Synthesis and evaluation of 2-Nonylaminopyridine derivatives as PPAR ligands

To find novel PPAR ligands, we prepared several 3-{3 or 4-[2-(nonylpyridin-2-ylamino)ethoxy]phenyl}propanoic acid derivatives which were designed based on the structure of our previous PPARgamma ligand 1. In PPAR binding affinity assays, compound 4, which had an ethoxy group at the C-2 position of the propanoic acid of 1, showed selective binding affinity for PPARgamma. Compound 3, with an ethyl group at the C-2 position, was found to be a PPARalpha/gamma dual ligand. Compound 6, the meta isomer of 1, has been shown to be a PPARalpha ligand. The introduction of methyl (7) and ethyl (8) groups to the C-2 position of the propanoic acid of 6 further improved PPARalpha-binding potency. In cell-based transactivation assay, compounds 3 and 4 showed dual-agonist activity toward PPARalpha and PPARgamma. Compound 6 was found to be a triple agonist and compound 8 proved to be a selective PPARalpha agonist. In the human hypodermic preadipocyte differentiation test, it was demonstrated that the maximal activity of compounds 3 and 4 was higher than that of rosiglitazone.     

Effects of Y (Ⅲ) Ions on the Fluorescence Properties of Ce(Ⅲ) Ion and the Organic Ligands in the Complex

The enhancement effects of Y ( Ⅲ) ions on the fluorescence of Ce ( Ⅲ) in Ce ( Ⅲ)-Y ( Ⅲ)-PMMA (polymethylmethacrylate ) or Ce ( Ⅲ)-Y ( Ⅲ)-PVC (polyvinyl chloride ) complex systems were observed. The influence of Y ( Ⅲ) ions on the emission spectra of PMMA ligands in PMMA-Y ( Ⅲ) and the fluorescent enhance- ment of Y( Ⅲ) on Ce( Ⅲ) emission in PMMA-Ce-Y by Y( Ⅲ) ion were studied. It was also of interest to note that when Y ( Ⅲ) ions were added into PMMA and into bpy(bipyridine ), respectively, the emission spectrum of PMMA ligands was split into fine structure bands by Y ( Ⅲ), and the fluorescence intensities of bpy ligands in bpy-Y ( Ⅲ) complexes were considerably increased.     

Response of protonic acid‐doped poly(o‐anisidine)/poly(vinyl alcohol) composites to relative humidity and role of dopant anions

Various protonated poly(o‐anisidine) (PoAN)/poly(vinyl alcohol) (PVA) composites were prepared with different types of acids: sulfuric (SA), p‐toluene sulfonic (TSA), camphor sulfonic (CSA), and p‐dodecylbenzene sulfonic (DBSA). In the visible spectrum of each composite in dimethyl sulfoxide, three absorption peaks were observed at 440, 620, and 860 nm. The peaks at 440 and 860 nm, which were enhanced with the increasing content of acid‐doped PoAN in the PVA matrix, were attributed to the radical cation and localized polaron generated in the conducting polymer. However, the peak at 620 nm was ascribed to the emeraldine base (EB) form of PoAN; that is, a portion of the acid was detached from the conducting polymer to form EB‐PoAN and free acid. The linear dependence of the logarithmic electrical conductivity on the variation of humidity, which was observed for all the composites, was caused by the salt–base transition of the conducting polymer, that is, by the movement of free acid between the active sites of the conducting polymer and the strongly bound water existing in PVA, which in turn depended directly on the environmental humidity. The response time of the composites to humidity was shortened with a decrease in the size of the dopant anions: DBSA > CSA > TSA > SA. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4343–4352, 2000     

Thermal properties of poly(anthranilic acid) (PANA) and humidity-sensitive composites derived from heat-treated PANA and poly(vinyl alcohol)

Thermal conversion of poly(anthranilic acid) (PANA) to polyaniline (PAn) has been studied by means of thermogravimetric/mass (TG/MS) and Fourier transform infrared (FTIR) spectroscopy. The electrical conductivity of the chemically prepared PANA was 3.5 × 10⁻² S/cm, which is caused by the self-doping of the polaronic nitrogen atom interacting with the ionized carboxyl group ( COO⁻). The heat-treated PANA can be assumed to be identical to an emeraldine base of PAn. The pyrolysis of PANA proceeded through the decarboxylation at two stages from carboxyl ( COOH) and ionized carboxyl groups, which occurred at about 170 and 230 °C, respectively. PANA–SA, which was prepared by treating PANA at 250 °C and then doping with an external protonic acid at room temperature, showed a considerably high conductivity (6.2 S/cm). The composite consisting of PANA–SA and poly(vinyl alcohol) was very sensitive to the environmental humidity. The logarithm of electrical conductivity of this composite was proportional to the relative humidity covering more than five orders of magnitude, and the change in conductivity extended from 4.2 × 10⁻⁵ to 10 S/cm upon the humidity variation from 14 to 91%. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 4458–4465, 1999     

Dissociation behavior of poly(α‐hydroxy acrylic acid)

Dissociation behavior of poly(α‐hydroxy acrylic acid) (PHA) was investigated by potentiometric titration in the presence of NaCl and/or divalent metal chlorides. It was found that pH values of PHA aqueous solutions increased with time when the degree of dissociation, α, is high (α ≧ 0.5 for NaCl system) and decreased in the lower α region (α < 0.5 for NaCl). The increase of pH was attributed to lactone ring formation that occurs between a carboxyl group and a neighbor hydroxyl group upon protonation to the former, and the decrease of pH to an induction effect by lactone ring to −COOH group. The pH‐increasing process was analyzed by assuming it being of a first order to obtain a time constant. On the basis of time constant thus estimated and pKa values for divalent counterion systems, a correlation between counterion binding and lactone ring formation was discussed. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 1523–1531, 1999     

Matrix-free high-resolution imaging mass spectrometry with high-energy ion projectiles

The importance of imaging mass spectrometry (MS) for visualizing the spatial distribution of molecular species in biological tissues and cells is growing. We have developed a new system for imaging MS using MeV ion beams, termed MeV-secondary ion mass spectrometry (MeV-SIMS) here, and demonstrated more than 1000-fold increase in molecular ion yield from a peptide sample (1154 Da), compared to keV ion irradiation. This significant enhancement of the molecular ion yield is attributed to electronic excitation induced in the near-surface region by the impact of high energy ions. In addition, the secondary ion efficiency for biologically important compounds (>1 kDa) increased to more than 10(10) cm(-2), demonstrating that the current technique could, in principle, achieve micrometer lateral resolution. In addition to MeV-SIMS, peptide compounds were also analyzed with cluster-SIMS and the results indicated that in the former method the molecular ion yields increased substantially compared to the latter. To assess the capability of MeV-SIMS to acquire heavy-ion images, we have prepared a micropatterned peptide surface and successfully obtained mass spectrometric imaging of the deprotonated peptides (m/z 1153) without any matrix enhancement. The results obtained in this study indicate that the MeV-SIMS technique can be a powerful tool for high-resolution imaging in the mass range from 100 to over 1000 Da.     

Oxidation Reactivity of Bis(μ‐oxo) Dinickel(III) Complexes: Arene Hydroxylation of the Supporting Ligand

In the nick(el) of time : Bis(μ‐oxo) dinickel(III) complexes 2 (see scheme), generated in the reaction of 1 with H₂O₂, are capable of hydroxylating the xylyl linker of the supporting ligand to give 3 . Kinetic studies reveal that hydroxylation proceeds by electrophilic aromatic substitution. The lower reactivity than the corresponding μ‐η²:η²‐peroxo dicopper(II) complexes can be attributed to unfavorable entropy effects.