Efficient dynamic kinetic resolution of racemic secondary alcohols by a chemoenzymatic system using bifunctional iridium complexes with C-N chelate amido ligands

The combined catalyst system of bifunctional amidoiridium complexes derived from benzylic amines with CALB was found to provide a range of chiral acetates from racemic secondary alcohols in excellent yields with nearly perfect enantioselectivities via dynamic kinetic resolution.     

FMO‐MD Simulations on the Hydration of Formaldehyde in Water Solution with Constraint Dynamics

Full‐quantum mechanical fragment molecular orbital‐based molecular dynamics (FMO‐MD) simulations were applied to the hydration reaction of formaldehyde in water solution under neutral conditions. Two mechanisms, a concerted and a stepwise one, were considered with respect to the nucleophilic addition and the proton transfer. Preliminary molecular orbital calculations by means of polarized continuum model reaction field predicted that the hydration prefers a concerted mechanism. Because the calculated activation barriers were too high for free FMO‐MD simulations to give reactive trajectories spontaneously, a More O’Ferrall–Jencks‐type diagram was constructed from the statistical analysis of the FMO‐MD simulations with constraint dynamics. The diagram showed that the hydration proceeds through a zwitterionic‐like (ZW‐like) structure. The free energy changes along the reaction coordinate calculated by means of the blue moon ensemble for the hydration and the amination of formaldehyde indicated that the hydration proceeds through a concerted process through the ZW‐like structure, whereas the amination goes through a stepwise mechanism with a ZW intermediate. In inspection of the FMO‐MD trajectories, water‐mediated cyclic proton transfers were observed in both reactions on the way from the ZW‐like structure to the product. These proton transfers also have an asynchronous character, in which deprotonation from the nucleophilic oxygen atom (or nitrogen atom for amination) precedes the protonation of the carbonyl oxygen atom. The results showed the strong advantage of the FMO‐MD simulations to obtain detailed information at a molecular level for solution reactions.     

Preparation, structure, and properties of tetranuclear vanadium(III) and (IV) complexes bridged by diphenyl phosphate or phosphate

Three novel tetranuclear vanadium(III) or (IV) complexes bridged by diphenyl phosphate or phosphate were prepared and their structures characterized by X-ray crystallography. The novel complexes are [{V(III)(2)(μ-hpnbpda)}(2){μ-(C(6)H(5)O)(2)PO(2)}(2)(μ-O)(2)]·6CH(3)OH (1), [{V(III)(2)(μ-tphpn)(μ-η(3)-HPO(4))}(2)(μ-η(4)-PO(4))](ClO(4))(3)·4.5H(2)O (2), and [{(V(IV)O)(2)(μ-tphpn)}(2)(μ-η(4)-PO(4))](ClO(4))(3)·H(2)O (3), where hpnbpda and tphpn are alkoxo-bridging dinucleating ligands. H(3)hpnbpda represents 2-hydroxypropane-1,3-diamino-N,N'-bis(2-pyridylmethyl)-N,N'-diacetic acid, and Htphpn represents N,N,N',N'-tetrakis(2-pyridylmethyl)-2-hydroxy-1,3-propanediamine. A dinuclear vanadium(IV) complex without a phosphate bridge, [(VO)(2)(μ-tphpn)(H(2)O)(2)](ClO(4))(3)·2H(2)O (4), was also prepared and structurally characterized for comparison. The vanadium(III) center in 1 adopts a hexacoordinate structure while that in 2 adopts a heptacoordinate structure. In 1, the two dinuclear vanadium(III) units bridged by the alkoxo group of hpnbpda are further linked by two diphenylphosphato and two oxo groups, resulting in a dimer-of-dimers. In 2, the two vanadium(III) units bridged by tphpn are further bridged by three phosphate ions with two different coordination modes. Complex 2 is oxidized in aerobic solution to yield complex 3, in which two of the three phosphate groups in 2 are substituted by oxo groups.     

Preparation of (Z)-1-fluoro-1-alkenyl carboxylates,carbonates and carbamates through chromium mediated transformation of dibromofluoromethylcarbinyl esters and the reactivity as double acyl group donors

CrCl₂/Mn-mediated transformation of various dibromofluoromethylcarbinyl esters including carboxylates, carbonates and carbamates provided 1-fluoro-1-alkenyl esters via [2,3]-sigmatropic rearrangement of ester group. Reaction proceeded by using CrCl₂/Mn system under mild conditions (in THF at room temperature) to give 1-fluoro-1-alkenyl esters in good yield with an excellent Z selective manner. 1-Fluoro-1-alkenyl ester thus obtained acts as a double acyl donor in the reaction with necleophiles such as amine, thiol, alcohol as well as bifunctional necleophiles such as ethylene diamine derivative.     

Altered posttranslational modification on U1 small nuclear ribonucleoprotein 68k in systemic autoimmune diseases detected by 2D Western blot

Anti-ribonucleoprotein (anti-RNP) antibodies are one of the representative autoantibodies detectable in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Generally, posttranslational modifications (PTMs) on autoantigens are proposed to be involved in the production of autoantibodies. In this study, we tried to detect the alteration in PTMs on a U1 small nuclear RNP 68k subunit (U1-68k), a major antigen of anti-RNP antibodies. Peripheral blood mononuclear cells (PBMCs) were obtained from patients with MCTD, SLE, and rheumatoid arthritis (RA), and from healthy donors. U1-68ks in the PBMCs were detected by 2D Western blot (WB), where extracted nuclear proteins were separated by 2DE, followed by the detection of U1-68k using WB. More than 20 PTM isoforms were detected with different molecular weights of 65.0 , 66.5, and 68.0kDa, and different pIs between 6.0 and 8.5. Importantly, the relative intensity of the spot with 66.5 kDa and pI 7.5 was significantly increased in the MCTD and SLE groups compared to the RA and healthy groups. Further, this U1-68k isoform, in particular, in its RS domain, was found to have significantly decreased phosphorylation compared to the other isoforms. The PTM alternation may be one of the steps to generate the anti-RNP antibodies.     

A modified repulsive bridge correction to accurate evaluation of solvation free energy in integral equation theory for molecular liquids

Integral equation theory for molecular liquids is one of the powerful frameworks to evaluate solvation free energy (SFE). Different from molecular simulation methods, the theory computes SFE in an analytical manner. In particular, the correction method proposed by Kovalenko and Hirata [Chem. Phys. Lett. 290, 237 (1998); and J. Chem. Phys. 113, 2793 (2000)] is quite efficient in the accurate evaluation of SFE. However, the application has been limited to aqueous solution systems. In the present study, an improved method is proposed that is applicable to a wide range of solution systems. The SFE of a variety of solute molecules in chloroform and benzene solvents is evaluated. A key is the adequate treatment of excluded volume in SFE calculation. By utilizing the information of chemical bonds in the solvent molecule, the accurate computation of SFE is achieved.     

Influence of peak inspiratory flow rates and pressure drops on inhalation performance of dry powder inhalers

The aim of this study was to reveal the relationship between human inspiratory flow patterns and the concomitant drops in pressure in different inhalation devices, and the influence of the devices on inhalation performance. As a model formulation for inhalers, a physically mixed dry powder composed of salbutamol sulfate and coarse lactose monohydrate was selected. The drops in pressure at 28.3?L/min of three inhalation devices, Single-type, Dual-type, and Reverse-type, was 1.0, 5.1, and 8.7?kPa, respectively. Measurements of human inspiratory patterns revealed that although the least resistant device (Single) had large inter- and intra-individual variation of peak flow rate (PFR), the coefficients of variation of PFR of the three devices were almost the same. In tests with a human inspiratory flow simulator in vitro, inhalation performance was higher, but the variation in inhalation performance in the range of human flow patterns was wider, for the more resistant device. To minimize the intra- and inter-individual variation in inhalation performance for the model formulation in this study, a formulation design that allows active pharmaceutical ingredient to detach from the carrier with a lower inhalation flow rate is needed.     

Nuclear Moment Studies with Polarized Radioactive Nuclear Beams

Magnetic dipole and electric quadrupole moments of nuclei in the light-mass neutron-rich region have been studied by taking advantage of spin-polarized radioactive nuclear beams that have been obtained from the projectile fragmentation reaction. Analyses of the results reveal a few interesting phenomena characteristic of nuclear structures in this region. In particular, we report in some detail the latest result on the magnetic moment of the ¹⁷C ground state. The distinctly small value of the g-factor obtained, |g(¹⁷C)|=0.5054±0.0025, clearly excludes a I ^π=1/2⁺ candidate for the spin-parity assignment of this marginally bound nucleus, providing a reasonable account of the non-halo nature reported in recent breakup reaction experiments. Finally, future plans at the upcoming radioactive beam facility presently under construction at RIKEN are briefly mentioned. This revised version was published online in September 2006 with corrections to the Cover Date.     

Precise Quadrupole Moment of the Doubly Closed Shell Plus One Proton Nucleus 41Sc

In order to precisely determine the |eqQ(⁴¹Sc)/h| of ⁴¹Sc(I ^π=7/2⁻, T _1/2=0.596 s) implanted in a TiO₂ single crystal the electric field gradient tensor and anisotropic chemical shift were determined by detecting the Fourier Transformed Pulse-NMR of ⁴⁵Sc(I ^π=7/2⁻, stable) in the crystal at a high field of 7.0 T and 9.4 T. Combining the new |eqQ(⁴¹Sc)/h| value with the Q(⁴⁵Sc)=−(23.6±0.2) fm², also renewed by using the known atomic hyperfine interaction constants and Sternheimer polarization effect, the |Q(⁴¹Sc;I ^π=7/2⁻,T _1/2=0.596 s)|=(15.6±0.3) fm² has been precisely determined. The value is compared with the theoretical Q(⁴¹Sc) given by a shell model code. This revised version was published online in September 2006 with corrections to the Cover Date.