Synthesis and antiinflammatory activity of 7-methanesulfonylamino-6-phenoxychromones. Antiarthritic effect of the 3-formylamino compound (T-614) in chronic inflammatory disease models

A group of derivatives of 7-methanesulfonylamino-6-phenoxychromone (1) at the pyrone and phenoxy rings was synthesized starting with 4-chloro-3-nitroanisole and evaluated against acute and chronic inflammations in oral administration in animals. Significant potency in the rat models of carrageenin-induced edema (CPE) and adjuvant-induced arthritis (AA) was realized with 2'-fluoro and 2',4'-difluoro derivatives (9a and 9d), and 3-formylamino derivative (19a) and its 2'-fluoro and 2',4'-difluoro compounds (22a and 22d), displaying AA therapeutic effect of ED40 = 2.5-7.1 mg/kg/d for 7 d and AA prophylactic effect of 53-70% inhibition at the dosage of 3 mg/kg/d for 22 d. To identify a candidate for further pharmacological study, the five compounds were subjected to evaluation of their gastro-ulcerogenic liability, leading to selection of the fluorine-free compound 19a which did not cause acute ulceration at 300 mg/kg in oral administration in rats. Compound 19a (ED40 = 3.6 mg/kg in established AA) possessed good therapeutic efficacy against type II collagen-induced arthritis in DBA/1J mice with doses of 30 and 100 mg/kg, suggesting the development of 19a (designated T-614) as a prospective disease-modifying antirheumatic agent. In addition, a preparative-scale synthetic route to T-614 has been established.     

Partial pressure dependency of 17O/16O and 18O/16O of molecular oxygen in the mass spectrometer

A method to determine both (17)O/(16)O and (18)O/(16)O ratios for molecular oxygen with high precision by direct introduction into the mass spectrometer without gas separation is presented. Because both (17)O/(16)O and (18)O/(16)O in mixed gases have good linear correlations with their mixing ratios, these isotopic compositions can be determined without a gas-separation procedure by calibration using prepared standard gases with variable mixed ratios and by monitoring the amounts of fragment ions. Analytical precision for delta(17)O and delta(18)O of 45 and 7 per meg, respectively, were obtained. The observed partial pressure dependency of isotopic composition may be caused by isotope fractionation during admission from the ionization chamber into the flight tube of the mass spectrometer.     

Observation of the anisotropic photoinduced magnetization effect in Co-Fe Prussian blue thin films fabricated by using clay Langmuir-Blodgett films as a template

Thin films of cobalt-iron cyanide (Co-Fe Prussian blue) have been fabricated by means of the modified Langmuir-Blodgett (LB) method using a smectite clay mineral (montmorillonite). In this combined method, clay LB films play a template role in the formation of the Co-Fe Prussian blue thin layer. The films were revealed to possess a well-organized structure not only in perpendicular directions to the film surface but also in parallel directions to the film surface. The photoinduced electron transfer from the iron ion to the cobalt through the bridging cyanide in the films occurred at low temperature (8 K), similar to that in the bulk Co-Fe Prussian blue. The films clearly exhibited magnetic anisotropy with regards to the direction of the applied magnetic field. Moreover, the photoinduced magnetization effect in the films was also found to be anisotropic.     

Determination of ultratrace amounts of ruthenium(III) by the delayed autocatalytic reaction using citric acid.

A method for determination of ultratrace amounts (ppq levels) of ruthenium(III) was developed using a copper(II)-phthalocyanine-3,4',4",4"'-tetrasulfonic sodium salt (Cu-PTS) as an indicator in a potassium bromate autocatalytic reaction system. A satisfactory calibration curve of ruthenium(III) ion was obtained by the time measurement in the concentration range of 1 x 10(-13) M to 5 x 10(-12) M with the relative standard deviation (RSD) of 2.8% (n=5). The determination limits (3sigma) were 3.30 x 10(-14) M (3.34 ppq).     

Synthesis and antitumor activity of benzimidazolyl-1,3,5-triazine and benzimidazolylpyrimidine derivatives

Triamino-substituted 1,3,5-triazine and pyrimidine derivatives were synthesized and tested for antitumor activities using some human cancer cell lines and murine leukemia cell lines. All the compounds having benzimidazolyl and morpholino groups as substituents on the 1,3,5-triazine ring showed antitumor activity. Pyrimidine derivatives having the same groups as substituents also showed antitumor activity. Among them, the compounds having 1-benzimidazolyl, morpholino and cis-2,3-dimethylmorpholino groups as substituents on the 1,3,5-triazine ring or pyrimidine ring exhibited the most potent antitumor activity, and these compounds exhibited no or very weak aromatase inhibitory activity. In contrast, the compounds having imidazolyl group instead of benzimidazolyl group as a substituent on the 1,3,5-triazine ring showed a potent aromatase inhibitory activity.     

New water-soluble host molecules derived from calix[6]arene

4-Sulfonate derivatives of calix[6]arene and O-n-hexylcalix[6]arene (1a and 1b, respectively) were synthesized. Measurements using fluorescence and absorption spectral probes indicated that the cavity of calix-[6]arene can accept a naphthalene molecule but not a pyrene molecule and that (1b) has a hydrophobic cavity constructed from the aggregate of the hexyl groups while (1a) provides a reaction field apparently more polar than water. This is the first example for water-soluble host molecules derived from calix[6]arene.     

Excitations, optical absorption spectra, and optical excitonic gaps of heterofullerenes. I. C60, C59N+, and C48N12: theory and experiment

Low-energy excitations and optical absorption spectrum of C(60) are computed by using time-dependent (TD) Hartree-Fock, TD-density functional theory (TD-DFT), TD DFT-based tight-binding (TD-DFT-TB), and a semiempirical Zerner intermediate neglect of diatomic differential overlap method. A detailed comparison of experiment and theory for the excitation energies, optical gap, and absorption spectrum of C(60) is presented. It is found that electron correlations and correlation of excitations play important roles in accurately assigning the spectral features of C(60), and that the TD-DFT method with nonhybrid functionals or a local spin density approximation leads to more accurate excitation energies than with hybrid functionals. The level of agreement between theory and experiment for C(60) justifies similar calculations of the excitations and optical absorption spectrum of a monomeric azafullerene cation C(59)N(+), to serve as a spectroscopy reference for the characterization of carborane anion salts. Although it is an isoelectronic analogue to C(60), C(59)N(+) exhibits distinguishing spectral features different from C(60): (1) the first singlet is dipole-allowed and the optical gap is redshifted by 1.44 eV; (2) several weaker absorption maxima occur in the visible region; (3) the transient triplet-triplet absorption at 1.60 eV (775 nm) is much broader and the decay of the triplet state is much faster. The calculated spectra of C(59)N(+) characterize and explain well the measured ultraviolet-visible (UV-vis) and transient absorption spectra of the carborane anion salt [C(59)N][Ag(CB(11)H(6)Cl(6))(2)] [Kim et al., J. Am. Chem. Soc. 125, 4024 (2003)]. For the most stable isomer of C(48)N(12), we predict that the first singlet is dipole-allowed, the optical gap is redshifted by 1.22 eV relative to that of C(60), and optical absorption maxima occur at 585, 528, 443, 363, 340, 314, and 303 nm. We point out that the characterization of the UV-vis and transient absorption spectra of C(48)N(12) isomers is helpful in distinguishing the isomer structures required for applications in molecular electronics. For C(59)N(+) and C(48)N(12) as well as C(60), TD-DFT-TB yields reasonable agreement with TD-DFT calculations at a highly reduced cost. Our study suggests that C(60), C(59)N(+), and C(48)N(12), which differ in their optical gaps, have potential applications in polymer science, biology, and medicine as single-molecule fluorescent probes, in photovoltaics as the n-type emitter and/or p-type base of a p-n junction solar cell, and in nanoelectronics as fluorescence-based sensors and switches.     

Cyclophane-based tetra(resorcinarene) as a host for both histone and hydrophobic molecular guests

A cyclophane-based resorcinarene tetramer, which is constructed with a tetraaza[6.1.6.1]paracyclophane and four resorcinarenes bearing hepta(carboxylic acid) residues that connect the macrocycle through amide linkages, was prepared. The binding constant of the cyclophane-based resorcinarene with immobilized histone was determined to be 1.3 × 10⁷ M⁻¹ by surface plasmon resonance measurements, which was 31-fold larger than that of the resorcinarene monomer bearing octacarboxylic acids. Moreover, the cyclophane-based tetra(resorcinarene) acted as a host toward hydrophobic molecular guests such as 6-p-toluidinonaphthalene-2-sulfonate.     

Distribution and dynamics of radionuclides and stable elements in the coastal waters off Rokkasho Village, Japan, prior to the opening of a nuclear reprocessing facility

The suspended particles floating in the seawater have the ability to biologically, as well as physically adsorb radionuclides and other elements dissolved in seawater. We have studied the distribution and composition of suspended particles, as well as the state of eluted of radionuclides in the decomposition process, in the coastal waters off Rokkasho Village, where radionuclides will be discharged from a nuclear fuel reprocessing plant in the near future.     

An ab initio MO study of allene episulfide, cyclopropanethione and thioxyallyl

The electronic structures of allene episulfide, cyclopropanethione and thioxyallyl were examined by ab initio MO calculations and were compared with those of the corresponding oxygen compounds, allene oxide, cyclopropanone and oxyallyl. The difference in reactivities of allene episulfide and allene oxide was also speculatively estimated from the calculated electronic structures. The lowest singlet state of thioxyallyl was predicted to be the B₂ state, which corresponds to the σ, π-diradical. A small activation energy is required for the cyclization of the B₂ state to give allene episulfide. The A₁ singlet state lies 11 kcal mol⁻¹ higher than the B₂ singlet state and undergoes the disrotatory rotation of methylene groups to give cyclopropanethione with no activation energy.