Crystal structures of cyclodextrin complexes with chiral molecules

The chiral recognition by cyclodextrins and permethylated cyclodextrins have been investigated on the basis of the X-ray data of crystalline inclusion complexes. The macrocyclic ring of - and -cyclodextrin shows a round and symmetrical structure. -Cyclodextrin includes racemic 1-phenylethanol with the statistical disorder of the hydroxyl group. A pair of the R- and S-isomers of flurbiprofen are included within the cylindrical cavity formed by dimeric -cyclodextrin molecules with a head-to-head arrangement. The macrocyclic ring of permethylated cyclodextrins is remarkably distorted from the regular polygonal symmetry and has more flexibility in the conformational change than cyclodextrins. Owing to the distorted conformation and steric hindrance involving methyl groups, permethylated cyclodextrins do not equally include both isomers, as demonstrated by the permethylated -cyclodextrin complexes with mandelic acids. Permethylated -cyclodextrin binds D-mandelic acid more tightlyvia a host-guest hydrogen bond and induced-fit conformational change. Permethylated -cyclodextrin forms a hydrated crystalline complex with R-flurbiprofen, but S-flurbiprofen forms a non-hydrated crystalline complex. Significant differences between the two complexes are found in the orientation of the phenyl group and hydrogen-bond formation involving the carboxyl group.     

Effect of 2-Hydroxypropyl-β-cyclodextrin on Release Rate of Metoprolol from Ternary Metoprolol/2-hydroxypropyl-β-cyclodextrin/Ethylcellulose Tablets

The effect of 2-hydroxypropyl--cyclodextrin (HP--CyD) on the release of a water-soluble ₁-selective adrenoreceptor antagonist, metoprolol (Met), from ternary Met/HP--CyD/ethylcellulose (EC) tablets was investigated. The release rate of Met from the ternary tablets was dependent on amounts of HP--CyD in the tablets, i.e., the rate decreased when small amounts of HP--CyD were added, while large amounts of HP--CyD accelerated the rate. The slowest rate was observed for the tablet consisted of a 30/10/60 weight ratio of Met/HP--CyD/EC. The analyses of the release rates by the Korsmeyer equation and their temperature dependence suggested that Met is released from the EC matrix containing HP--CyD according to the diffusion-controlled mechanism. The water penetration studies and the micro- and macroscopic observations suggested that the retarding effect of HP--CyD is attributable to a viscous gel formation in small pores on the surface of the tablets, where HP--CyD gels may work as a barrier for the water penetration into the tablets and the release of the drug from the tablets. The in-vitro release property of the ternary tablets was reflected in the in-vivo absorption profile in dogs. The results indicated that a combination of HP--CyD and EC is useful for the release control of water-soluble drugs such as Met.     

Correlation of the number of thiophene units with structural order and carrier mobility in unsubstituted even- and odd-numbered alpha-oligothiophene films

We investigate the correlation of the number of thiophene units with the structural order and carrier mobility of the films through studies on thin-film transistors (TFTs) based on alpha-quinquethiophene (5T), alpha-sexithiophene (6T), and alpha-septithiophene (7T). The X-ray diffraction (XRD) data of the nT films deposited at low substrate temperatures present obviously different structural orders depending on the parity of the number of thiophene units. Although even-numbered nT films present well-ordered structures and large carrier mobilities, odd-numbered nT films present two different crystalline polymorphs and vastly low carrier mobilities reflecting the coexistence of two crystalline polymorphs. However, the XRD data of both even- and odd-numbered nT films deposited at high substrate temperatures indicate that the nT molecules form single well-ordered structures. Those ordered TFTs exhibit large carrier mobilities accompanying an increase in the number of thiophene units, 0.05, 0.08, and 0.13 cm2 V(-1) s(-1) for 5T, 6T, and 7T, respectively. The parity of the number of thiophene units affects the structural order intrinsically in grown thin films, and affects carrier mobilities extrinsically in their TFTs.     

Prolonged Retention of Doxorubicin in Tumor Cells by Encapsulation of γ-Cyclodextrin Complex in Pegylated Liposomes

For further increase of retention of doxorubicin (DOX) in tumor cells, we prepared the pegylated liposomes entrapping the complex of DOX with γ-cyclodextrin (γ-CyD) (complex-in-liposome), and then examined the physicochemical properties and the in vitro cellular uptake/release, compared with those of pegylated liposomes entrapping DOX alone (DOX-in-liposome). The particle sizes of these liposomes were almost comparable, and the entrapment ratios of both DOX and γ-CyD in liposomes were more than 90%. The release of DOX from liposomes in the fetal calf serum (FCS) was significantly inhibited by entrapment of γ-CyD in the liposomes. The cellular uptake of DOX into Colon-26 cells, a mouse rectal carcinoma cell line, after incubation with these liposomes was almost equivalent. However, the cellular release of DOX from cells in the complex-in-liposome system was markedly slower than that in the DOX-in-liposome system. These results suggest the potential use of liposomes containing the DOX/γ-CyD complex for high retention of DOX in tumor cells.     

A new toxic neoanisatin derivative from the pericarps of Illicium majus

A new toxic neoanisatin-derivative (1) was isolated from the pericarps of Illicium majus. The structure of this compound was elucidated by spectroscopic data, including the 2D COSY NMR technique. The toxicity of compound 1 is also described.     

Pseudorotaxane-like supramolecular complex of coenzyme Q10 with gamma-cyclodextrin formed by solubility method

The purpose of this study is to reveal whether Coenzyme Q10 (CoQ10) forms pseudorotaxane-like supramolecular complex with gamma-cyclodextrin (gamma-CyD). The poorly soluble complex of CoQ10 with gamma-CyD in water was prepared by the solubility method. The X-ray diffraction pattern of the CoQ10/gamma-CyD complex was different from that of the physical mixture, but almost the same as that of polypropylene glycol (PPG)/gamma-CyD polypseudorotaxane. Also, the differential scanning calorimetrical study and FT-IR study demonstrated the interaction between CoQ10 and gamma-CyD in the solid state. The 1H-NMR study and the yield study of the supramolecular complex of CoQ10 with gamma-CyD demonstrated that the stoichiometry was 5 : 1 (gamma-CyD : CoQ10). The dispersion rate of CoQ10 was markedly increased by the formation of the supramolecular complex with gamma-CyD, possibly due to submicron-ordered particle formulation. In fact, CoQ10 was found to form submicron-sized supramolecular particles with gamma-CyD, when prepared by the solubility method. Consequently, the present study showed that CoQ10 forms the pseudorotaxane-like supramolecular complex with gamma-CyD in water.     

Improvement in biopharmaceutics of prednisolone by β- and γ-cyclodextrins

Inclusion complexes of prednisolone with - and -cyclodextrins in the molar ratio of 1:2 and 2:3, respectively, were prepared, and their dissolutions, permeations through a cellophane membrane, releases from a suppository base, andin vivo absorption behaviors were examined. The apparent rates of dissolution and permeation of prednisolone were significantly increased by the formations of inclusion complexes with - and -cyclodextrins. The release of the drug from Witepsol H₁₅ suppositories was also increased by complexation. The serum levels of prednisolone following oral and rectal administrations of the cyclodextrin complexes to rabbits were higher than those of the drug alone. The enhanced initial absorption of prednisolone by cyclodextrin complexation suggested the possibility of smaller doses in prednisolone therapy.     

Release control of fragrances by complexation with β-cyclodextrin and its derivatives

The release control of fragrances, benzyl acetate (BA), citral (CR), linalool (LL), citronellol (CL) and linalyl acetate (LA), was conducted using β-cyclodextrin (β-CyD), 2-hydroxypropyl-β-CyD (HP-β-CyD) and 2,6-di-O-methyl β-CyD (DM-β-CyD). The release rate of the fragrances from 30% ethanol/water solution was significantly suppressed by the complexation with these CyDs, and the suppressing effect increased in the order of β-CyD?<?HP-β-CyD?<?DM-β-CyD. The concentration-dependent change of the release rate was quantitatively analyzed to obtain the stability constant (Kc) of the fragrance-CyD complexes. These Kc values were in good agreement with those determined by the solubility method. The results suggest that the release of fragrances can be prolonged by the complexation with β-CyDs and their effects can be controlled by choosing appropriate CyD derivatives with higher Kc values and by setting proper concentrations of the host molecules.     

Application Of Insulator-Metal Transition Of Conducting Polymers

As example of application of the insulator-metal transition in conducting polymers, electro-optic device utilizing electrochemical doping and radiation induced doping are discussed in detail.