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.     

Development and application of a new general method for the asymmetric synthesis of syn- and anti-1,3-amino alcohols

A general method is described for asymmetric synthesis of both syn- and anti-1,3-amino alcohols. The first application of metalloenamines derived from N-sulfinyl imines is reported for the highly diastereoselective addition to aldehydes. The reduction of the product beta-hydroxy N-sulfinyl imines 2 with catecholborane and LiBHEt(3) provides syn- and anti-1,3-amino alcohols with very high diastereomeric ratios. This method was found to be effective for a variety of substrates incorporating either aromatic or various aliphatic substituents. The convergent and efficient asymmetric syntheses of the two natural products, (-)-8-epihalosaline and (-)-halosaline, were also accomplished.     

Electrical conducting and magnetic properties of (ethylenedithiotetrathiafulvalenothioquinone-1,3-diselenolemethide)2.FeBr4 (GaBr4) crystals with two different interlayer arrangements of donor molecules

Two donor molecules newly synthesized, dimethylthio- and ethylenedithio-tetrathiafulvalenothioquinone-1,3-diselenolemethides (1 and 2), were used to prepare their charge-transfer (CT) salts with a magnetic FeBr(4)(-) counteranion. For 1, a low electrical conducting 1:1 salt (1.FeBr(4)) was obtained, in which molecules of 1 are tightly dimerized in a one-dimensional (1D) stacking column. On the other hand, 2 gave a 2:1 salt (2(2).FeBr(4)) as two different kinds of plate crystals (I and II). Both I and II possess similar stacking structures of molecules of 2 in each 1D column with a half-cut pipelike structure along the c axis. However, for I, the stacking columns are aligned in the same direction along the a and b axes, while for II they are in the same direction along the a axis, but in the reverse direction along the b axis, resulting in the difference in the relative arrangement of molecules of 2 and FeBr(4)(-) ions between the two crystals. The room-temperature electrical conductivities of the single crystals of I and II were 13.6 and 12.7 S cm(-)(1), respectively. The electrical conducting behavior in I was metallic above 170 K but changed to be semiconducting with a very small activation energy of 7.0 meV in the temperature range 4-170 K. In contrast, II showed the semiconducting behavior in the whole temperature range 77-285 K. The corresponding nonmagnetic GaBr(4)(-) salts with almost the same crystal structure as I and II showed definitively different electrical conducting properties in the metal to semiconductor transition temperature in I as well as in the magnitude of activation energy in the semiconducting region of I and II. The interaction between the d spins of FeBr(4)(-) ions was weak and antiferromagnetic in both I and II, but the magnitude of the spin interaction was unexpectedly larger compared with that in the FeBr(4)(-) salt of the corresponding sulfur derivative of 2 with closer contact between the neighboring FeBr(4)(-) ions. These electrical conducting and magnetic results suggest a significant interaction between the conducting pi electrons and the d spins of FeBr(4)(-) ions located near the columns or layers.     

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.     

Convenient synthesis of 3,3,3-trifluoropropenyl compounds from aromatic aldehydes by means of the TBAF-mediated Horner reaction

A simple synthesis of 3,3,3-trifluoropropenyl compounds by means of the TBAF-mediated Horner reaction is described. The reagent, 2,2,2-trifluoroethyldiphenylphosphine oxide, was readily prepared either by Arbuzov reaction of ethyl diphenylphosphinite with 2,2,2-trifluoroethyl iodide or by treating chlorodiphenylphosphine with trifluoroacetic acid and water. Treatment of the phosphine oxide with aromatic aldehydes in the presence of TBAF at room temperature afforded the corresponding 3,3,3-trifluoropropenyl compounds in good yields. The present method is very convenient for preparing 3,3,3-trifluoropropenyl compounds from aromatic aldehydes in terms of availability of the reagent, operational simplicity, and good yields of the products.     

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).     

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.