Kiyonori Takegoshi

An oxyhydride of BaTiO3 exhibiting hydride exchange and electronic conductivity

In oxides, the substitution of non-oxide anions (F(-),S(2-),N(3-) and so on) for oxide introduces many properties, but the least commonly encountered substitution is where the hydride anion (H(-)) replaces oxygen to form an oxyhydride. Only a handful of oxyhydrides have been reported, mainly with electropositive main group elements or as layered cobalt oxides with unusually low oxidation states. Here, we present an oxyhydride of the perhaps most well-known perovskite, BaTiO(3), as an O(2-)/H(-) solid solution with hydride concentrations up to 20% of the anion sites. BaTiO(3-x)H(x) is electronically conducting, and stable in air and water at ambient conditions. Furthermore, the hydride species is exchangeable with hydrogen gas at 400 °C. Such an exchange implies diffusion of hydride, and interesting diffusion mechanisms specific to hydrogen may be at play. Moreover, such a labile anion in an oxide framework should be useful in further expanding the mixed-anion chemistry of the solid state.

Rotational resonance in the tilted rotating frame

Abstract We propose a new solid-state NMR technique under magic-angle spinning to recouple the dipolar interaction for a particular pair of homonuclear spins. In this method, a weak radio-frequency field is applied during the mixing time of the exchange NMR, and its frequency and intensity are chosen to realize rotational resonance for a particular pair of spins in the tilted rotating frame. The selective recoupling is demonstrated for the dipolar interaction between the CH and CH 3 carbons in triply 13 C-enriched l -alanine, whose chemical shift difference is too small to apply the conventional rotational resonance method.

Site-specific Inhibitory Mechanism for Amyloid β42 Aggregation by Catechol-type Flavonoids Targeting the Lys Residues

Background: The inhibitory mechanism of Aβ42 aggregation by flavonoid is fully unknown. Results: The oxidant enhanced the inhibitory activity of (+)-taxifolin against Aβ42 aggregation by forming Aβ42-taxifolin adducts between the Lys residues and oxidized (+)-taxifolin. Conclusion: The inhibitory activity of catechol-type flavonoids requires autoxidation to form an o-quinone to react with Lys. Significance: These may help design promising inhibitors against Aβ42 aggregation for Alzheimer disease therapy. The aggregation of the 42-residue amyloid β-protein (Aβ42) is involved in the pathogenesis of Alzheimer disease (AD). Numerous flavonoids exhibit inhibitory activity against Aβ42 aggregation, but their mechanism remains unclear in the molecular level. Here we propose the site-specific inhibitory mechanism of (+)-taxifolin, a catechol-type flavonoid, whose 3′,4′-dihydroxyl groups of the B-ring plays a critical role. Addition of sodium periodate, an oxidant, strengthened suppression of Aβ42 aggregation by (+)-taxifolin, whereas no inhibition was observed under anaerobic conditions, suggesting the inhibition to be associated with the oxidation to form o-quinone. Because formation of the Aβ42-taxifolin adduct was suggested by mass spectrometry, Aβ42 mutants substituted at Arg5, Lys16, and/or Lys28 with norleucine (Nle) were prepared to identify the residues involved in the conjugate formation. (+)-Taxifolin did not suppress the aggregation of Aβ42 mutants at Lys16 and/or Lys28 except for the mutant at Arg5. In addition, the aggregation of Aβ42 was inhibited by other catechol-type flavonoids, whereas that of K16Nle-Aβ42 was not. In contrast, some non-catechol-type flavonoids suppressed the aggregation of K16Nle-Aβ42 as well as Aβ42. Furthermore, interaction of (+)-taxifolin with the β-sheet region in Aβ42 was not observed using solid-state NMR unlike curcumin of the non-catechol-type. These results demonstrate that catechol-type flavonoids could specifically suppress Aβ42 aggregation by targeting Lys residues. Although the anti-AD activity of flavonoids has been ascribed to their antioxidative activity, the mechanism that the o-quinone reacts with Lys residues of Aβ42 might be more intrinsic. The Lys residues could be targets for Alzheimer disease therapy.

Identification of Physiological and Toxic Conformations in Aβ42 Aggregates

Aggregation of the 42‐residue amyloid β‐protein (Aβ42) plays a crucial role in the pathogenesis of Alzheimers disease (AD). Despite numerous structural studies on Aβ aggregates, the relationship between tertiary structure and toxicity remains unclear. Our proline scanning and solid‐state NMR studies suggested that aggregates both of wild‐type Aβ42 and of E22K‐Aβ42 (one of the mutants related to cerebral amyloid angiopathy) contain two conformers: a major one with a turn at positions 25 and 26, and a minor one with a turn at positions 22 and 23. To identify the toxic conformer, the derivative Aβ42‐lactam(22K–23E), in which the side chains at positions 22 and 23 were covalently linked, was synthesized as a minor conformer surrogate, along with Aβ42‐lactam(25K–26E) as a major conformer surrogate. The Aβ42‐lactam(22K–23E) showed stronger aggregation, neurotoxicity, radical generation, and oligomerization than wild‐type Aβ42, whereas in Aβ42‐lactam(25K–26E) were weak. The transition from the physiological conformation with a turn at positions 25 and 26 to the toxic conformation with a turn at positions 22 and 23 might be a key event in the pathogenesis of AD.

Solid-state NMR analysis of interaction sites of curcumin and 42-residue amyloid β-protein fibrils.

Aggregation of 42-residue amyloid β-protein (Aβ42) plays a pivotal role in the etiology of Alzheimers disease (AD). Curcumin, the yellow pigment in the rhizome of turmeric, attracts considerable attention as a food component potentially preventing the pathogenesis of AD. This is because curcumin not only inhibits the aggregation of Aβ42 but also binds to its aggregates (fibrils), resulting in disaggregation. However, the mechanism of interaction between curcumin and the Aβ42 fibrils remains unclear. In this study, we analyzed the binding mode of curcumin to the Aβ42 fibrils by solid-state NMR using dipolar-assisted rotational resonance (DARR). To improve the quality of 2D spectra, 2D DARR data were processed with the covariance NMR method, which enabled us to detect weak cross peaks between carbons of curcumin and those of the Aβ42 fibrils. The observed (13)C-(13)C cross peaks indicated that curcumin interacts with the 12th and 17-21st residues included in the β-sheet structure in the Aβ42 fibrils. Interestingly, aromatic carbons adjacent to the methoxy and/or hydroxy groups of curcumin showed clear cross peaks with the Aβ42 fibrils. This suggested that these functional groups of curcumin play an important role in its interaction with the Aβ42 fibrils.

Three-dimensional structure determination of a uniformly labeled molecule by frequency-selective dipolar recoupling under magic-angle spinning

The complete three-dimensional (3D) structure of a glycylisoleucine (Gly-Ile) molecule was determined by individually measuring six dihedral angles with a frequency-selective homonuclear dipolar recoupling method, R2TR (rotational resonance in the tilted rotating frame), using a powder sample of diluted uniformly 13,15-labeled Gly-Ile. Each dihedral angle was obtained by recoupling a dipolar interaction between three or four bonds distant spins concerned or observing a dipolar correlation 2D powder pattern. The 3D structure of a Gly-Ile molecule was also determined by X-ray crystallography, and a good agreement with the NMR result was obtained. The results demonstrate that the R2TR method in a uniformly labeled powder sample can provide the 3D structure without the need to prepare a lot of selectively labeled samples.

Modulatory resonance recoupling of heteronuclear dipolar interactions under magic angle spinning

Abstract A new solid-state NMR technique for recoupling heteronuclear dipolar interactions under magic angle spinning is proposed. In this method, the recoupling is achieved by interference between two non-commutable time-dependent Hamiltonians in the doubly rotating frame: one is the heteronuclear dipolar interaction modulated by MAS and the other is the rf interaction whose amplitude is modulated. When the two modulation frequencies are matched to each other, the cross term between the two interactions becomes time-independent. Since the recoupling condition does not include the intensity of the rf field, this recoupling method is insensitive to inhomogeneity of the rf field. This new recoupling method is demonstrated for 2- 13 C/ 15 N doubly labeled glycine.

Sensitive (13)C- (13)C correlation spectra of amyloid fibrils at very high spinning frequencies and magnetic fields.

Sensitive 2D solid-state 13C–13C correlation spectra of amyloid β fibrils have been recorded at very fast spinning frequencies and very high magnetic fields. It is demonstrated that PARIS-xy recoupling using moderate rf amplitudes can provide structural information by promoting efficient magnetization transfer even under such challenging experimental conditions. Furthermore, it has been shown both experimentally and by numerical simulations that the method is not very sensitive to dipolar truncation effects and can reveal direct transfer across distances of about 3.5–4Å.

Dynamic nuclear polarization by photoexcited-triplet electron spins in polycrystalline samples

Abstract It is shown that the large electron spin polarization created in the photoexcited triplet species can be transferred to the nuclear spins even in a polycrystalline sample by utilizing a partial area of the extremely broad ESR powder spectrum for cross polarization (CP). The proton polarization 3160 times as large as the thermal equilibrium value was obtained in 0.018 mol% pentacene-doped naphthalene at 100 K in a field of 0.319 T. The influence of the proton spin–lattice relaxation and the sample thickness on the attained polarization is discussed.

Structural analysis of polyacenic semiconductor (PAS) materials with 129Xenon NMR measurements

Abstract Structural analysis of the polyacenic semiconductor (PAS) material prepared by the pyrolysis of phenol-formaldehyde resin at relatively low temperature (680 °C) has been performed by applying 129Xe nuclear magnetic resonance (NMR) measurements. One can obtain information on the microporous structure of the PAS material through adsorption of Xe atoms, since a 129Xe nucleus is a very sensitive probe of its microscopic environment. All the introduced Xe atoms were adsorbed on the internal surface of the pure PAS sample, which indicated remarkably large surface area of the PAS material. The average pore size of the pure PAS sample has been determined to be 7.7 ± 1.6 A from the pressure dependence of the Xe NMR chemical shift. In connection with the application of the PAS material to the electrode of the Li rechargeable battery, changes in the Xe NMR spectrum brought about by extrinsic additives such as binder, electrolyte solvent, and the doped Li have been investigated. In particular, it has been found that the Li-doping entirely prevents Xe atoms from entering into the micropores of the PAS material, probably due to adsorption of the solvent molecules on the internal surface of the micropores.