Molecule-Responsive Fluorescent Sensors of α-Helix Peptides Bearing α-Cyclodextrin, Pyrene and Nitrobenzene Units in Their Side Chains

-Helix peptides bearing one unit of -cyclodextrin (-CD), one unit of pyrene and one unit of nitrobenzene (NB) in their side chains have been designed and synthesized as novel molecule-responsive devices.In both the CD-peptides, -PR17 and -PL17, the NB unit is separated from the CD unit by two turns of the helix. Two reference peptides (PL17, and -P17,) have also been synthesized. The circular dichroism studies in the peptide absorption region (200–250 nm)of -PR17 and -PL17 suggestthat the CD-peptides form stable-helixstructures (83–77%), which was destabilized by accommodating guest molecules (e.g., n-pentanol) into the CD cavity. It suggests that formation of intramolecular host–guest(CD–NB) complex stabilized thehelical structure and exogenous guest molecule excluded the appending NB moiety from inside to outside of the CD cavity, thereby causing destabilization of the helical structure and increasing the random coil content. The ICD spectra of the peptides in the pyrene and nitrobenzene absorption region (250–40 nm) suggest that NB forms inclusion complex with CD. The fluorescence studies revealed that the fluorescence of the pyrene unit is quenched by the NB unit in -PR17 and -PL17. The fluorescence intensity increases with increasing guest concentration for the CD-peptides.This guest-responsiveenhancement in the fluorescence intensity can be explained in terms of increased distance between the pyrene and NB moieties, which is caused by exclusion of the NB moiety from the CD cavity by guest accommodation. Using the guest-responsive fluorescence quenching properties of the CD-peptides, we have obtained binding constants for various short chain alkanols. -PL17 has higher binding affinity to the guest molecules than its isomer, -PR17, indicating that the location of functional groups on the peptide scaffold is important in molecule detection.     

Three new quassinoids,ailantinol E,F, and G,from Ailanthus altissima

Three new quassinoids, ailantinol E (1), ailantinol F (2), and ailantinol G (3), and related compounds were isolated from Ailanthus altissima grown in Taiwan. Their structures were elucidated from spectral evidence. Each new quassinoid was evaluated for its antitumor promoting effects against Epstein-Barr virus early antigen activation introduced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. The new quassinoids were found to show potent activity without showing any cytotoxicity. The screening for inhibitors against nitric oxide donor action was also conducted using the new quassinoids and some standard samples.     

Chromium- and tungsten-triggered valence isomerism of cis-1-acyl-2-ethynylcyclopropanes via [3,3]sigmatropy of (2-acylcyclopropyl)vinylidene-metal intermediates.

The reaction of cis vicinal acetylethynylcyclopropanes 1 with a catalytic amount of M(CO)5(THF) (M = Cr or W) in the presence of Et3N at room temperature gave ortho-substituted phenols 7 in good yields as valence isomerized products. In the absence of Et3N the reactions did not work at all. The reaction of a cyclopropane having an ester or an amide instead of an acetyl moiety with M(CO)5(THF) did not take place, whereas an ethynylvinylcyclopropane gave a mixture of 1- and 2-substituted 1,3,5-cycloheptatrienes. These valence isomerization reactions are assumed to proceed via the formation of vinylidene-metal intermediates 2 from terminal alkynyl moieties followed by [3,3]sigmatropy of 2 to give seven-membered carbene complexes 3.     

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules

The release properties of phenylpropanolamine hydrochloride (PPA) from ethylcellulose (EC, ethylcellulose 10 cps (EC#10) and/or 100 cps (EC#100)) matrix granules prepared by the extrusion granulation method were examined. The release process could be divided into two parts, and was well analyzed by applying square-root time law and cube root law equations, respectively. The validity of the treatments was confirmed by the fitness of the simulation curve with the measured curve. At the initial stage, PPA was released from the gel layer of swollen EC in the matrix granules. At the second stage, the drug existing below the gel layer dissolved, and was released through the gel layer. Also, the time and release ratio at the connection point of the simulation curves was examined to determine the validity of the analysis. Comparing the release properties of PPA from the two types of EC matrix granules, EC#100 showed more effective sustained release than EC#10. On the other hand, changes in the release property of the EC#10 matrix granule were relatively more clear than that of the EC#100 matrix granule. Thus, it was supposed that EC#10 is more available for controlled and sustained release formulations than EC#100.     

Release from or through a wax matrix system. V. Applicability of the square-root time law equation for release from a wax matrix tablet

To obtain basic and clear release properties, wax matrix tablets were prepared from a physical mixture of drug and wax powder at a fixed mixing ratio. Properties of release from the single flat-faced surface, curved side surface, and/or whole surface of the wax matrix tablet were examined. Then tortuosity and the applicability of Higuchi's square-root time law equation were examined. The Higuchi equation well analyzed the release processes of different release manners. However, the region fitted to the Higuchi equation differed with the release manner. Tortuosity obtained with release from the single flat-faced surface and curved side surface was comparable with that obtained with the release from a reservoir device tablet, whereas tortuosity obtained with release from the whole surface was larger. As the wax matrix tablets were prepared at a fixed mixing ratio, their internal structures should be similar. Therefore changes in the matrix volume or volume fraction with release were examined, and an extra volume where dissolved drug stray becomes large with release time in the case of release from the whole surface. These factors should be taken into account for evaluation of applicability and release properties. Furthermore, the entire release process should be analyzed using a combination of the square-root time law and other suitable equations in accordance with release manner or condition.     

Interaction between peroxide ion and phenol group which are coordinated to the same iron(III) ion

We have prepared several new iron(III) complexes with ligands which contain a phenol group; these are tetradentate [(X-phpy)H, X and H(phpy) represent the substituents on the phenol ring and N,N-bis(2-pyridylmethyl)-N-(2-hydroxybenzyl)amine, respectively] and pentadentate ligands [(R-enph-X)H; R=ethyl(Et) or methyl(Me) derivative and H(Me-enph) denotes N,N-bis(2-pyridylmethyl)-N″-methyl-N″-(2″-hydroxyl-benzylamine)ethylenediamine] and have determined the crystal structures of Fe(phpy)Cl₂, Fe(5-NO₂-phpy)Cl₂, and Fe(Me-enph)ClPF₆, which are of a mononuclear six-coordinate iron(III) complex with coordination of one or two chloride ion(s). These compounds are highly colored (dark violet) due to the coordination of phenol group to an iron(III) atom. When hydrogen peroxide was added to the solution of the iron(III) complex, a color change occurs with bleaching of the violet color, indicating that oxidative degradation of the phenol moiety occurred in the ligand system. The bleaching of the violet color was also observed by the addition of t-butylhydroperoxide. The rate of the disappearance of the violet color is highly dependent on the substituent on the phenol ring; introduction of an electron-withdrawing group in the phenol ring decreases the rate of bleaching, suggesting that disappearance of the violet band should be due to a chemical reaction between the phenol group and a peroxide adduct of the iron(III) species with an η¹-coordination mode and that in this reaction the peroxide adduct acts as an electrophile towards phenol ring. The intramolecular interaction between the phenol moiety and an iron(III)-peroxide adduct may induce activation of the peroxide ion, and this was supported by several facts that the solution containing an iron(III) complex and hydrogen peroxide exhibits high activities for degradation of nucleosides and albumin.     

Release from or through a wax matrix system. IV. Generalized expression of the release process for a reservoir device tablet

Generalization of the release process through the wax matrix layer was examined by use of a reservoir device tablet. The wax matrix layer of the reservoir device tablet was prepared from a physical mixture of lactose and hydrogenated castor oil to simplify the release properties. Release through the wax matrix layer showed zero-order kinetics in a steady state after a given lag time, and could be divided into two stages. The first stage was the formation process of water channel by dissolving the soluble component in the wax matrix layer. The lag time obtained by applying the square root law equation was well connected with the amount of the matrix layer and mixed weight ratio of components in this layer. The second stage was the zero-order release process of drug in the reservoir through the wax matrix layer, because the effective surface area was fixed. The release rate constants were connected with thickness of the matrix layer and permeability coefficient, and the permeability coefficients were connected with the diffusion coefficient of drug and porosity. Hence the release rate constant could be connected with the amount of matrix layer and the mixed weight ratio of components in the matrix layer. It was therefore suggested that the release process could be generalized using the amount of matrix layer and the mixed weight ratio of components in the matrix layer.     

Synthesis of novel fullerene amino acids and their multifullerene peptides

[60]-Fullerene functionalized amino acids with 4-6 methylene spacers from α-carbon to the nitrogen atom of fulleropyrolidine and corresponding multifullerene peptides have been synthesized.     

Studies on antiulcer drugs. III. Synthesis and antiulcer activities of imidazo[1,2-a]pyridinylethylbenzoxazoles and related compounds. A novel class of histamine H2-receptor antagonists.

A series of imidazo[1,2-a]pyridinylalkylbenzoxazole derivatives was synthesized and tested for histamine H2-receptor antagonist, gastric antisecretory and antiulcer activities. Some of 2-amino-6-[2-(imidazo[1,2-a]pyridin-2-yl)ethyl]benzoxazole derivatives were found to have good pharmacological activities. Among them, 2-amino-6-[2-(7-methoxy-3-methylimidazo[1,2-a]pyridin-2-yl)ethyl] benzoxazole (II-11) and 2-acetamido-6-[2-(7-methylimidazo[1,2-a]pyridin-2-yl)ethyl] benzoxazole (II-38) showed potent antisecretory and cytoprotective activity. The structure-activity relationships of these compounds are discussed.     

Release from or through a wax matrix system. II. Basic properties of release from or through the wax matrix layer

In order to examine basic properties of release from and through wax matrix layer, reservoir device matrix tablet was prepared from a physical mixture of hydrogenated caster oil and drug that was the same one in the reservoir. Release process could be divided into two stages. The first stage was the formation process of water channel by dissolving the drug in the wax matrix layer, and dissolved drug was released from the matrix layer following the square-root-of-time law equation. Hence, the drug penetration coefficient and tortuosity in the matrix layer were estimated. The second stage was the zero order release process of drug in the reservoir through the wax matrix layer. The release rate constant was calculated from the slope of line. Hence, the drug permeability coefficient and tortuosity were estimated. Fundamentally, tortuosity can not be expressed by some meaningful factors, and is obtained as an experimental result. By preparing wax matrix system from a physical mixture other than melted granule method, it was suggested that the matrix structure was uniform three-dimensionally. As a result, tortuosity could be expressed by a function of porosity, because unrecognized factors such as the surface coverage and thickness of melted wax on the soluble component should not be involved.