The synthesis of pyrazolo[3,4-d]pyridazines. Photochemical cyclization to pyrazolo[3,4-d]pyridazin-4(5H)-ones with subsequent functionalization

The synthesis of 1,3-disubstituted and 1,3,5-trisubstituted 1H-pyrazolo[3,4-d]pyridazin-4(5H)-ones is conveniently performed by photochemical cyclization. Functionalization of the former compounds leading to the formation of 1,4-disubstituted and 1,3,4-trisubstituted 1H-pyrazolo[3,4-d]pyridazines is smoothly effected through pertinent nucleophilic substitutions.     

Tetrakisdehydro[16]annuleno[18]annulene

Tetrakisdehydro[16]annuleno consisting of trisdehydro[16]annulene and bisdehydro[18] annulene has been synthesized. Induction of para- and diamagnetic ring currents in 16- and 18-membered rings, respectively, was clearly recognized by the ¹H NMR spectroscopy. A marked suppresion of the diatropicity in the 18π moiety was observed in the same trend as observed in tetrakisdehydro[14]annuleno[16]annulene.     

Synthesis of poly-3,3-bis(chloromethyl)-oxacyclobutane (penton) derivatives

The derivatives of poly-3,3-bis(chloromethyl)oxacyclobutane were prepared by the reaction of the chloromethyl group with organic alkali salts at 100–130°C. in dimethyl sulfoxide. Various reagents were used, including sodium cyanide, sodium acetate, sodium thiophenolate, sodium phenolate, sodium methoxide, sodium diethyl malonate, and potassium phthalimide. For all the substitution reactions, the infrared spectra and elementary analyses substantiated the structures of the designated products. The intrinsic viscosities of the derivatives decreased with increasing the reaction time. It was found that the ions of these salts are strong nucleophiles in dimethyl sulfoxide.     

Formation of multihollow structures in crosslinked composite polymer particles

Micron-size monodisperse polymer particles having multihollow structures were prepared as follows. First, micron-size monodisperse polystyrene/poly(styrene-divinylbenzene) (PS/P(S-DVB)) composite particles were produced by seeded copolymerization of S and DVB with 2,2-azobisisobutyronitrile as an initiator in the ethanol/water (76/24, weight ratio) medium in the presence of 2.37 m-size monodisperse PS seed particles produced by dispersion polymerization. The molar ratio of S/DVB was changed in the range of 1/110/1. The uncrosslinked polymer within the composite particles was extracted with toluene under reflux. For the highest DVB content (S/DVB=1/1, molar ratio), one large hollow was observed in a part of the composite particles after the extraction. For the middle DVB content (S/DVB=4/1, molar ratio), multihollow structure was observed in all the particles. For the lowest DVB content (S/DVB=10/1, molar ratio), fine multihollow structure was observed in all the particles.Part CXLIII of the series Studies on Suspension and Emulsion     

The competition between fusion-fission and deeply inelastic reactions in the medium mass systems

The competition between fusion-fission and deeply inelastic reactions in the Cl + Ni system has been studied by investigating the exit channelQ-value dependence of theZ-distributions of fission-like fragments. TheZ-, kinetic energy- and angular distributions of the fission-like fragments produced in the³⁷Cl +⁶⁴Ni system atE _lab=170, 186 MeV and in the²⁸Si +⁷⁴Ge system atE _lab=176 MeV have been measured by counter telescopes. TheZ-distribution of the³⁷Cl +⁶⁴Ni system was found to be essentially the same as that of the³⁵Cl +⁶²Ni system at the same bombarding energy. It is shown that this result can not be explained by the statistical fusion fission model but is consistent with a deeply inelastic model. A systematic study of the fission-like phenomenon in this mass region indicates that the maximum angular momenta for fusion reactions as well as the minimum angular momenta for DIC can be reproduced by the Bass model in the sliding limit (f=1.0) while the maximum angular momenta for fully energy-damped deeply inelastic reactions are governed by the strong interaction radius as predicted by the successive critical distance fusion model. The significance of these results are discussed.Communicated by V. Metag     

Short-term frequency stabilization of diode-laser-pumped Nd:YAG lasers using double-pendulum suspended cavities

We describe the improvement of short-term frequency stability of diode-laser-pumped Nd:YAG lasers. To improve the vibrational isolation of reference cavities, the reference cavities were suspended by a double pendulum with magnetic damping. The frequency noise was reduced to lower than 1 Hz/Hz at Fourier frequencies higher than 5 Hz and the minimum noise of 7 × 10^–3 Hz/Hz was recorded. The minimum root Allan variance was about 10^–14 for the sampling time of 0.01 s. Heating of the reference cavity by absorbed laser power caused the thermal drift of cavity resonance frequencies. It resulted in the laser linewidth in the range of 30–50 Hz.     

Probing the effect of the binding site on the electrostatic behavior of a series of carotenoids reconstituted into the light-harvesting 1 complex from purple photosynthetic bacterium Rhodospirillum rubrum detected by stark spectroscopy

Reconstitutions of the LH1 complexes from the purple photosynthetic bacterium Rhodospirillum rubrum S1 were performed with a range of carotenoid molecules having different numbers of C=C conjugated double bonds. Since, as we showed previously, some of the added carotenoids tended to aggregate and then to remain with the reconstituted LH1 complexes (Nakagawa, K.; Suzuki, S.; Fujii, R.; Gardiner, A.T.; Cogdell, R.J.; Nango, M.; Hashimoto, H. Photosynth. Res. 2008, 95, 339-344), a further purification step using a sucrose density gradient centrifugation was introduced to improve purity of the final reconstituted sample. The measured absorption, fluorescence-excitation, and Stark spectra of the LH1 complex reconstituted with spirilloxanthin were identical with those obtained with the native, spirilloxanthin-containing, LH1 complex of Rs. rubrum S1. This shows that the electrostatic environments surrounding the carotenoid and bacteriochlorophyll a (BChl a) molecules in both of these LH1 complexes were essentially the same. In the LH1 complexes reconstituted with either rhodopin or spheroidene, however, the wavelength maximum at the BChl a Qy absorption band was slightly different to that of the native LH1 complexes. These differences in the transition energy of the BChl a Qy absorption band can be explained using the values of the nonlinear optical parameters of this absorption band, i.e., the polarizability change Tr(Deltaalpha) and the static dipole-moment change |Deltamu| upon photoexcitation, as determined using Stark spectroscopy. The local electric field around the BChl a in the native LH1 complex (ES) was determined to be approximately 3.0x10(6) V/cm. Furthermore, on the basis of the values of the nonlinear optical parameters of the carotenoids in the reconstituted LH1 complexes, it is possible to suggest that the conformations of carotenoids, anhydrorhodovibrin and spheroidene, in the LH1 complex were similar to that of rhodopin glucoside in crystal structure of the LH2 complex from Rhodopseudomonas acidophila 10050.     

Profiling of N- and O-glycopeptides of erythropoietin by capillary zwitterionic type of hydrophilic interaction chromatography/electrospray ionization mass spectrometry

Capillary zwitterionic-type hydrophilic interaction chromatography (ZIC-HILIC)/ESI-MS has been applied to the Glu-C digest of recombinant human erythropoietin (rhEPO) expressed in Chinese hamster ovary (CHO) cells. N-Glycopeptides (105) and O-glycopeptides (8) were detected in a single run of the capillary ZIC-HILIC/ESI-MS analysis. Among them, N-acetyl-neuraminic acids (Neu5Ac) of N- and O-glycans were partially acetylated and some were replaced with N-glycoyl-neuraminic acid (Neu5Gc). Their retentions in the ZIC-HILIC separation can be explained to some extent with the degree of acetylation and N-glycoylation, both of which influence the hydrophilicity/hydrophobicity of the N- and O-glycan moieties of glycopeptides.     

Chromatographic deuterium isotope effects of derivatized N-glycans and N-glycopeptides in a zwitterionic type of hydrophilic interaction chromatography

HPLC/MS is now an essential method for the analysis of glycans and glycopeptides. A technique using ICATs is also becoming popular for their comparative/quantitative analysis based on MS signal intensities. However, the RP HPLC most often used causes "doublet" peaks of deuterium-labeled and nonlabeled peptides, which are well known for causing the chromatographic deuterium isotope effect. Such doublet peaks are undesirable for precise comparison of MS signal intensities. This report shows that, in the zwitterionic type of hydrophilic interaction chromatography, the chromatographic deuterium isotope effect is negligibly small for N-glycans derivatized with deuterium-labeled 2-aminopyridine and N-glycopeptides derivatized with deuterium-labeled succinic anhydride.     

High-throughput sorting of nanoliter droplets enabled by a sequentially addressable dielectrophoretic array

Droplet microfluidics has emerged as a powerful tool for a diverse range of biomedical and industrial applications such as single-cell analysis, directed evolution, and metabolic engineering. In these applications, droplet sorting has been effective for isolating small droplets encapsulating molecules, cells, or crystals of interest. Recently, there is an increased interest in extending the applicability of droplet sorting to larger droplets to utilize their size advantage. However, sorting throughputs of large droplets have been limited, hampering their wide adoption. Here, we report our demonstration of high-throughput fluorescence-activated droplet sorting of 1 nL droplets using an upgraded version of the sequentially addressable dielectrophoretic array (SADA), which we reported previously. The SADA is an array of electrodes that are individually and sequentially activated/deactivated according to the speed and position of a droplet passing nearby the array. We upgraded the SADA by increasing the number of driving electrodes constituting the SADA and incorporating a slanted microchannel. By using a ten-electrode SADA with the slanted microchannel, we achieved fluorescence-activated droplet sorting of 1 nL droplets at a record high throughput of 1752 droplets/s, twice as high as the previously reported maximum sorting throughput of 1 nL droplets.