Cationic N,N-Dimethylglycine Ester Prodrug of 2R-α-Tocotrienol Promotes Intestinal Absorption via Efficient Self-Micellization with Intrinsic Bile Acid Anion

The intestinal absorption of hydrophobic compounds is severely influenced by their transportation rate through the unstirred water layer in the intestinal lumen. A member of the vitamin E family, α-Tocotrienol (α-T3) has remarkable pharmacological effects, but its intestinal absorption is hampered due to its hydrophobicity. Here, we prepared three ester derivatives of 2R-α-T3, and we selected a suitable prodrug compound using rat plasma and liver microsomes. The micellization profile of the selected compound in the presence of taurocholic acid (TCA) was evaluated. After gastrostomy administration of the prodrug candidate or α-T3 solution containing TCA, AUC values were determined for α-T3 in plasma obtained from bile duct-ligated rats. Among the three types in the efficiency of the reconversion to the parent drug, α-T3 N,N-dimethylglycinate (α-T3DMG) was the best prodrug; α-T3DMG formed mixed micelles via ion pairs with anionic TCA. The solubility of α-T3DMG in n-octanol/water depended on its ratio to TCA. The AUC after α-T3DMG administration to ligated rats was 2-fold higher than that after α-T3 administration, suggesting a smooth interaction with intrinsic bile acids. In conclusion, utilization of the prodrug synthesized using N,N-dimethylglycine ester may be a beneficial approach to promote intestinal absorption of α-T3 via self-micellization with intrinsic bile acid.     

Effective control of gas hydrate dissociation above the melting point of ice

Direct measurements of the dissociation behaviors of pure methane and ethane hydrates trapped in sintered tetrahydrofuran hydrate through a temperature ramping method showed that the tetrahydrofuran hydrate controls dissociation of the gas hydrates under thermodynamic instability at temperatures above the melting point of ice.     

An efficient synthetic method for macrocyclic ketones by intramolecular alkylation of protected cyanohydrins,and its application to the syntheses of muscone and exaltone

A simple synthetic method for macrocyclic ketones based on intramolecular alkylation of carbanion, generated from protected cyanohydrin is reported. Subsequent mild treatment with acid and base of the cyclized products leads to macrocyclic ketones in high yields. The reaction is rapid and irreversible, and hence required short reaction time. The method was successfully applied to the syntheses of cyclohexadecanone and trans-2-cyclopentadecenone as a precursor of (±)-muscone and exaltone.     

Fluorescence quenching of versatile fluorescent probes based on strongly electron-donating distyrylbenzenes responsive to aromatic chlorinated and nitro compounds, boronic acid and Ca(2+)

The fluorescence quenching behavior of two distyrylbenzenes (DSBs) newly prepared bearing strongly electron-donating groups was investigated. Several chlorinated and nitro compounds quench the fluorescence of both DSBs with various efficiencies depending on the electron-withdrawing properties; the strongly electron-withdrawing compound, such as 2,4,5-trichlorophenol and 2,4-dinitrofluorobenzene, effectively diminish the fluorescence intensities of the DSBs. The fluorescence quenching was also detected in the interaction between the azacrown DSB and phenylboronic acid, while the fluorescence recovers by adding triethylamine. These quenching phenomena are attributed to the photo-induced electron transfer (PET) process. On the other hand, the azacrown DSB selectively interacts with Ca(2+) to decrease its fluorescence intensity, but the DSB with the dimethylamino groups did not. These results suggest a potential use of these types of compounds as sensors for strongly electron-withdrawing substances and a suitable metal cation.     

Black string perturbations in RS1 model

Keywords We present a general formalism for black string perturbations in the Randall-Sundrum 1 model (RS1). First, we derive the master equation for the electric part of the Weyl tensor E _μν. Solving the master equation using the gradient expansion method, we give the effective Teukolsky equation on the brane at low energy. It is useful to estimate gravitational waves emitted by perturbed rotating black strings. We also argue on the effect of the Gregory-Laflamme instability on the brane using our formalism.     

Mechanism of mode selection in Rayleigh—Bénard convection with free—rigid boundaries

Higher harmonic resonances with wavenumber ratio of 1:2, 1:2:3 and so on are shown to take place in Rayleigh—Bénard convection under free—rigid boundary condition. Bifurcation diagrams for two-dimensional motion are obtained for the Prandtl number P = 7. The subharmonic instability is explained by a couple of amplitude equations obtained from weakly nonlinear stability theory. A straightforward extension of the coupled amplitude equations leads to a model which consists of n amplitude equations. The mechanism of mode selection is illustrated by numerical simulations of the model equations.     

An asymmetric approach to the synthesis of trans-dihydrindandione

A three-step asymmetric approach to the synthesis of (3aS,7aS)-3a,4-dihydro-7a-methyl-1,5(7aH)-indandione in 60% enantiomeric excess is described.