Mono- and dihydroxylated metabolites of thalidomide: synthesis and TNF-alpha production-inhibitory activity

Mono- and dihydroxylated metabolites of thalidomide were efficiently prepared and characterized, and their inhibitory activity on tumor necrosis factor (TNF)-alpha production in the human monocytic leukemia cell line THP-1 was evaluated. 5,N-Dihydroxythalidomide was a much more potent TNF-alpha production inhibitor than thalidomide.     

Indoline derivatives I: synthesis and factor Xa (FXa) inhibitory activities

A series of bisamidine derivatives each having a ring structure in the center of the molecule was synthesized and their Factor Xa (FXa) inhibitory activities were evaluated. Among them, some indoline derivatives showed potent inhibitory activities in vitro. In particular, (R)-18a having an (R)-configuration at the 2-position of the indoline ring exhibited the most potent FXa inhibitory activity in vitro, more potent than DX-9065a. Furthermore, (R)-18a exhibited more potent anticoagulant activity than DX-9065a. We also succeeded in obtaining an X-ray crystal structure of FXa bound with (R)-18a.     

Theory of photoinduced heterogeneous electron transfer

We consider electron injection into the conduction band of a semiconductor, from an electronically excited state of a dye molecule, adsorbed on its surface. For arbitrary width of the conduction band, the survival probability of the excited state can be calculated using a Green's-function approach. We show that the existence of a split-off state can play an important role in the total injection probability. In the wide band limit, the survival probability decays exponentially, but for finite band widths it does not. We further investigate the effect of vibrations on the process. A Green's operator technique may be used to solve this too exactly. We show that the problem may be reduced to a non-Hermitian eigenvalue problem for the vibrational states alone. Exact results can be obtained for arbitrary bandwidth and for a few vibrational degrees of freedom. In the wide band limit, the dynamics is particularly simple and we find that (1) the survival probability of the excited state is unchanged by the inclusion of vibrational motion, but (2) each vibrational state now has a finite lifetime. Numerical results are presented for the effects of reorganization energy, energy of the injecting level, and the variation of the matrix element for the electron injection, on the survival probability of the electron in the excited state. As an illustration of the approach, we also present results of numerical calculation of the absorption spectrum of perylene adsorbed on TiO(2) and compare it with experimental results.     

H/D isotope effect on porphine and porphycene molecules with multicomponent hybrid density functional theory

To analyze the H/D isotope effect on porphine and porphycene molecules including the protonic/deuteronic quantum nature and electron correlation efficiently, the authors have developed the new scheme of the multicomponent hybrid density functional theory [MC_(HF+DFT)]. The optimized geometries of porphine, porphycene, and these deuterated isotopomers by our MC_(HF+DFT) method are in good agreement with the experimental "high-symmetric" structures, contrary to the "low-symmetric" geometries optimized by pure multicomponent Hartree-Fock method. The optimized geometries for HD-porphine and HD-porphycene molecules, in which an inner hydrogen is replaced to a deuterium, are found to be low symmetric. Such drastic geometrical change induces the electronic polarization, and gives rise to the slight dipole moment values in these HD species. Their results clearly indicate that the difference of the nuclear quantum nature between inner proton and inner deuteron directly influences the molecular geometry and electronic structure.     

A method for the low-level (ng g(-1)) determination of perfluorooctanoate in paper and textile by liquid chromatography with tandem mass spectrometry

The determination of perfluorooctanoate (PFO) in articles of commerce has become increasingly important to understand if treated products are a possible source of PFO. An LC-MS/MS method for the determination of PFO in paper and textile using a dual labeled 13C-PFOA internal standard was successfully developed and validated. Residues of PFO were determined using an isocratic, reversed-phase high-performance liquid chromatography (HPLC) method with an ammonium acetate/methanol buffer. Ions monitored were 413 (parent) and 369 (daughter) for PFO and 415 (parent) and 370 (daughter) for dual labeled 13C-PFOA internal standard. As a precaution against ubiquitous PFO that occasionally occurs in mobile phase or instrument components, two Hypercarb cartridges (4 mm) were placed before the HPLC injector. Any PFO that was captured by the cartridges was removed before each injection by flushing the system with 100% methanol prior to equilibration with the isocratic mobile phase. Overall recovery and standard deviation over a 3 day validation regimen for samples (n=54-55) fortified with PFOA at 5, 50, and 200 ng g(-1) were 114+/-4.9% for textile and 110+/-7.6% for paper. The results also established a limit of detection (LOD) of 1 ng g(-1) in textile and 2 ng g(-1) in paper based upon S/N of the 5.0 ng g(-1) fortification versus the untreated paper and textile.     

Redox properties of the ferricyanide ion on electrodes coated with layer-by-layer thin films composed of polysaccharide and poly(allylamine)

Polyelectrolyte multilayer thin films were prepared by an alternate deposition of poly(allylamine hydrochloride) (PAH) and anionic polysaccharides {carboxymethylcellulose (CMC) and alginic acid (AGA)} on the surface of a gold (Au) disk electrode, and the binding of ferricyanide [Fe(CN)(6)](3)(-) and hexaammine ruthenium ions [Ru(NH(3))(6)](3+) to the films was evaluated. Poly(acrylic acid) (PAA) was also employed as a reference polyanion bearing carboxylate side chains. A quartz-crystal microbalance study showed that PAH-CMC and PAH-AGA multilayer films grow exponentially as the number of depositions increases. The thicknesses of five bilayers of (PAH-CMC)(5) and (PAH-AGA)(5) films were estimated to be 150 +/- 20 and 90 +/- 15 nm, respectively, in the dry state. The PAH/polysaccharide multilayer film-coated Au electrodes exhibited a redox response to the [Fe(CN)(6)](3)(-) ion dissolved in solution, irrespective of the sign of the surface charge of the film, suggesting the high permeability of the films to the [Fe(CN)(6)](3)(-) ion. In contrast, the PAH-PAA film-coated Au electrodes exhibited a redox response only when the outermost surface of the film was covered with a positively charged PAH layer. However, the permeation of the [Ru(NH(3))(6)](3+) cation was severely suppressed for all of the multilayer films. It was possible to confine the [Fe(CN)(6)](3)(-) ion in the films by immersing the film-coated electrodes in a 1 mM [Fe(CN)(6)](3)(-) solution for 15 min. Thus, the [Fe(CN)(6)](3)(-)-confined electrodes exhibited a cyclic voltammetric response in the [Fe(CN)(6)](3)(-) ion-free buffer solution. The loading of the [Fe(CN)(6)](3)(-) ion in the films was higher when the surface charge of the film was positive and increased with increasing film thickness. It was also found that the [Fe(CN)(6)](3)(-) ion confined in the films serves as an electrocatalyst that oxidizes ascorbic acid in solution.     

Properties and reactivity of xanthyl radical in the excited state

The properties and reactivity of the 9-xanthyl radical (X(*)) in the doublet excited state (X(*)(D(1))) were investigated using nanosecond-picosecond two-color two-laser flash photolysis. The absorption and fluorescence spectra of X(*)(D(1)) were observed for the first time. The reactivity of X(*)(D(1)) toward a series of halogen donors and electron acceptors in acetonitrile and 1,2-dichloroethane (DCE) was investigated. It is confirmed that X(*)(D(1)) has a halogen abstraction ability from a series of halogen donors. On the basis of the solvent effect on the quenching rate constants of X(*)(D(1)), an electron transfer from X(*)(D(1)) to CCl(4) was indicated.     

Solvent effect on the deactivation processes of benzophenone ketyl radicals in the excited state

The solvent effects on ketyl radicals of benzophenone derivatives (BPD) in the excited state (BPDH*(D1)) were investigated. Absorption and fluorescence spectra of BPDH*(D1) in various solvents were measured using nanosecond-picosecond two-color two-laser flash photolysis. The fluorescence peaks from BPDH*(D1) showed a shift due to the dipole-dipole interaction with the solvent molecules. The dipole moments (mu(e)) of BPDH*(D1) were estimated to be 7-10 D, indicating that BPDH*(D1) are highly polarized. It was revealed that the fluorescence lifetime (tau(f)) depends on mu(e) in acetonitrile because the stabilization by solvent molecules affects the tau(f) value in polar solvents, predominantly. On the contrary, the conformation of BPDH*(D1) plays an important role in cyclohexane because the efficiency of the unimolecular reaction from BPDH*(D1) depends on the conformation. The substituent effect on the electron transfer from BPDH*(D1) to their parent molecules was also discussed.     

"Beta-cis-SAr effect" on decarbonylation from alpha,beta-unsaturated acyl and aroyl complexes

Lone pair of heteroatom located at the beta-cis position in alpha,beta-unsaturated acyl and aroyl group 10 metal complexes dramatically facilitated the stoichiometric and catalytic decarbonylation reactions.     

Self-assembled meso-helicates of linear trinuclear nickel(II)-radical complexes with triple pyrazolate bridges

Complexation of 3-nitronyl-nitroxide-substituted pyrazolate (pzNN) and 3-imino-nitroxide-substituted pyrazolate (pzIN) with nickel(II) gave [Ni3(pzNN)6] and [Ni3(pzIN)6], respectively. They were practically isomorphous and characterized as a linear trinuclear structure with neighboring nickel ions triply bridged by pyrazolate moieties. The space groups were P2(1)/n but the molecules have a pseudo three-fold axis. We found polymorphs in the crystals of [Ni3(pzIN)6] depending on the solvate molecules; another space group was a cubic Pa3[combining macron]. The opposite chirality around the inversion center at the central nickel(II) ion leads to a meso-helical symmetry in the whole molecule. The radical oxygen atoms participate in the 6-membered chelation at the terminal nickel(II) ions. Antiferromagnetic couplings were observed in both complexes, which are ascribable to interactions between the nickel and radical spins and between the nickel spins across the pyrazolate bridges.