hybrid membranes for precise size-exclusive separation of silver nanoparticles

One-dimensional (1D) nanomaterials have unique applications due to their inherent physical properties. In this study, hexagonally ordered mesoporous silica hybrid anodic alumina membranes (AAM) were synthesized using template-guided synthesis with a number of nonionic n-alkyl-oligo(ethylene oxide), Brij-type (C(x)EO(y)), which are surfactants that have different molecular sizes and characteristics. The hexagonal mesoporous silicas are vertically aligned in the AAM channels with a predominantly columnar orientation. The hollow mesostructured silicas had tunable pore diameters varying from 3.7 to 5.1 nm. In this synthesis protocol, the surfactant molecular natures (corona/core features) are important for the controlled generation of ordered structures throughout AAM channels. The development of ultrafiltration membranes composed of silica mesostructures could be used effectively in separating silver nanoparticles (Ag NPs) in both aqueous and organic solution phases. This would be relevant to the production of well-defined Ag NPs with unique properties. To create a size-exclusive separation system of Ag NPs, we grafted hydrophobic trimethylsilyl (TMS) groups onto the inner pores of the mesoporous silica hybrid AAM. The immobilization of the TMS groups allowed the columnar mesoporous silica inside AAM to retain this inner pore order without distortion during the separation of solution-phase Ag NPs in organic solvents that may cause tortuous-pore membranes. Mesoporous TMS-silicas inside 1D AAM channels were applicable as a size-exclusive separation system to isolate organic solution-phase Ag NPs of uniform morphology and size.

Enhancement in thermal stability and resistance to denaturants of lipase encapsulated in mesoporous silica with alkyltrimethylammonium (CTAB)

We assembled a highly durable conjugate with both a high-density accumulation and a regular array of lipase, by encapsulating it in mesoporous silica (FSM) with alkyltrimethylammonium (CTAB) chains on the surface. The activity for hydrolyzing esters of the lipase immobilized in mesoporous silica was linearly related to the concentration of lipase, whereas that of non-immobilized lipase showed saturation due to self-aggregation at a high concentration. The lipase conjugate also had increased resistance to heating when stayed in the silica coupling with CTAB. In addition, encapsulating the enzyme with FSM coupled CTAB caused the lipase to remain stable even in the presence of urea and trypsin, suggesting that the encapsulation prevented dissociation and denaturing. This conjugate had much higher activity and much higher stability for hydrolyzing esters when compared to the native lipase. These results show that FSM provides suitable support for the immobilization and dispersion of proteins in mesopores with disintegration of the aggregates.

Acid-base equilibria inside amine-functionalized mesoporous silica.

Acid-base equilibria and effective proton concentration inside a silica mesopore modified with a trimethyl ammonium (TMAP) layer were studied by steady-state fluorescence experiments. The mesoporous silica with a dense TMAP layer (1.4 molecules/nm(2)) was prepared by a post grafting of N-trimethoxysilylpropyl-N,N,N-trimethylammonium at surfactant-templated mesoporous silica (diameter of silica framework =3.1 nm). The resulting TMAP-modified mesoporous silica strongly adsorbed of anionic fluorescence indicator dyes (8-hydroxypyrene-1,3,6-trisulfonate (pyranine), 8-aminopyrene-1,3,6-trisulfonate (APTS), 5,10,15,20-tetraphenyl-21H,23H-porphinetetrasulfonic acid disulfuric acid (TPPS), 2-naphthol-3,6-disulfonate (2NT)) and fluorescence excitation spectra of these dyes within TMAP-modified mesoporous silica were measured by varying the solution pH. The fluorescence experiments revealed that the acid-base equilibrium reactions of all pH indicator dyes within the TMAP-modified silica mesopore were quite different from those in bulk water. From the analysis of the acid-base equilibrium of pyranine, the following relationships between solution pH (pH(bulk)) and the effective proton concentration inside the pore (pH(pore)) were obtained: (1) shift of pH(pore) was 1.8 (ΔpH(pore)=1.8) for the pH(bulk) change from 2.1 to 9.1 (ΔpH(bulk)=7.0); (2) pH(pore) was not simply proportional to pH(bulk); (3) the inside of the TMAP-modified silica mesopore was suggested to be in a weak acidic or neutral condition when pH(bulk) was changed from 2.0 to 9.1. Since these relationships between pH(bulk) and pH(pore) could explain the acid-base equilibria of other pH indicator dyes (APTS, TPPS, 2NT), these relationships were inferred to describe the effective proton concentration inside the TMAP-modified silica mesopore.

A Triphenylamine Derivative with Three p‐(N‐tert‐Butyl‐N‐oxylamino)phenyl Radical Units and Yet a Doublet Ground State

A superexchange interaction through the lone pair of electrons on the central nitrogen atom in 1 is invoked to explain the existence of a doublet ground state; two spins on the aminoxyl radical centers couple antiferromagnetically, and one spin remains intact. This proposal is supported by EPR spectroscopic and magnetic measurements.

Solvation dynamics of coumarin 153 in alcohols confined in silica nanochannels.

Solvation dynamics in alcohols confined in silica nanochannels was examined by time-resolved fluorescence spectroscopy using coumarin 153 (C153) as a fluorescent probe. Surfactant-templated mesoporous silica was fabricated inside the pores of an anodic alumina membrane. The surfactant was removed by calcination to give mesoporous silica (Cal-NAM) containing one-dimensional (1D) silica nanochannels (diameter, 3.1 nm) whose inner surface was covered with silanol groups. By treating Cal-NAM with trimethylchlorosilane, trimethylsilyl (TMS) groups were formed on the inner surface of the silica nanochannels (TMS-NAM). Fluorescence dynamic Stokes shifts of C153 were measured in alcohols (ethanol, butanol, hexanol, and decanol) confined in the silica nanochannels of Cal- and TMS-NAMs, and the time-dependent fluorescence decay profiles could be best fitted by a biexponential function. The estimated solvent relaxation times were much larger than those observed in bulk alcohols for both Cal- and TMS-NAMs when ethanol or butanol was used as a solvent, indicating that the mobility of these alcohol molecules was restricted within the silica nanochannels. However, hexanol or decanol in Cal- and TMS-NAMs did not cause a remarkable increase in the solvent relaxation time in contrast to ethanol or butanol. Therefore, it was concluded that a relatively rigid assembly of alcohols (an alcohol chain) was formed within the silica nanochannels by hydrogen bonding interaction and van der Waals force between the surface functional groups of the silica nanochannels and alcohol molecules and by the successive interaction between alcohol molecules when alcohol with a short alkyl chain (ethanol or butanol) was used as a solvent.