Effects of poly(ethylene glycol) (PEG) concentration on the permeability of PEG-grafted liposomes

Poly(ethylene glycol)-grafted liposomes (PEG-liposomes) were prepared from dipalmitoylphosphatidylcholine (DPPC) with various amounts of distearoyl-N-monomethoxy poly(ethylene glycol)-succinyl-phosphatidylethanolamines (DSPE-PEG) with PEG molecular weights of 1000, 2000, 3000 and 5000. The effects of DSPE-PEG concentration on the permeability of PEG-liposomes were investigated using carboxyfluorescein (CF). In the gel state, the CF leakage from PEG-liposomes was decreased with increasing mole fractions of DSPE-PEG for all PEG molecular weights. In the liquid-crystalline state, the CF leakage from PEG-liposomes containing DSPE-PEG1000 gradually increased with increasing mole fractions of DSPE-PEG, while that of PEG-liposomes whose molecular weight in PEG units was above 2000 rapidly decreased by the addition of DSPE-PEG. Furthermore, no effect of PEG molecular weight on CF leakage was observed. The relationship between the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) (or 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH)) and the mole fraction of DSPE-PEG for PEG-liposomes was also investigated. No significant changes in fluorescence polarization of DPH for liposomal bilayer membranes was observed in the gel and liquid-crystalline states due to the addition of DSPE-PEG, while that of TMA-DPH was decreased compared with that of liposomes without DSPE-PEG in both states.     

Studies on diacetylenic vinyl compounds. VI. ESR studies on the polymerization of diacetylene containing acrylate and methacrylates

A number of diacetylene containing acrylate and methacrylates have been synthesized and the interaction between their propagating radicals and the diacetylene groups was studied by ESR spectroscopy. In the case of polymerization at 70°C using AIBN as an initiator, the propagating radicals of methacrylates are temporarily trapped with the diacetylenes with rapid exchange of the electron, thus showing strong signals of the propagating radicals. Gamma irradiation of the frozen state produces a blue color in samples, and the ESR signals were found to be those of uninteracted acrylate and methacrylates. From a comparison of spectral widths, there seems to exist an intramolecular interaction between the radicals and the diacetylene group at the frozen state. © 1992 John Wiley & Sons, Inc.     

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.     

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.     

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.     

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.     

Regioselective synthesis and properties of novel [60]fullerene bisadducts containing a dibenzocrown ether moiety

The reactions of [60]fullerene with bis-o-quinodimethane precursors 3, 4, and 5 containing a dibenzo-18-crown-6, 24-crown-8 and 30-crown-10 moiety, respectively, were investigated. Both 3 and 4 provided trans-4 bisadducts 6a and 7a, respectively, as major product, though the selectivity in the latter was lower than that in the former. As minor product, 6b (cis-2) was produced from 3, while 7c (e) as well as 7b (cis-2) were produced from 4. Precursor 5 exclusively afforded e bisadduct 8 without any other regioisomers. These bisadducts showed different ionophoric properties from one another; for instance, 6a and 7b exhibited a high complexing ability toward the K+ ion, while 6b hardly showed complexation with any alkali metal ions. The selectivity coefficients (K(Na,K)(pot)) of 6a and 7b toward K+ over Na+ ion, determined with an ion-selective electrode, were much higher than that of dibenzo-18-crown-6.     

Diacetylene-containing polymers,II. Polyesters and polyurethanes containing m,m′-butadiynylenedibenzyl groups

Diacetylene-containing polyesters and polyurethanes were prepared by the reaction of m,m-butadiynylenedibenzyl alcohol with isophthaloyl chloride, sebacoyl chloride, hexamethylene diisocyanate and 2,4-tolylene diisocyanate. Their thermal behavior was studied by optical microscope and differential scanning calorimetry (DSC). The polyesters were crystalline. The polyurethane prepared from hexamethylene diisocyanate and polyphthalates crystallized on cooling from their melts. All turned a reddish brown color on heating at temperatures above 200°C, and prolonged heating led to a black resin, but thermal decomposition could not be avoided. Irradiation by γ-ray and UV light at room temperature deepened the color of the films, but the polymerization of the diacetylene groups was not appreciable. Simultaneous heating and irradiation was necessary to obtain transparent, amorphous, wine red colored films.