Synthesis of end‐functionalized poly(phenylacetylene)s with well‐characterized palladium catalysts

End‐functionalized poly(phenylacetylene)s were synthesized by the polymerization of phenylacetylene (PA) using the well‐defined palladium catalysts represented as [(dppf)PdBr(R)] {dppf = 1,1′‐bis(diphenylphosphino)ferrocene}. The Pd catalysts having a series of R groups such as o‐tolyl, mesityl, C(Ph)?CPh₂, C₆H₄‐o‐CH₂OH, C₆H₄‐p‐CN, and C₆H₄‐p‐NO₂ in conjunction with silver triflate polymerized PA to give end‐functionalized poly(PA)s bearing the corresponding R groups in high yields. The results of IR and NMR spectroscopies and MALDI‐TOF mass analyses proved the introduction of these R groups at one end of each polymer chain. The poly(PA) bearing a hydroxy end group was applied as a macroinitiator to the synthesis of a block copolymer composed of poly(PA) and poly(β‐propiolactone) moieties. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Synthesis and light‐emitting properties of carbazole‐based copolymers bearing cyano‐substituted arylenevinylene chromophore

Two arylenevinylene compounds bearing the cyano group at α‐position ( 6 ) and β‐position ( 9 ) from the dialkoxylphenylene unit were synthesized, in which the molecular termini were functionalized with 3‐bromocarbazole. The Suzuki coupling copolymerization of these compounds with 1,4‐bis[(3′‐bromocarbazole‐9′‐yl)methylene]‐2,5‐didecyloxybenzene and 9,9‐dihexylfluorene‐2,7‐bis(boronic acid) was carried out to obtain copolymers ( cp67 and cp97 ) containing the cyano‐substituted arylenevinylene fluorophore of 7 mol %. Model compounds ( 6 ′ and 9 ′) corresponding to the arylenevinylene fluorophore were also prepared. The UV spectra of copolymers resembled that of homopolymer hp with no arylenevinylene segment in both CHCl₃ solution and thin film. The emission maxima of copolymers in CHCl₃ (394 nm) agreed with that of homopolymer indicating that the emission bands originated from the carbazole‐fluorene‐carbazole segment. The emission maximum wavelength of copolymer cp67 in thin film (477 nm) indicated fluorescence from the cyano‐substituted arylenevinylene fluorophore because of the occurrence of fluorescence resonance electron transfer. In contrast, copolymer cp97 showed fluorescence at 528 nm to suggest the formation of a new emissive species such as a charge‐transfer complex (exciplex). © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 91–98, 2010     

Catalytic asymmetric syntheses and biological activities of singly dehydroxylated 19-nor-1alpha,25-dihydroxyvitamin D(3) A-ring analogs in cancer cell differentiation and apoptosis

BACKGROUND: 1alpha,25-Dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) has been shown to modulate not only proliferation and differentiation, but also apoptosis in malignant cells, indicating that it could be useful for treating cancer. Little information is available concerning the structural motifs of the 1alpha, 25(OH)(2)D(3) molecule responsible for modulation of differentiation and apoptosis, however. We set out to synthesize singly dehydroxylated A-ring analogs of 19-nor-1alpha,25(OH)(2)D(3) in a catalytic asymmetric fashion, and to investigate their biological activities in leukemia HL-60 cells. RESULTS: A series of singly dehydroxylated 19-nor-1alpha,25-dihydroxyvitamin D(3) A-ring analogs were synthesized using a combinatiorial sequence of regioselective propiolate-ene reaction and catalytic asymmetric carbonyl-ene cyclization. Surprisingly, the analogs could be clearly divided into two categories; one group, bearing 1alpha-hydroxy or 3beta-hydroxy groups in the A-ring, were potent differentiators and the second group, bearing 1beta-hydroxy or 3alpha-hydroxy groups, were potent stimulators of apoptosis. CONCLUSIONS: We have clearly identified the structural motifs of 19-nor-1alpha,25(OH)(2)D(3) analogs responsible for differentiation and apoptosis in HL-60 cells. These findings will provide useful information not only for development of therapeutic agents for treatment of leukemia and other cancers, but also for structure-function studies of 1alpha,25(OH)(2)D(3).     

Fluorescent modification for peptide sequencing by postsource decay-matrix assisted laser desorption/ionization-mass spectrometry

The sequential analysis of a peptide of CDYEGRLI, relating to the nucleic proteins in influenza virus, was performed by the postsource decay (PSD) fragmentation method using matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). The sequence of the peptide was difficult to analyze by MALDI-MS since the PSD fragment ions of the peptide were almost never observed and were not amenable to complete sequence interpretation. The peptide was modified by 4(5)-(iodoacetamide) fluorescent reagent to improve the sensitivity of the MALDI-PSD fragment spectrum. In the spectrum of the fluorescent modified peptide, almost all sequential b-series fragment ions were observed clearly, which was sufficient for complete sequence interpretation. The results indicate the advantage of fluorescent modification for the total sequencing of the peptides by MALDI-MS.     

1,2-silyl-migrative cyclization of vinylsilanes bearing a hydroxy group: stereoselective synthesis of multisubstituted tetrahydropyrans and tetrahydrofurans(1)

Acid-catalyzed intramolecular addition of a hydroxy group to alpha-alkylated vinylsilanes has been studied. Treatment of (Z)-5-alkyl-5-silyl-4-penten-1-ols 1 (R = alkyl) with 5 mol % TiCl(4) in CHCl(3) gave trans-2-alkyl-3-silyltetrahydropyrans 2 exclusively (trans/cis = >99/1 to 97/3). The cyclization efficiency and rate strongly depended on the geometry of the C-C double bond and the silyl group. The use of (E)-vinylsilanes resulted in lower yields with poor cis-selectivity. In the cyclization of (Z)-1 (R = Bu), the silyl group used, the reaction time, and the yield of 2 were as follows: SiMe(2)Ph, 9.5 h, 75%; SiMe(3), 7.5 h, 66%; SiMePh(2), 24 h, 58%; SiMe(2)-t-Bu, 0.75 h, 85%; SiMe(2)Bn, 1.5 h, 78%. This 1,2-silyl-migrative cyclization could be applied to stereoselective synthesis of trisubstituted tetrahydropyrans. The acid-catalyzed reaction of 1-, 2-, or 3-substituted (Z)-5-silyl-4-nonen-1-ols 8 gave r-2,t-3,c-6-, r-2,t-3,t-5-, or r-2,t-3,c-4-trisubstituted tetrahydropyrans with high diastereoselectivity, respectively. (Z)-4-Alkyl-4-silyl-3-buten-1-ols 5 as well as 1 underwent the 1,2-silyl-migrative cyclization to give 2-alkyl-3-silyltetrahydrofurans 6 with high trans-selectivity. This silicon-directed cyclization was also available for the stereoselective synthesis of tri- and tetrasubstituted tetrahydrofurans.     

On-line measurement of intramolecular carbon isotope distribution of acetic acid by continuous-flow isotope ratio mass spectrometry

Molecular and intramolecular carbon isotope measurements of acetic acid present in natural environments have been performed by off-line procedures. The off-line method is complicated and time-consuming and requires micromolar to millimolar amounts of sample. This limits geochemical isotopic studies, especially at the intramolecular level, on acetic acid present in natural samples. Here, we examine an on-line measurement of intramolecular carbon isotope distribution of acetic acid using continuous-flow isotope ratio mass spectrometry (CF-IRMS) coupled with an on-line pyrolysis system. This is achieved by measurement of the respective carbon isotope ratios of CH4 and CO2 produced by on-line pyrolysis of acetic acid. Results for authentic standards of pure acetic acid demonstrated the practicality of this on-line method, although the carbon isotope ratio of the methyl group could not be determined directly. The precision of the carbon isotope measurements was 0.4 per thousand (1sigma). The carbon isotope distribution determined by the on-line method was identical to that determined by the conventional off-line method within analytical error. The advantages of the on-line method compared with the conventional off-line method are that it is less laborious, requires less analytical time (less than one hour per sample) and, most importantly, uses smaller sample sizes (ca. 10 nanomole). An application of this on-line method to natural geochemical samples will provide an insight into the geochemical cycle of acetic acid.     

Self-organized lipid-porphyrin bilayer membranes in vesicular form: nanostructure,photophysical properties,and dioxygen coordination

An amphiphilic tetraphenylporphyrin and its iron complex bearing four phospholipid substituents, in which a trimethylolethane residue connects the two acyl chains (lipid-porphyrins), have been synthesized. The free-base lipid-porphyrin 6a self-organizes in aqueous media to form spherical unilamellar vesicles with a diameter of 100 nm and a uniform thickness of 10 nm, which corresponds to twice the length of the molecule. In the visible absorption spectrum, the porphyrin Soret band was significantly red-shifted (12 nm) relative to that of the monomer in benzene/MeOH solution due to the excitonic interaction of the porphyrin chromophores. The [symbol: see text]-A isotherm of 6a gave an area per molecule of 2.2 nm2, which allowed the estimation of the number of molecules in a single vesicle (2.3 x 10(4)). Double-layered Langmuir-Blodgett (LB) films of 6a on a glass surface exhibited an absorption spectrum identical to that of the 6a vesicles in bulk aqueous solution, and this suggests that they contain similar geometric arrangements of the porphyrin moieties. Exciton calculations on the basis of our structural model reproduced the bathochromic shift of the Soret band well. In the photophysical properties of the 6a vesicles, the characteristics of J-aggregated porphyrins substantially predominate: strong fluorescence and extremely short triplet lifetime. The iron complex 6b with a small molar excess of 1-dodecylimidazole (DIm) also formed spherical unilamellar vesicles (100 nm phi). Scanning force microscopy after evaporation on a graphite surface revealed 6b/DIm vesicles with a vertical height of 19.8 nm, which coincided with the thickness of the double bilayer membranes. The ferrous 6c formed a bis(DIm)-coordinated low-spin FeII complex under an N2 atmosphere. Upon addition of O2 to this solution, a kinetically stable O2 adduct was formed at 37 degrees C with a half-life of 17 h. Distinct gel-phase (liquid-crystal) transitions of the lipid-porphyrin membranes were clearly observed; the free base 6a displayed a higher transition temperature (56 degrees C) than the iron complex. Magnetic circular dichroism and infrared spectroscopic studies proved that molecular O2 coordinates to the self-organized lipid-porphyrinatoiron(II) vesicles in aqueous media.     

UVB irradiation of normal human skin favors the development of type-2 T-cells in vivo and in primary dermal cell cultures

To determine the effect of UVB exposure on the balance of type-1 or type-2 T-cells in skin, we examined the expression of key markers interferon (IFN)-gamma and interleukin (IL)-4 in cryostat sections. IFN-gamma mRNA was clearly detectable in nonirradiated control skin, and IFN-gamma protein was found in 2% of the dermal CD3pos T-cells, whereas IL-4 mRNA was hardly detectable, and no IL-4 protein was found. In contrast, IL-4 mRNA expression increased upon irradiation, and IL-4 was found in 2% of the T-cells at day 2 after UVB-exposure. Concomitantly, IFN-gamma mRNA expression decreased, and IFN-gamma protein became absent. We also analyzed T-cells present in primary dermal cell cultures, which were used as an in vitro equivalent of the in vivo situation. As compared with T-cells from control skin, T-cells in dermal cell cultures from UVB-exposed skin displayed an increased IL-4 and decreased IFN-gamma expression. No such skewing occurred when the T-cells from irradiated skin were cloned in the absence of a dermal microenvironment. Except for an occasional positive T-cell, type-1-associated cell-surface markers (CCR5, CXCR3) or type-2 markers (CCR3, CD30, CRTH2) were undetectable in situ. But these markers were expressed on cultured dermal T-cells from UVB-exposed and control skin at a comparable level, but did not correlate with the IFN-gamma and IL-4 production. Altogether, UVB-induced changes of the dermal microenvironment favor the development of type-2 T-cells.     

A novel synthesis of substituted quinolines using ring-closing metathesis (RCM): its application to the synthesis of key intermediates for anti-malarial agents

A method for synthesizing substituted quinolines using ruthenium-catalyzed ring-closing metathesis as a key step has been developed. Substituted 1,2-dihydroquinolines, 4-silyloxy-1,2-dihydroquinoline and 4-methoxy-1,2-dihydroquinoline, were successfully synthesized in excellent yields via ene-ene metathesis and silyl or alkyl enol ether-ene metathesis, respectively. The synthetic intermediates of the antimalarial agents quinine, chloroquine, and PPMP-quinine hybrid were efficiently synthesized by this methodology.