Calculation of skin permeability coefficient for ionized and unionized species of indomethacin.

The contribution of ionized and unionized species to the overall permeation of weak electrolytes through the skin was investigated to determine the effect of pH in the vehicle on the permeability of indomethacin (IDM), as a model drug, through hairless rat skin. The permeability of IDM through polydimethylsiloxane (silicone) and poly(2-hydroxyethyl methacrylate) (pHEMA) membranes which may reflect lipid and aqueous pathway, respectively, was also measured for comparison. As the pH in the vehicle increased, there was an exponential increase in the skin permeation rate of IDM. The permeation rate of IDM through the silicone membrane was constant independent of pH, whereas that through the pHEMA membrane increased with increasing pH, similar to the skin permeation. The permeability coefficients of ionized and unionized species through the skin estimated using the skin permeation rates and solubilities of IDM at various pHs were 1.50 x 10(-7) and 2.79 x 10(-5) cm/s, respectively. These results indicated that the permeation of ionized species greatly contributed to the total permeation of IDM at higher pH, and that the total permeation rate of IDM was determined by the permeation of unionized species at lower pH. These contributions depend on the pH and pKa values and the ratio of permeability coefficient of each species. It was also confirmed that the skin has at least two kinds of permeation pathways and these two species permeate through a different pathway.     

Time decay of solutions to the cauchy problem for time-dependent Schrödinger-Hartree equations

We consider the time-dependent Schrödinger-Hartree equation (1) $$iu_t + \Delta u = \left( {\frac{1}{r}*|u|^2 } \right)u + \lambda \frac{u}{r},(t, x) \in \mathbb{R} \times \mathbb{R}^3 ,$$ (2) $$u(0,x) = \phi (x) \in \Sigma ^{2,2} ,x \in \mathbb{R}^3 ,$$ where λ≧0 and \(\Sigma ^{2,2} = \{ g \in L^2 ;\parallel g\parallel _{\Sigma ^{2,2} }^2 = \sum\limits_{|a| \leqq 2} {\parallel D^a g\parallel _2^2 + \sum\limits_{|\beta | \leqq 2} {\parallel x^\beta g\parallel _2^2< \infty } } \} \) . We show that there exists a unique global solutionu of (1) and (2) such that $$u \in C(\mathbb{R};H^{1,2} ) \cap L^\infty (\mathbb{R};H^{2,2} ) \cap L_{loc}^\infty (\mathbb{R};\Sigma ^{2,2} )$$ with $$u \in L^\infty (\mathbb{R};L^2 ).$$ Furthermore, we show thatu has the following estimates: $$\parallel u(t)\parallel _{2,2} \leqq C,a.c. t \in \mathbb{R},$$ and $$\parallel u(t)\parallel _\infty \leqq C(1 + |t|)^{ - 1/2} ,a.e. t \in \mathbb{R}.$$      

Antiviral agents of plant origin. III. Scopadulin, a novel tetracyclic diterpene from Scoparia dulcis L

The structure and stereochemistry of scopadulin, a novel aphidicolane-type diterpene isolated from Scoparia dulcis L. have been established from spectral data and single-crystal X-ray analysis of its acetone solvate.     

Radiation sterilization of enzyme hybrids with biodegradable polymers

Ionizing radiations, which have already been utilized for the sterilization of medical supplies as well as gas fumigation, should be the final candidate to decontaminate “hybrid” biomaterials containing bio-active materials including enzymes because irradiation induces neither heat nor substances affecting the quality of the materials and our health. In order to check the feasibility of ⁶⁰Co-gamma rays on these materials, we selected commercial proteases including papain and bromelain hybridized with commercial activated chitosan beads and demonstrated that these enzyme-hybrids suspended in water showed the significant radiation durability of more than twice as much as free enzyme solution at 25-kGy irradiation. Enhanced thermal and storage stability of the enzyme hybrids were not affected by the same dose level of irradiation, either, indicating that commercial irradiation sterilization method is applicable to enzyme hybrids without modification.     

Additive telluromolybdates. Structure and catalysis in oxidation

Additive telluromolybdates, MoO₃·2TeO₂ and M^IIO·TeO₂·MoO₃ (M^IITeMoO₆; M^II = Co, Mn, Zn), converted ethyl lactate selectively to pyruvate in a vaporphase fixedbed flow system at 250–300 °C. A synergy in activity was observed for binary TeO₂–MoO₃, and crystalline Te₂MoO₇ was suggested as the active species. The Rietveld analysis of powder XRD patterns of ternary CoTeMoO₆ revealed the layer structure quite different from that of the reference Te₂MoO₇, but tellurium was again located adjacent to molybdenum linked through lattice oxygen.     

Chiral β-dimethylaminoalkylphosphines. Highly efficient ligands for a nickel complex catalyzed asymmetric grignard cross-coupling reaction

Chiral β-dimethylaminoalkylphosphines were prepared starting with amino acids, (S)-alanine, (S)-phenylalanine, (R)-phenylglycine, (S)-valine, and (R)-tert-leucine. The chiral phosphines were found to be highly efficient ligands for a nickel catalyzed asymmetric Grignard cross-coupling reaction (38～94% optical yield).     

Secondary hypervalent I(III)...O interactions: synthesis and structure of hypervalent complexes of diphenyl-lambda3-iodanes with 18-crown-6

Reported here for the first time are the synthesis and characterization of supramolecular complexes between diaryl-lambda(3)-iodanes and 18-crown-6 (18C6). Slow evaporation of solvents afforded 1:1 and 2:1 complexes between Ph(2)IBF(4) and 18C6 as stable crystals, depending on the conditions. X-ray crystal structures of these complexes indicated that each iodine atom contacts with the three adjacent oxygen atoms of 18C6 through two hypervalent secondary bonding and a weak interaction. (1)H NMR analyses and CSI-MS spectra showed that, in dichloromethane solution, Ph(2)IBF(4) exclusively forms the 1:1 complex with 18C6 (binding constant K(a), 1.02 x 10(3) M(-)(1)). The binding constants decrease with the increased solvent donor ability (Gutmann's DN). Changing the heteroatom ligand from BF(4) to the less nucleophilic PF(6) and AsF(6) increased the binding constant by about six times. Substitution of an electron-withdrawing group onto the para position of Ph(2)IBF(4) tends to increase in the complex stability. A linear Hammett relationship (rho = 0.59) between log K(a) and sigma(p)(+) values of substituents indicates that the diaryl-lambda(3)-iodanes with electropositive iodine(III) interact more efficiently with 18C6. Decreased binding magnitude was measured with 15C5, dibenzo-18C6, dibenzo-21C7, and dibenzo-30C10.     

A new stereoselective synthesis of 2-subsdtituted 1,3-bis(trimethylsilyl)propene derivatives and their conversion to cyclopentane and cyclohexane derivatives

Ester $\text{2}$ on treatment with sodium salt of sulfone or sulfoxide afforded 2-substituted 1,3-bis(trimethylsily)propene $\text{3}$ in good yield, from which cyclopentane and cyclohexane derivatives bearing a trimethylsilyl group in the molecules were synthesized.     

Relieving effect of saline on cephaloridine nephrotoxicity in rats

To elucidate the mechanism(s) of the relieving effect of saline on cephaloridine (CER) nephrotoxicity, rats were given CER in equal quantity (1 g/kg body weight; i.v.), but at two different concentrations (4 and 25%) in saline. Urinary excretion of glucose, which was investigated as an index for renal proximal tubular injury, revealed that the renal damage was less in the 4% CER 25 ml/kg group than in the 25% CER 4 ml/kg group. As to urinary excretions of CER, sodium, potassium and water, no significant differences were observed between the two groups in the first 2 h, but chloride in the 4% CER 25 ml/kg group showed higher values than in the 25% CER 4 ml/kg group. Plasma concentrations of sodium, potassium, chloride and CER, did not show any definite distinctions between the two groups. At the time-point of 20 min after the CER administration, renal CER content was significantly lower in the 4% CER 25 ml/kg group than in the 25% CER 4 ml/kg group. These results suggest that the sodium ion which is needed for cellular trapping of CER is competitively expended for cellular entry of the chloride ion in the kidney, and that the relieving effect of the saline on CER nephrotoxicity is ascribable to the loaded quantity of chloride ion.     

Relaxation dynamics in glycerol-water mixtures: I. Glycerol-rich mixtures

We discuss the relaxation dynamics of glycerol-water mixtures, as studied by dielectric spectroscopy in the frequency range from 1 Hz to 250 MHz and at temperatures between 173 and 323 K. The experimental results obtained for the glycerol-rich mixtures suggest that the main dielectric relaxation process, as well as the so-called high-frequency "excess wing" (EW) and dc conductivity, follow the same temperature dependence. This result indicates that all of these processes are induced by the same molecular origin. A new phenomenological function is proposed to describe the whole dielectric spectrum in the covered frequency range, and some possible mechanisms of dielectric behaviors through the dc conductivity, the main relaxation process, and the EW are discussed.