Synthesis and structure-activity relationships of N-substituted 2-[(2-imidazolylsulfinyl)methyl]anilines as a new class of gastric H+/K(+)-ATPase inhibitors.

A series of N-substituted 2-[(2-imidazolylsulfinyl)methyl]anilines (3) was synthesized and evaluated for its biological activity against gastric H+/K(+)-ATPase prepared from rabbit stomach and gastric acid secretions in Heidenhain pouch dogs. Monoalkyl substituents on the nitrogen atom of the aniline moiety markedly inhibited the enzyme activity to the same degree as omeprazole, a representative H+/K(+)-ATPase inhibitor. Most of these compounds, administered at 3 mg/kg i.v. inhibited histamine-stimulated gastric acid secretion. The inhibitory activity of these derivatives on the enzymes at pH 6.0 was more potent than that at pH 7.4, and was distinctly correlated to stability in aqueous solution at pH 5.0.     

Crosslinked poly(N-isopropylacrylamide) gel for electrophoretic separation and recovery of substances

Crosslinked poly(N-isopropylacrylamide) gel was tested on the feasibility for a preparative electrophoretic matrix. Horse heart myoglobin and bovine hemoglobin were well separated on the gel matrix electrophoretically by molecular sieving effect of the gel network. Relative mobilities of those proteins in the gel were larger than those in a crosslinked polyacrylamide gel of the same polymer concentration. After the separation, the protein-containing portion of the gel underwent swelling at 4°C and deswelling at 37°C, alternatively. As a result of the deswelling, each protein was recovered in a discharged solution out of the gel at almost 100% yield.     

Simple and rapid determination of hydrogen peroxide using phosphine-based fluorescent reagents with sodium tungstate dihydrate.

A simple batch method for the fluorometric determination of hydrogen peroxide using phosphine-based fluorescent reagents has been developed. A rapid, mild and selective derivatization reaction was achieved by adding sodium tungstate dihydrate to the reaction mixture of hydrogen peroxide and a phosphine-based fluorescent reagent. When 4-diphenylphosphino-7-methylthio-2,1,3-benzoxadiazole was used as a reagent, the derivatization reaction was completed after 2 min at room temperature. The calibration curve was linear between 12.5 and 500 ng hydrogen peroxide in a 10 microL sample solution. This method is accurate and has potential for on-line applications.     

On the correlation between NQR frequency and bond length in I3−

A linear correlation between the NQR frequency of the terminal iodine atom and the corresponding I-I bond length in I₃^? was found in several compounds containing triiodide anions. A simple extended Huckel MO calculation suggested that such a correlation can be used to check the validity of wavefunctions of iodine.     

Photo-initiated base-formation in a polymer matrix

It was found that amines were formed efficiently by the photolysis of O-acyloximes followed by hydrolysis in polystyrene films and the relationship between structures of O-acyloximes and yields of amines were investigated. O-phenylacetyl acetophenone oxime (PaApO), O-pivaloyl acetophenone oxime (PApO), and O-benzoyl acetophenone oxime (BApO) as monofunctional O-acyloximes and O,O′-succinyl diacetophenone oxime (SDApO) and O,O′-glutaryl diacetophenone oxime (GDApO) as bifunctional O-acyloximes were examined. The yields of amines for PaApO and SDApO under N₂ were ca. 70%, which was the highest among O-acyloximes examined in this experiment. On the other hand, the yields for PApO, BApO, and GDApO were less than 15% and it was verified that the hydrogen abstraction by imino radicals via 6-membered cyclic intermediates resulted in the lowering of yields. Although the effect of oxygen under photolysis on the yields of amine for PaApO was negligible under 50% conversion of PaApO, the yield decreased with further increase in the conversion and was 50% at 90% conversion. © 1994 John Wiley & Sons, Inc.     

Effect of freezing rate on physical stability of lyophilized cationic liposomes

Factors affecting the storage stability of lyophilized cationic liposomes were investigated using liposomes prepared with various excipients and by different freezing rates, either quick freezing (freezing by immersion into liquid nitrogen) or slow freezing (cooling to -50 degrees C at a rate of -10 degrees C/h). Increases in the particle size of cationic liposomes observed during freeze-drying were inhibited by the addition of sucrose, trehalose and sucrose-dextran mixtures (1 : 1 and 2 : 1 by weight). The storage instability of the formulations, as indicated by changes in particle size, was affected by their glass transition temperature (T(g)). Addition of high-T(g) excipients resulted in smaller increases in the particle size, indicating improvement of storage stability. The storage stability of cationic liposome formulations was also affected by freezing rate. Formulations prepared by slow freezing exhibited better stability. Longer shear relaxation times were observed for formulations prepared by slow freezing compared with those prepared by quick freezing. This indicates that formulations prepared by slow freezing have a lower matrix mobility, which may result in better storage stability. T(g) or (1)H-NMR relaxation measurements could not detect differences in matrix mobility between formulations prepared by different freezing rates. Shear relaxation measurements seem to be a useful method for evaluating the storage stability of cationic liposome formulations.     

Conformation-dependent change in antitumor activity of linear and branched (1----3)-beta-D-glucans on the basis of conformational elucidation by carbon-13 nuclear magnetic resonance spectroscopy.

The antitumor activity of (1----3)-beta-D-glucans was tested in order to clarify its conformation-dependent response together with conformational elucidation by carbon-13 nuclear magnetic resonance (13C-NMR) spectroscopy. It was shown that the following three conformations, single chain, single helix and triple helix, are readily distinguished by the high-resolution solid-state 13C-NMR method. It turned out that preparations of linear (1----3)-beta-D-glucans of a triple helical conformation were ineffective in the inhibition of tumor growth. These linear (1----3)-beta-D-glucans were converted to an effective form in the inhibition of tumor growth when they were lyophilized from dimethyl sulfoxide (DMSO) solutions as a result of a conformational change from the triple helical to the single chain forms. They were not effective, however, when assayed in DMSO solution. In contrast, it was found that a branched (1----3)-beta-D-glucan is effective not only in either saline solutions of the triple helical sample or the lyophilized sample from DMSO, but also in DMSO solution. The aforementioned drastic change in antitumor activity was interpreted in terms of resulting conformational changes as analyzed by the 13C-NMR method.