Distribution of pirarubicin in human blood.

We investigated the distribution and stability of pirarubicin in human blood obtained from 12 healthy volunteers. The distribution of pirarubicin into blood cells showed marked temperature- and concentration-dependencies and the Arrhenius plot for pirarubicin uptake in blood was biphasic. Therefore, pirarubicin appears to be taken up into blood cells by a carrier-mediated system. Pirarubicin was mainly enzymatically metabolized to pirarubicinol in blood cells, but pirarubicin was not metabolized into doxorubicin in either blood or plasma. On the other hand, in plasma, pirarubicin was degraded to unknown inactive compounds instead of pirarubicinol. It is therefore suggested that blood cells serve to protect against the degradation of pirarubicin into inactive compounds in blood. Accordingly, when the monitoring of pirarubicin and its active metabolites is carried out in patients, both blood and plasma must be frozen immediately after blood collection.     

On the Structure of Syndiotactic Poly(propylenes)

Propylene was polymerized with the catalyst system (C₂H₅)2A1C1/ VCk/ anisole at -78°C using various conditions. The resulting polymers were successively extracted by diethyl ether, hexane, and heptane, leaving the residue. The polymers of the four series were characterized by intrinsic viscosity, gel permeation chromatography, ¹³C nuclear magnetic resonance, infrared spectroscopy, x-ray diffraction, and by differential scanning calorimetry. The combined evidence from the various methods indicates that this catalyst system leads to stereoblock polymers which can be fractionated according to stereochemical composition and sequence length.     

X-ray diffraction analysis of nonequilibrium states in crystals: observation of an unstable conformer in flash-cooled crystals

Some molecules with a molecular skeleton similar to that of stilbenes and azobenzenes show orientational disorder in the crystals. If the disorder is dynamic, a conformational interconversion takes place through a pedal motion. In this study X-ray diffraction analyses of (E)-stilbene (1) and azobenzene (2) were carried out at various temperatures. We succeeded in observing thermodynamic nonequilibrium states that were generated by fast freezing of the conformational interconversion at low temperatures. The populations of the two conformers in crystals of 1 at 90 K varied with the cooling rate. Flash cooling of a crystal of 2 from room temperature to 90 K made it possible to observe the minor unstable conformer that does not exist in the equilibrium state at the same temperature.     

A modified method using static head-space gas chromatography for determining the stability constants of 1-alkanol/alpha-cyclodextrin complexation

A modification of the conventional static head-space gas chromatography method (SHSGC method) to determine stability constants for 1-alkanol/alpha-CD inclusion complexes was investigated. The 1 : 1 stability constants determined by this modified SHSGC method are in reasonable agreement with the corresponding values reported previously. The modified SHSGC method precludes the necessity of the calibration curve by the use of Henry's law constant of guest. Consequently, the modified SHSGC method is more advantageous than the conventional SHSGC method because the experimental time required for determination of the stability constant is markedly reduced.     

Role of the special pair in the charge-separating event in photosynthesis

We synthesized special-pair/electron-acceptor systems consisting of a complementary slipped cofacial dimer of imidazolyl-substituted zinc porphyrin, bearing pyromellitdiimide as the electron acceptor. In the case of the dimer, the first and second oxidation potentials were split into a total of four peaks in the differential pulse voltammetry measurement. Furthermore, the shift values of the first oxidation potentials obtained by changing the solvent polarity for the dimer were almost half of those observed for the monomer. These results indicate that the radical cation is delocalized over the whole pi system of the dimer. Time-resolved transient absorption measurements revealed that, relative to the corresponding monomer, the dimer accelerated the charge separation rate, but decelerated the charge recombination rate. The smaller reorganization energy of the slipped cofacial dimer relative to that of the monomeric system demonstrates the significance of the special-pair arrangement for efficient charge separation in photosynthesis.     

Swelling-shrinking behavior of a polyampholyte gel composed of positively charged networks with immobilized polyanions

Polyampholyte gels were prepared by free radical polymerization of aqueous monomer solutions with the following composition: 69% N-isopropylacrylamide (thermosensitive neutral monomer), 1% N,N'-methylenebisacrylamide (cross-linker), 15% 1-vinylimidazole (cationic monomer), and either 15% acrylic acid (AAc, anionic monomer) or poly(acrylic acid) (PAAc, polyanion). We thus obtained two sorts of polyampholyte gels; that is, G1 with immobilized PAAc and G2 with randomly copolymerized AAc. The equilibrium swelling ratio (Qe) was studied as a function of the pH, NaCl concentration, and temperature. Also studied was the kinetics of swelling and shrinking in response to a sudden pH change. The significant results obtained were as follows: (i) A fully collapsed state was observed at pH 4.5-9.0 for G1 and at pH 4.5-7.0 for G2. (ii) Below and above these pH ranges, both gels were in a swollen state; therefore, an isoelectric point (pI) appeared in a wide pH range. (iii) At alkaline pH regions where a hysteresis was observed in the Qe versus pH curves of G1 and G2 as the pH was first increased then decreased, G1 exhibited very slow swelling-shrinking kinetics. (iv) An increase in the NaCl concentration allowed the gel to swell at pH approximately pI (antipolyelectrolyte behavior) but to shrink at pHs below and above the pI range (polyelectrolyte behavior). (v) The magnitude of the salt-induced shrinking of G1 is smaller than that of G2 at pH 10 and at NaCl concentrations > 0.01 M. (vi) At pH 10, an increase in the temperature from 35 to 50 degrees C led to a shrinking change of G1 but not of G2. These results were found to be explicable in terms of a different distribution of negative charges within the polyampholyte gel network.     

Total Synthesis of Natural PI-091, a New Platelet Aggregation Inhibitor of Microbial Origin

The total synthesis of a new platelet aggregation-inhibiting gamma-lactam PI-091 (1) gave a 1:1 diastereomeric mixture at the gamma-ketal carbon. The high-yielding aldol reaction of an appropriately protected 1,3,4-trihydroxy-4-methyldecan-2-one 42, prepared from D-glucose, with the kinetically generated enolate of 3-methyl-2-butanone provided 43. The resulting diastereomeric mixture of the aldol adduct 43 was converted to a 2,4-alkylated furan 45 via an intramolecular ketalization followed by dehydration. The addition of a singlet oxygen to the alpha-trimethylsilylated furan 48derived from 45 under photochemical conditions efficiently provided an alpha,gamma-dialkylated gamma-hydroxy gamma-lactone 47. The transformation of methyl ketal 52 prepared from 47 into gamma-hydroxy gamma-lactam 53 was achieved by exposure to liquid ammonia in MeOH. The total synthesis of 1 was achieved from 52 through the Dess-Martin periodinane oxidation of the secondary hydroxy group in the side chain. The present total synthesis revealed that the stereogenic carbon center in the side chain in natural 1 is S.     

Evaluation of the abilities of ��-cyclodextrin to form complexes by surface plasmon resonance with a Biacore? system

Although phase-solubility studies have often been used to evaluate the interaction of cyclodextrins (CDs) with various drugs, hundreds of milligrams of both CD and drug are required to prepare a phase diagram. A method that would require considerably less material for evaluating complex formation between a CD and guest compound is therefore needed. We previously reported the detection of the interactions between ??-CD and various drugs using a Biacore^® system. In this study, we succeeded in immobilizing 6-monodeoxy-6-monoamino-??-CD on the gold surface of a sensor chip and in detecting the interactions between the immobilized ??-CD and various drugs. The interaction processes were kinetically analyzed using Biacore^®. The surface plasmon resonance sensorgrams indicated that the association and dissociation rates of the interactions between ??-CD and drugs were faster than those between ??-CD and drugs. Although the association constants calculated from the sensorgrams were smaller than those calculated from phase-solubility studies, good correlation was shown between these data.     

Reductive carboxylation of alkyl halides with CO2 by use of photoinduced SmI2/Sm reduction system

Upon visible-light irradiation, reductive carboxylation of alkyl halides takes place by using a SmI₂/Sm mixed system under atmospheric CO₂ to afford the corresponding carboxylic acids in good to excellent yields.     

Synthesis and reactions of benzopentathiepin having hydroxyl group

The synthesis of benzopentathiepin having a hydroxyl group at the neighboring position of polysulfur ring was performed by demethylation of 6-ethyl-9-methoxybenzopentathiepin with hydrogenbromide. Benzotrithiole having hydroxyl group was not isolated at all. The hydroxyl group was also alkylated with alkyl iodide in the presence of weak base.