Kensuke Takahashi

A proton nuclear magnetic resonance study on the release of bound water by inhalation anesthetic in water-in-oil emulsion

Water-in-oil emulsion was prepared from glycerol-alpha-monooleate, n-decane and water, and was used to analyze the behavior of bound water molecules in response to the addition of an inhalation anesthetic, enflurane. The motion of water molecules is monitored by proton nuclear magnetic resonance spectroscopy. To the first approximation, the half-height width of the proton signal of dispersed water is related to the spin-spin relaxation time and represents the motion of the water molecule. It appears that one of the two OH moieties of glycerol-alpha-monooleate forms a hydrogen bond with the water molecule in average. The half-height width of the dispersed water proton showed a maximal value when the glycerol alpha-monooleate/n-decane mole ratio was 4 X 10(-2). The cause of this maximum is not immediately clear, but it is suggested that the assembly mode of glycerol-alpha-monooleate may be different between the lower and higher concentration range. Enflurane decreased the half-height width of the dispersed water, indicating an increase in the motion of water molecules. This results demonstrates that the anesthetic weakened the hydrogen bond between water and glycerol-alpha-monooleate molecules, and released bound interfacial water. It is postulated that dehydration of the interface, as shown by the release of bound water, would interfere with the transport of current-carrying hydrated ions through membranes and may constitute a molecular mechanism of anesthesia.

Nuclear magnetic resonance spectra of carbanions : IX. Carbanions produced by reactions of methyl-substituted pyridines with n-butyllithium☆

Abstract Methyl-substituted pyridines were allowed to contact with n-butyllithium in n-hexane. The reaction products were dissolved with tetrahydrofuran (THF) or 1,2-dimethoxyethane (DME) and checked with PMR measurements. The metal-proton exchange reaction occurred at the α-methyl group. 2,4-Lutidine and 2,4,6-collidine in DME were metallated at the γ-methyl group. The metallated positions have been confirmed by chemical shift considerations. The extra charge in the prepared carbanions is largely delocalized into the aromatic ring. The methylene carbon atom in the carbanions is near sp 2 -hybridized. The two methylene protons in the α-picolyl carbanions show magnetic nonequivalence in the lower-temperature measurements.

19F-NMR study on micellar solubilization of a volatile anesthetic halothane: Dose-related biphasic interaction

Abstract Volatile anesthetics, used clinically at present, contain dipole moments in their molecular structure. Although the hydrocarbon core of lipid membranes is proposed to be the anesthetic action site, it is inconceivable that these dipolar molecules mix with highly structured membrane lipids isotropically. Because of the amphiphilicity, these anesthetics are most likely to associate with the hydrophilic polar surface of macromolecules. The present communication deals with the solvation mode of halothane (CF3CHClBr) to sodium dodecyl sulfate micelles estimated by 19F-NMR chemical shifts. Depending upon the halothane concentration, two different modes of halothane interacton with the micelles were identified. At low concentrations, halothane solvated onto the micellar surface according to the Langmuir adsorption isotherm. The binding became temporarily saturated when the halothane concentration was about one-half of the surfactant concentration. When halothane was added further, they started to bind the micelle again, without changing the micellar size. The final number of halothane molecules solvated onto the micelles was about equal to the number of surfactant molecules taht forms the micelle. Apparently, half of the hydrophilic parts on the micellar surface are immediately available for the anesthetic binding. When these sites are filled by the anesthetic molecules, the property of the remaining hydrophilic sites must have been changed. Halothane molecules may bind these modified sites. Another possibility is the condensation kinetics where the bound halothane molecules became the novel binding sites.

Molecular orientation of volatile anesthetics at the binding surface: 1H- and 19F-NMR studies of submolecular affinity

The shift of 1H- and 19F-NMR peaks in the frequency domain was used to resolve the solubilization of volatile anesthetics into sodium dodecylsulfate micelles to submolecular level. Enflurane has protons at both ends of the molecule, and the solubilization parameters (partition coefficients in a broad sense) of each end were estimated by 1H-NMR. The values were: 2130 for the hydrophobic end and 1980 for the hydrophilic end. The hydrophobic end of halothane is CF3, hence 19F-NMR was used: 4330 for the hydrophobic end and 2670 for the hydrophilic end. The ratios of the solubilization parameters between hydrophobic and hydrophilic ends were methoxyflurane 1.9 (Kaneshina et al. (1981) Biochim. Biophys. Acta 647, 223-226), enflurane 1.1, and halothane 1.6. The results indicate that methoxyflurane and halothane adsorb perpendicular to the membrane surface, whereas enflurane molecules stay parallel to the interface. The averaged solubilization parameters of both ends of these anesthetics were in good agreement with their conventional partition coefficients between dipalmitoylphosphatidylcholine (DPPC) membranes and water. The solubilization parameter of chloroform (1H-NMR) was 1580 in agreement with the reported values of DPPC-water partition coefficient.

[8+2]-Type cycloaddition reactions of N-aryl-2,4,6-cycloheptatriene-1-imines and 2,4,6-cycloheptatriene-1-thione with p-toluene-sulfonyl isocyanate: formation of 1,3-diazaazulanones

Reactions of N-aryl-2,4,6-cycloheptatriene-1-imines and 2,4,6-cycloheptatriene-1-thione with p-toluenesulfonyl isocyanate gave [8+2]-type cycloadducts in good yields. Eliminations of tosyl groups and dehydrogenations of the adducts afforded 1,3-diazaazulanones

Addition Reactions of 8-Aryliminotropones with Carbon Disulfide to Give Thiazolidine-2-thione and 4-Thiazoline-2-thione Derivatives

[8 π +2 π ]-Type cycloaddition reactions of 8-aryliminotropones with carbon disulfide proceeded quantitatively to afford thiazolidine-2-thione derivatives, which turned to 4-thiazoline-2-thione derivatives via 1,5-hydrogen shift upon further heating

Reactions of azepine and diazepine derivatives with palladium acetate in benzene: a novel skeletal rearrangement of azepine derivatives

Abstract Reactions of azepine derivatives with palladium acetate in benzene give the bicyclo[4.1.0]-3-azahepta-4-ene derivatives, although one diazepine derivative underwent ring-opening. A cycloheptatriene derivative yielded a phenylated product.

Synthesis and properties of norcaradiene-cycloheptatriene system fused with isoxazole ring

A partir daryl-3 oxo-4 cyclohepta [d] isoxazoles, synthese des derives chloro-4 dihydro-5,6; la dechlorhydratation de ces composes conduit aux aryl-3 dihydro-4,5 benzisoxazoles-1,2; etude par RMN 1 H de leur isomerisation de valence en aryl-3 cyclohepta [d] isoxazoles

Studies of aqueous resins

SummaryPolyesters were modified by introducing small amounts of sodium sulfonate groups as hydrophilic groups in their backbones. Stable aqueous dispersions of the polyesters could be obtained by using 2-butoxyethanol (BEA) as a cosolvent. To clarify the role of the cosolvent, they were separated into two layers, polymer and supernatant layers, byultracentrifugation. Cosolvent contents were found to be different in the former and latter layers; i.e., the contents of BEA in the former layer are low in the case of crystalline polyesters and high in the case of noncrystalline ones. Characteristics of the dispersions such as viscosity are strongly affected by the content of the cosolvent.

Formations of 1,1'-biazaazulanones through [8+2]-type cyclo-addition reactions of tropone azine with heterocumulenes

Reaction of N-aryl-2,4,6-cycloheptatrien-1-imine with hydrazine afforded tropone azine, which reacted with chloroketenes to give 1,1-biazaazulanones via [8+2]-type cycloadducts followed by elimination of hydrochloride. The similar reaction using phenyl isocyanate afforded a [8+2]-type 1:2 cycloadduct, while the reaction with phenyl isothiocyanate yielded only a 1:1 cycloadduct. 15 N and 13 C nmr spectra on C=N bond of tropne azine showed a minor contribution of a dipolar structure compared with the case of N-aryl-2,4,6-cycloheptatrien-1-imines