Synthesis of well-defined polymers with protected silanol groups by atom transfer radical polymerization and their use for the fabrication of polymeric nanoparticles

Copper-mediated atom transfer radical polymerization (ATRP) of a protected silanol group-holding methacrylate, methacryloxypropyltrimethoxysilane (MOPS), was investigated. In a dry condition using carefully distilled solvent and monomer, the polymerization proceeded in a living fashion providing a low-polydispersity polymer with a predicted molecular weight. The ATRP in conjunction with the sequential monomer addition of methyl methacrylate (MMA) and MOPS afforded a block copolymer of the type PMMA-b-poly(MMA-r-MOPS). The heat treatment of a solution of the block copolymer in the presence of a catalytic amount of ammonia gave a polymeric core-shell nanoparticle with a shell of PMMA moieties and a core of the poly(MMA-r-MOPS) blocks cross-linked via the condensation of the trimethoxysilane groups of the MOPS moieties.     

Double tracer whole body autoradiography using a short-lived positron emitter and a long-lived beta emitter

We investigated glucose and amino acid metabolism in tumors and other organs using whole body autoradiography with a short-lived positron emitter and a long-lived beta emitter. The radioactive compounds used were 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) with a half life of 109.8 min and L-[methyl-14C]-methionine (14C-MET) with a half life of 5,730 years. A Donryu rat weighing about 150 g was subcutaneously inoculated at the back with experimental tumors of AH109A and AH272. 74 MBq (2 mCi) of 18F-FDG and 740 kBq (20 microCi) of 14C-MET was administered and after 30 min, the rat was sacrificed. Whole body frozen sections were obtained using autocryotome. For the 18F-FDG autoradiogram, the frozen sections were exposed to an X-ray film for 6 h. After seven days, these frozen sections were again exposed to 14C-MET for a week. Cross-contamination was minimized by adjusting the exposure time, the interval of exposures and the administered dose. The accumulation of the tracers was represented as the optical density ratio of the tissue of interest to the muscle. The tumor ratios were 12.5 for 18F-FDG and 8.6 for 14C-MET showing the highest accumulation in the whole body autoradiogram. In contrast the inflammatory tissue ratios were 1.27 for 18F-FDG and 0.77 for 14C-MET showing very low amino acid metabolism. With the present double tracer whole body autoradiogram, 18F-FDG accumulation was seen in the brain and the heart but not to the liver as against 14C-MET accumulation which was seen to the liver but not to the brain and the heart.     

Destabilization of whole skin lipid bio-liposomes induced by skin penetration enhancers and FT-IR/ATR (Fourier transform infrared/attenuated total reflection) analysis of stratum corneum lipids.

Whole skin lipid bio-liposomes (skin bio-liposomes), in size ranging from 2 to 8 microns, were prepared by a reverse phase evaporation technique using rat full thickness skin. Leakage of an encapsulated fluorescence probe, ANTS (delta-amino-1,3,6-naphthalene-trisulfonate), was measured by adding transdermal penetration enhancers (penetrants) into the medium where the skin bio-liposomes were present. Oleylamine induced a fast release of ANTS from the liposomes compared to lauryl-amine which showed a weak action. With these penetrants, the degree of ANTS release from the prepared bio-liposomes was found to correlate well with the results of frequency changes in the CH-asymmetric stretching band near 2920 cm-1 in the rat stratum corneum. The penetrant which caused relatively strong leakage of ANTS induced the significantly large shift of the peak toward the higher wave-numbers due to the perturbation in the structure of lipids of the stratum corneum. The skin bio-liposomes prepared from the rat full thickness skin could be useful in evaluating the penetrants.     

Correlation between the structure of water in the vicinity of carboxybetaine polymers and their blood-compatibility

The structure and hydrogen bonding of water in the vicinity of carboxybetaine homopolymer (poly[1-carboxy-N,N-dimethyl-N-(2'-methacryloyloxyethyl)methanaminium inner salt] (PolyCMB), and a random copolymer of CMB and n-butyl methacrylate, Poly(CMB-r-BMA), with various molecular weights were analyzed in their aqueous solutions and thin film with contours of O-H stretching of Raman and attenuated total reflection infrared (ATR-IR) spectra, respectively. The relative intensity of the collective band (C value) corresponding to a long-range coupling of O-H stretchings of the Raman spectra for aqueous solution of Poly(CMB-r-BMA) was very close to that for pure water, which is in contrast with the smaller C value in aqueous solution of ordinary polyelectrolytes. The number of hydrogen bonds collapsed by the presence of one monomer residue (N(corr) value) of PolyCMB and Poly(CMB-r-BMA) (CMB, 45 mol %) (M(w), 1.14 x 10(4) and 1.78 x 10(4), respectively) could be calculated from the C value. The N(corr) values were much smaller than those for ordinary polyelectrolytes and close to those for nonionic water-soluble polymers such as poly(ethylene glycol) and poly(N-vinylpyrrolidone). Furthermore, a water-insoluble Poly(CMB-r-BMA) with a large BMA content (M(w) = 347 kD, CMB 27 mol %) could be cast as a thin film (thickness, ca. 10 microm) on a ZnSe crystal for the ATR-IR analyses. At an early stage of sorption of water into the Poly(CMB-r-BMA) film, the O-H stretching band of IR spectra for the water incorporated in the film was similar to that for free water, which is in contrast with the drastic change in the O-H stretching band of water incorporated in polymer films such as poly(methyl methacrylate) (PMMA) and poly(n-butyl methacrylate) (PBMA). The theoretical vibrational frequency for water molecules hydrating a betaine molecule calculated by using a density functional method supported the experimental results. The adhesion of human platelets to Poly(CMB-r-BMA) films was much less than that to PMMA and PBMA. With an increase in the content of CMB residue, the number of platelets adhered to the Poly(CMB-r-BMA) film drastically decreased and then gradually increased, probably due to the increase in the roughness of the film surface. These results suggest that the carboxybetaine monomer residues with a zwitterionic structure do not significantly disturb the hydrogen bonding between water molecules in both aqueous solution and thin film systems, resulting in the excellent blood-compatibility of the carboxybetaine polymers.     

Quantitation of the benzodiazepine antagonist flumazenil in human plasma by gas chromatography-mass spectrometry

A gas chromatographic-mass spectrometric procedure has been developed for the quantitation of the benzodiazepine antagonist flumazenil in human plasma. The assay utilizes an extraction at alkaline pH with benzene-dichloroethane (80:20), selective ion monitoring, isobutane positive-ion chemical ionization mass spectrometry and stable isotope dilution. The method has been used to measure plasma concentrations of flumazenil in over 1500 clinical samples over a range of 0.5-200 ng/ml (using 2 ml of plasma).     

McMullen's conditions and some lower bounds for general convex polytopes

We give a lower bound for the number of vertices of a generald-dimensional polytope with a given numberm ofi-faces for eachi = 0,..., d/2 – 1. The tightness of those bounds is proved using McMullen's conditions. Form greater than a small constant, those lower bounds are attained by simpliciali-neighbourly polytopes.     

Laser-ionization mass-spectrometric studies on laser ablation of a nitrogen-rich polymer at 532 nm and 1064 nm

Laser-ionization Time-Of-Flight (TOF) mass-spectrometric studies have been carried out on the 532 nm and 1064 nm laser ablation products from a nitrogen-rich polymer. The polymer used had an elemental composition of C_6.0N_8.9H_3.4 and consisted of C=N, C-N, and N-H chemical bonds. The TOF mass spectra observed were composed of various peaks (150 amu) depending on the ablation laser wavelength. The primary peaks were assigned to C⁺, CN⁺, CHnN⁺ ₂ (n=1–3) and C₂H₂N⁺ ₃ for 532 nm ablation, and C⁺, C⁺ ₃, HCN⁺, HCCN⁺, CH₂NH⁺, HNCN⁺, H₃NCN⁺, and C₄H₄N⁺ ₇ for 1064 nm ablation. The flight velocity distributions with peak velocities ranging from 8.6×10³ cm/s to 3.8×10⁴ cm/s were measured for these products. The distinct velocity distributions observed between small and large products indicate the presence of two origins in the fragment ejection process from the polymer for both 532 nm and 1064 nm ablation. Furthermore, we suggest an importance of the translational energy of the fragments for the product generation in the laser plume.     

Hyperfine quantum beat of short-lived beta-emitter8Li polarized by the tilted foil technique

To disclose the basic mechanisms of nuclear polarization creation realized by the tilted foil technique, hyperfine quantum beats of the nuclear polarization of the short-lived beta-emitter⁸Li(I =2⁺,T _1/2=840 ms) were measured as a function of the distance between two tilted foils. From the observed beats of the⁸Li nuclear polarization, it was found that the Fermi-contact interaction of the⁸Li nucleus with the ground 1s-electron in LiIII plays a main role in the final stage of polarization transfer from polarized orbital electrons to the⁸Li nucleus.     

Quadrupole moment of41Sc by use of new nuclear quadrupole resonance detection

Quadrupole effects in -NMR spectra of⁴¹Sc(I =7/2^–,T _1/2=0.596 s) implanted in a TiO₂ single crystal were detected by use of a modified -NMR technique. Using the field gradient in the crystal determined by the pulsed-Fourier-transformed NMR of⁴⁵Sc in TiO₂, the quadrupole moment of⁴¹Sc has been determined as |Q(⁴¹Sc; 7/2^–)|=166±8 mb.     

Nuclear spin dependence of polarization enhancement by multi-tilted foils studied by short-lived beta-emitters8B and12B

In order to study the basic mechanism of polarization enhancement realized by the multitilted foil technique, nuclear polarization of short-lived beta-emitter⁸B(T_1/2=769 ms,I =2⁺) was induced. Utilizing up to ten tilted foils, the polarization enhancement was measured as a function of the foil numbers. The observed enhancement for⁸B was combined with the previous results for¹²B(I =1⁺,T _1/2=20 ms) which has the same atomic configurations but different nuclear spin. Analyzing these results in the framework of the classical vector model, the essential features of the enhancement depending on the nuclear spin was disclosed.