Saburo Neya

Quantitative estimation of the bitter taste intensity of oxyphenonium bromide reduced by cyclodextrins from electromotive force measurements.

The bitter taste of oxyphenonium bromide, an antiacetylcholine drug, is suppressed by cyclodextrins. The extent of the suppression can be predicted from the electromotive force measurements with an oxyphenonium bromide-selective electrode. The relationship between the bitter taste intensity and the electromotive force holds true, regardless of the kind and concentration of natural and modified cyclodextrins. This result is explicable on the basis of the observation that both the bitter taste and the electric potential are determined by the concentration of free oxyphenonium bromide. Some implications and limitations of the present approach are discussed.

Synthesis of functionalized corrphycene by copper(II)-promoted cyclization

Abstract Corrphycene bearing two peripheral ethoxycarbonyl groups was formed in 19% yield via copper(II)-catalyzed cyclization of a linear tetrapyrrole. The reaction utilizes readily available precursors and is easily performed to provide a simple access to the functionalized corrphycene.

Electrochemistry of myoglobins reconstituted with azahemes and mesohemes

Abstract The iron complexes of α-azamesoporphyrin XIII and β, δ-diazamesoporphyrin III were incorporated into apomyoglobin to obtain mono- and di-azaheme reconstituted myoglobins and their electrochemical behavior was investigated. To understand precisely the effect of introduced nitrogen atom(s) to the porphyrin backbone on electrochemical behavior of reconstituted myoglobins, iron complexes of mesoporphyrin XIII and mesoporphyrin III as well as myoglobins reconstituted with these mesohemes were also prepared and their electrochemical properties were examined. Significant positive shifts in redox potential of azahemes compared with the corresponding mesoporphyrins were observed. However, the redox potentials of azaheme reconstituted myoglobins showed no or much less positive shift compared with those of mesoheme reconstituted myoglobins, suggesting the heme environment including axial ligands of the redox center would be more important than the structure of porphyrin ring itself for determining the redox potential of reconstituted myoglobins. Azaheme reconstituted myoglobins showed larger affinity with cyanide ion than the corresponding mesoheme reconstituted myoglobins. Electron transfer kinetics measured both on an electrode and by chemical reduction with dithionite correlated well to each other and depended on the structures of hemes. Azaheme reconstituted myoglobins showed larger electron transfer than the corresponding mesoheme reconstituted myoglobins, which would be explained in terms of the change in spin-state of the heme iron for azaheme reconstituted myoglobins. Also, electron transfer reaction at an In 2 O 3 electrode showed the largest kinetics at pH 6.5 for myoglobins having aquomet type redox centers.

Effect of rapid heme rotation on electrochemistry of myoglobin

Myoglobins (Mbs) reconstituted with rotatable octamethylheme and non-rotatable etioheme were prepared and their electrochemical behavior was studied. The redox potential of octamethylheme reconstituted Mb (OMe- Mb), of which heme pops around iron-histidine (F8 -His) bond, shifted negatively by ca. 30 mV compared with non-rotatable etioheme reconstituted Mb (Etio-Mb). On the other hand, the redox potentials of octamethylheme and etioheme themselves were very similar to each other. Due to the similarity of the distal histidine side of the heme of these two reconstituted Mbs, the shifts of the redox potential would be attributable to the drastic change of the orientation of proximal histidine imidazole ring to the heme plane by heme rotation. The dissociation rate constant of cyanide ion from the ferrous heme iron (II) for OMe-Mb form at 5°C and pH 7.5 was three times faster than that of Etio-Mb. The electron transfer kinetics of these Mbs showed that the heme rotation causes faster electron transfer rates in both electrode reaction and chemical reduction in solution with dithionite. The obtained heterogeneous electron transfer rates constants at an In 2 O 3 electrode and first-order rate constants of the chemical reduction were 12(±0.5) × 10 -4 cm s -1 , 9.8(± 1.0) s -1 for OMe-Mb and 6.0(± 0.5) × 10 -4 cm s -1 , 4.5(± 1.0) s -1 for Etio-Mb under the present experimental conditions.

Quantitative Prediction of the Suppression of Drug-Induced Hemolysis by Cyclodextrins from Surface Tension Data

The suppression of hemolysis induced with 0.7 mmol dm-3 chlorpromazine hydrochloride (CPZ) or 15 mmol dm-3 propantheline bromide (PB) by α-, β-, and γ-cyclodextrins (CyDs) is measured as a function of CyD concentration and is correlated with the surface tension of its solution determined at 310 K. The surface tension data allow us to estimate the 1:1 and 2:1 binding constants of CPZ with CyDs as well as the dimerization constant of CPZ. The 2:1 binding constant of CPZ with γ-CyD is larger than the 1:1 binding constant, whereas the converse result is observed for the PB−γ-CyD system. This cooperative binding of CPZ to γ-CyD would be ascribed to a higher tendency of CPZ to form dimer than that of PB. Both the capabilities of CyDs for hemolysis suppression and surface tension elevation are in the order β-CyD > γ-CyD > α-CyD for 0.7 mmol dm-3 CPZ, whereas those capabilities are in the order β-CyD ≈ γ-CyD > α-CyD for 15 mmol dm-3 PB. The bitter taste reduction and surface tension elevation for a 1.5 mmol dm-3 ...