Calculation of skin permeability coefficient for ionized and unionized species of indomethacin.

The contribution of ionized and unionized species to the overall permeation of weak electrolytes through the skin was investigated to determine the effect of pH in the vehicle on the permeability of indomethacin (IDM), as a model drug, through hairless rat skin. The permeability of IDM through polydimethylsiloxane (silicone) and poly(2-hydroxyethyl methacrylate) (pHEMA) membranes which may reflect lipid and aqueous pathway, respectively, was also measured for comparison. As the pH in the vehicle increased, there was an exponential increase in the skin permeation rate of IDM. The permeation rate of IDM through the silicone membrane was constant independent of pH, whereas that through the pHEMA membrane increased with increasing pH, similar to the skin permeation. The permeability coefficients of ionized and unionized species through the skin estimated using the skin permeation rates and solubilities of IDM at various pHs were 1.50 x 10(-7) and 2.79 x 10(-5) cm/s, respectively. These results indicated that the permeation of ionized species greatly contributed to the total permeation of IDM at higher pH, and that the total permeation rate of IDM was determined by the permeation of unionized species at lower pH. These contributions depend on the pH and pKa values and the ratio of permeability coefficient of each species. It was also confirmed that the skin has at least two kinds of permeation pathways and these two species permeate through a different pathway.     

Wechselwirkung zwischen entgegengesetzt geladenen Polypeptiden

Ohne Zusammenfassung     

Palladium catalyzed synthesis of tertiary allylamines. Utilization of α-nitro olefins as allylic nitro compounds

Reaction of α-nitro olefins with secondary amines in the presence of palladium(O) catalyst affords allylic amines.     

Blue myoglobin reconstituted with an iron porphycene shows extremely high oxygen affinity

Myoglobin will be a good scaffold for engineering a function into proteins. To modulate the physiological function of myoglobin, almost all approaches have been demonstrated by site-directed mutagenesis, however, there are few studies which show a significant improvement in the function. In contrast, we focused on the replacement of heme in the protein with an artificial prosthetic group. Recently, we prepared a novel myoglobin reconstituted with an iron porphycene as a structural isomer of mesoheme. The bluish colored reconstituted myoglobin is relatively stable and the deoxymyoglobin reversibly binds ligands. Interestingly, the O2 affinity of the reconstituted myoglobin, 1.1 x 109 M-1, is a significant 1,400-fold higher than that of the native myoglobin. Furthermore, the unfavorable autoxidation kinetics show 7-fold decrease in rate for the reconstituted myoglobin relative to the native myoglobin, indicating the stable oxy-form against autoxidation. The net results come from the slow dissociation of the O2 ligand in the reconstituted myoglobin, koff = 0.11 s-1, because of the formation of strong hydrogen bond between His64 and negatively charged dioxygen. The present study indicates that the replacement of native heme with an artificially created prosthetic group will give us a unique function into a hemoprotein.     

La luminescence différée du styrène en solution vitreuse dans le méthylcyclohexane

The trapping of electrons and styrene cations and anions has been studied in a methylcyclohexane glass by the techniques of deferred luminescence. Radiothermoluminescence curves consist of two peaks, at 90 and 95°K, in this matrix. The second peak increases linearly with styrene concentration up to 2 × 10^?2M when it reaches a constant value, whereas the first peak increases from 10^?4 to 10^?3M and then decreases at higher concentrations and is not discernible at concentrations above 10^?2M. We propose two mechanisms which are qualitatively consistent with this behavior and are based essentially on the recombination of styrene cations with thermally detrapped electrons in the first peak and with anions in the second peak. Photothermoluminescence (i.e., thermoluminescence after photoionization with ultraviolet light) similarly consists of the 90 and 95°K peaks for a 10^?3M solution and of the 95° peak alone for a 10^?d M solution. Radiophotoluminescence excitation spectra at 77°K, corresponding to absorption spectra of trapped electrons and styrene anions, show that anions are the predominant negative species in 10^?2 molar solution, and trapped electrons in 10^?3 molar solution. Spectral analysis of radiothermoluminescenece shows the presence of two emission bands, one of which is identical with styrene fluorescence excited by the 254 Nm mercury line (λ_max = 292, 302, 307, and 317 Nm). The other band has three fairly poorly resolved maxima at 474, 486 and 496 nm and seems to correspond to the fluorescence of C₆H₅?H-CH₃ radicals formed during radiolysis.     

Photoinduced ionic polymerization. III. Cationic polymerization and copolymerization of cyclohexene oxide and α-methylstyrene in the presence of pyromellitic dianhydride

The photoinduced ionic polymerization of cyclohexene oxide was studied in the presence of pyromellitic dianhydride. The polymerization is initiated by the excited chargetransfer complex between cyclohexene oxide and the electron-acceptor and proceeds by a cationic mechanism. Photoinduced cationic polymerization of α-methylstyrene was also observed in the presence of pyromellitic dianhydride. The initiation mechanism of the polymerization was elucidated by means of electron spin resonance measurements. The concentration of pyromellitic dianhydride anion-radicals measured in this way was found to be proportional to the rate of polymerization. This result shows clearly that the photopolymerization is initiated by cation-radicals formed from photoexcited donoracceptor complexes. The attempted photocopolymerization of cyclohexene oxide and α-methylstyrene gave a mixture of homopolymers. The composition of the product depends on the wavelength of the light used.     

Radiation-induced solid-state polymerization of trioxane under high pressure

The in-source polymerization of trioxane in the solid state was investigated over a wide range of temperature and pressure, i.e., from 30 to 140°C and up to 7000 kg/cm², respectively. In the polymerization that was carried out slightly below the melting point under pressure, the higher the pressure, the higher the rate of polymerization. It was confirmed that the maximum rate of solid-state polymerization of trioxane occurs near the melting points, even under elevated pressure. The rate of polymerization decreased with increasing pressure at constant temperature. The shape of the time–conversion curves may be classified into two types, i.e., one which is typical of high pressure and low temperature, and the other which is typical of low pressure and high temperature. Changes in the shape of the conversion—intrinsic viscosity curves occurred coincidentally. Thus, three regions for the different “polymerization characteristic” were determined as functions of polymerization temperature and pressure. Explanations are given for the above-mentioned polymerization characteristic.     

Prediction of measurement precision of apparatus using a chemometric tool in electrochemical detection of high-performance liquid chromatography

The relative standard deviation (RSD) of measurements in high-performance liquid chromatography with electrochemical detection (HPLC-ECD) was predicted by a chemometric tool based on the 1/f fluctuation model which is made up of white noise and a Markov process, called the Function of Mutual Information (FUMI) theory. FUMI theory can provide aprecise and reliable detection limit from a single measurement of noise and signal in HPLC-ECD. To obtain RSD (n = 5) for determination of (-)-epicatechin at five concentrations required 12.5 h, while the predicted RSD by FUMI theory required only 0.5 h (one measurement). Moreover, to trace the source of instrumental noise, power spectra of chromatographic baseline were used. Selection of a suitable apparatus in HPLC-ECD system, acquisition of RSD, and detection limits for determination of catechins by HPLC-ECD were simply and easily made by this chemometric tool within a very short time. The use of the FUMI theory for the prediction of measuring precision was more efficient and the optimization was less time-consuming to be suited for determination.     

Crossed molecular beam chemiluminescence study of the metastable mercury reaction: Hg(3P)+Br2 → HgBr(B) + Br

Chemiluminescence from HgBr(B) formed in the reaction of Hg(6³P_o with Br₂ has been observed using a N₂-seeded nozzle beam of metastable Hg³P_o) atoms. The cross section has been estimated to be 3⁺³_?2 at a collission energy of 0.33 eV. This value is smaller by more than an order of magnitude than the corresponding value for Hg(³P₂) atoms measured by Krause et al., in accordance with their inference based on less direct evidence.     

A highly stereoselective synthesis of the C10–C31 (BCDEF ring) portion of pinnatoxin A

An efficient, highly stereoselective synthesis of the C10–C31 (BCDEF ring) portion of pinnatoxin A has been achieved utilizing tandem double hemiketal formation/intramolecular hetero-Michael addition to construct the 6,5,6-dispiroketal (BCD ring) system and subsequent intramolecular ketalization to form the 5,6-bicycloketal (EF ring) system as key steps.