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Delamanid has been studied extensively and approved for the treatment of pulmonary multidrug-resistant tuberculosis; however, its potential in the treatment of extrapulmonary tuberculosis remains unknown. We previously reported that, in rats, delamanid was broadly distributed to various tissues in addition to the lungs. In this study, we simulated human plasma concentration-time courses (pharmacokinetic profile) of delamanid, which has a unique property of metabolism by albumin, using two different approaches (steady-state concentration of plasma-mean residence time [C(ss)-MRT] and physiologically based pharmacokinetic [PBPK] modeling). In C(ss)-MRT, allometric scaling predicted the distribution volume at steady state based on data from mice, rats, and dogs. Total clearance was predicted by in vitro-in vivo extrapolation using a scaled albumin amount. A simulated human pharmacokinetic profile using a combination of human-predicted C(ss) and MRT was almost identical to the observed profile after single oral administration, which suggests that the pharmacokinetic profile of delamanid could be predicted by allometric scaling from these animals and metabolic capacity in vitro. The PBPK model was constructed on the assumption that delamanid was metabolized by albumin in circulating plasma and tissues, to which the simulated pharmacokinetic profile was consistent. Moreover, the PBPK modeling approach demonstrated that the simulated concentrations of delamanid at steady state in the lung, brain, liver, and heart were higher than the in vivo effective concentration for Mycobacterium tuberculosis. These results indicate that delamanid may achieve similar concentrations in various organs to that of the lung and may have the potential to treat extrapulmonary tuberculosis. more...

Brexpiprazole, a serotonin-dopamine activity modulator, is indicated for the treatment of schizophrenia and also adjunctive therapy to antidepressants for the treatment of Major Depressive Disorder. To determine the drug–drug interaction risk for cytochrome P450, and SLC and ABC transporters, brexpiprazole and its metabolite, DM-3411 were assessed in this in vitro investigation.Brexpiprazole exhibited weak inhibitory effects (IC50 >13 μmol/L) on CYP2C9, CYP2C19, CYP2D6 and CYP3A4 activities, but had moderate inhibitor activity on CYP2B6 (IC50 8.19 μmol/L). The ratio of systemic unbound concentration (3.8 nmol/L) to the Ki value was sufficiently low. DM-3411 had comparable inhibitory potentials with brexpiprazole only for CYP2D6 and CYP3A4. The mRNA expressions of CYP1A2, CYP2B6 and CYP3A4 were not changed by the exposure of brexpiprazole to human hepatocytes.Brexpiprazole and DM-3411 exhibited weak or no inhibitory effects for hepatic and renal transporters (OATPs, OATs, OCTs, MATE1, and BSEP), except for MATE-2K (0.156 μmol/L of DM-3411), even for which the ratio to systemic unbound concentration (5.3 nmol/L) was sufficiently low.Brexpiprazole effected the functions of P-gp and BCRP with IC50 values of 6.31 and 1.16 μmol/L, respectively, however, the pharmacokinetic alteration was not observed in the clinical concomitant study on P-gp and BCRP substrates.These in vitro data suggest that brexpiprazole is unlikely to cause clinically relevant drug interactions resulting from the effects on CYPs or transporters mediating the absorption, metabolism, and/or disposition of co-administered drugs. Brexpiprazole, a serotonin-dopamine activity modulator, is indicated for the treatment of schizophrenia and also adjunctive therapy to antidepressants for the treatment of Major Depressive Disorder. To determine the drug–drug interaction risk for cytochrome P450, and SLC and ABC transporters, brexpiprazole and its metabolite, DM-3411 were assessed in this in vitro investigation. Brexpiprazole exhibited weak inhibitory effects (IC50 >13 μmol/L) on CYP2C9, CYP2C19, CYP2D6 and CYP3A4 activities, but had moderate inhibitor activity on CYP2B6 (IC50 8.19 μmol/L). The ratio of systemic unbound concentration (3.8 nmol/L) to the Ki value was sufficiently low. DM-3411 had comparable inhibitory potentials with brexpiprazole only for CYP2D6 and CYP3A4. The mRNA expressions of CYP1A2, CYP2B6 and CYP3A4 were not changed by the exposure of brexpiprazole to human hepatocytes. Brexpiprazole and DM-3411 exhibited weak or no inhibitory effects for hepatic and renal transporters (OATPs, OATs, OCTs, MATE1, and BSEP), except for MATE-2K (0.156 μmol/L of DM-3411), even for which the ratio to systemic unbound concentration (5.3 nmol/L) was sufficiently low. Brexpiprazole effected the functions of P-gp and BCRP with IC50 values of 6.31 and 1.16 μmol/L, respectively, however, the pharmacokinetic alteration was not observed in the clinical concomitant study on P-gp and BCRP substrates. These in vitro data suggest that brexpiprazole is unlikely to cause clinically relevant drug interactions resulting from the effects on CYPs or transporters mediating the absorption, metabolism, and/or disposition of co-administered drugs. more...

We constructed machine learning-based pharmacokinetic prediction models with very high performance. The models were trained on 26138 and 16613 compounds involved in metabolic stability and cytochrome P450 inhibition, respectively. Because the compound features largely differed between the publicly available and in-house compounds, the models learned on the public data could not predict the in-house compounds, suggesting that outside of a certain applicability domain (AD), the prediction results are unreliable and can mislead the design of novel compounds. To exclude the uncertain prediction results, we constructed another machine learning model that determines whether the newly designed compound is inside or outside the AD. The AD was evaluated multi-dimensionally with some explanatory variables: The structural similarities and the probability obtained from the pharmacokinetic prediction model. The accuracy of predicting metabolic stability was 79.9% on the test set, increasing significantly to 93.6% after excluding the low-reliability compounds. The model properly classified the reliability of the compounds. After learning on the in-house compounds, the reliability model classified almost all (90%) of the public compounds as low reliability, indicating that the AD was properly determined by the model. more...

The objective of this study was to obtain the indicators of physicochemical parameters and structurally active sites to design new chemical entities with desirable pharmacokinetic profiles by investigating the process by which machine learning prediction models arrive at their decisions, which are called explainable artificial intelligence. First, we developed the prediction models for metabolic stability, CYP inhibition, and P-gp and BCRP substrate recognition using 265 physicochemical parameters for designing the molecular structures. Four important parameters, including the well-known indicator h_logD, are common in some in vitro studies; as such, these can be used to optimize compounds simultaneously to address multiple pharmacokinetic concerns. Next, we developed machine learning models that had been programmed to show structurally active sites. Many types of machine learning models were developed using the results of in vitro metabolic stability study of around 30000 in-house compounds. The metabolic sites of in-house compounds predicted using some prediction models matched experimentally identified metabolically active sites, with a ratio of number of metabolic sites (predicted/actual) of over 90%. These models can be applied to several screening projects. These two approaches can be employed for obtaining lead compounds with desirable pharmacokinetic profiles efficiently. more...

Recent studies have shown that rebamipide, which suppresses reactive oxygen species, prevents chemoradiotherapy-induced oral mucositis in patients with head and neck cancers. However, anticancer action of radiotherapy and chemotherapy is believed to be partially associated with generation of reactive oxygen species. The aim of this study was to determine whether rebamipide interferes with the antitumor action of radiotherapy and chemotherapy. The effect of rebamipide on tumor cell growth was investigated using a human oral squamous carcinoma cell line, HSC-2, in vitro and in vivo. Rebamipide showed no significant effect on cell or tumor growth in HSC-2 tumor-bearing nude mice. Influences of rebamipide on the antitumor action of radiotherapy and of chemotherapy with cisplatin or docetaxel were investigated using the same animal model. In radiotherapy, the tumor was treated with 2.5 Gy of X-rays for 5 days, and rebamipide (300 mg/kg p.o.) was administered during irradiation periods. In chemotherapy, tumor-bearing mice were treated once with cisplatin (8 mg/kg, i.v.) or docetaxel (15 mg/kg i.v.) and rebamipide (300 mg/kg p.o.) was administered for 5 days following the antitumor drug treatment. Rebamipide did not interfere with the antitumor action of radiotherapy and chemotherapy. more...

Delamanid (Deltyba, OPC-67683) is the first approved drug in a novel class of nitro-dihydro-imidazooxazoles developed for the treatment of multidrug-resistant tuberculosis. Patients with tuberculosis require treatment with multiple drugs, several of which have known drug-drug interactions. Transporters regulate drug absorption, distribution, and excretion; therefore, the inhibition of transport by one agent may alter the pharmacokinetics of another, leading to unexpected adverse events. Therefore, it is important to understand how delamanid affects transport activity. In the present study, the potencies of delamanid and its main metabolites as the substrates and inhibitors of various transporters were evaluated in vitro . Delamanid was not transported by the efflux ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp; MDR1/ABCB1) and breast cancer resistance protein (BCRP/ABCG2), solute carrier (SLC) transporters, organic anion-transporting polypeptides, or organic cation transporter 1. Similarly, metabolite 1 (M1) was not a substrate for any of these transporters except P-gp. Delamanid showed no inhibitory effect on ABC transporters MDR1, BCRP, and bile salt export pump (BSEP; ABCB11), SLC transporters, or organic anion transporters. M1 and M2 inhibited P-gp- and BCRP-mediated transport but did so only at the 50% inhibitory concentrations (M1, 4.65 and 5.71 μmol/liter, respectively; M2, 7.80 and 6.02 μmol/liter, respectively), well above the corresponding maximum concentration in plasma values observed following the administration of multiple doses in clinical trials. M3 and M4 did not affect the activities of any of the transporters tested. These in vitro data suggest that delamanid is unlikely to have clinically relevant interactions with drugs for which absorption and disposition are mediated by this group of transporters. more...

We demonstrated that oligo(9,9-diarylfluorene) derivatives have high potential for optoelectronic applications such as organic lasers and light-emitting organic field-effect transistors (LE-OFETs). The oligo(9,9-diarylfluorene) derivatives have high photoluminescence quantum efficiencies up to ΦPL ≈ 70−75% and very low amplified spontaneous emission thresholds (Eth) down to 0.5 μJ/cm2 in their vacuum-deposited neat films. In particular, the trimer derivatives (B3 and T3) show higher ΦPL and lower Eth than those of the dimers (B2 and T2). Efficient deep-blue LE-OFETs with the electroluminescence (EL) peaking at λpeak = 429 nm were demonstrated using the ter(9,9-diarylfluorene) as the active layer. Rather high luminance up to L ≈ 150 cd/m2 and EL quantum efficiency up to ηext ≈ 0.60% were achieved with the optimum source-drain channel length, indicating bipolar carrier injection in the terfluorene layer under the FET operation. more...

筆者らは, 青色リン光材料をゲスト分子として用いた有機EL素子において, 高効率青色発光を得るためにπ共役系の短いシロキサン化合物であるHexaphenylcyclotri siloxane (DPSiO3) をホスト材料として試みた. この材料をEPA溶液に溶解し, T=77Kにおいてリン光スペクトルを測定したところ, DPSiO3のリン光スペクトルはベンゼンのリン光スペクトルとほぼ同じ波長領域 (λonset～350nm) に観測され, これらの化合物は本質的にベンゼン環にπ電子系が局在していることが示唆された. Iridium (III) bis (4,6-di-fluorophenyl) -pyridinato-N, C2) picolinate (FIrpic) をゲスト分子としたEL素子において, DPSiO3をホストとした素子では最大ηext=11.1%の外部EL量子効率を得ることができた. more...

We fabricated an organic light-emitting field effect transistors (OLEFET) using a co-deposited layer of TPTPT and NTCDA which has p-type and n-type semiconducting behaviors, respectively. The organic layer was formed on a comb type electrode (source-drain electrodes) with a channel length of 25μm on a p-Si/SiO2 substrate. Bipolar and EL characteristics were investigated by changing co-deposition ratio of TPTPT and NTCDA. In the optimum deposition ratio, we observed typical ambipolar characteristics, demonstrating saturation current characteristics at low Vd (source-drain voltage), followed by divergent current characteristics at high Vd. more...

The phosphorescence intensities of the green phosphor, fac tris(2-phenylpyridine) iridium [Ir(ppy)3], in a polymethylmethacrylate [PMMA] host matrix are independent of temperature, while the phosphorescence lifetimes increase significantly at temperatures below T ∼ 50 K. In this paper, to rationalize the characteristic temperature dependence of the transient phosphorescence of Ir(ppy33, we propose a model where the triplet excited states split by spin-orbital interaction, forming three levels in which mutual energy transfer between the sub-levels of triplet states occurs. We discuss the validity of this numerical model by comparing with the experimental result of the transient phosphorescence in a PMMA host matrix and demonstrate that the model well explains the characteristic temperature dependence. more...

Summary: Grepafloxacin (GPFX) is a new quinolone antibiotic (NQ) which is highly distributed to the lung and other tissues. In the present study, to characterize the distribution mechanism of GPFX to the lung, the uptake of GPFX by isolated rat lung cells was examined in vitro. GPFX was rapidly taken up by the cells, and the uptake reached a steady-state within 5 min. The cell-to-medium concentration ratio at equilibrium was 56.8 ± 1.9 μ L/mg protein, which was much higher than the cellular volume. GPFX uptake consisted of a saturable component (K m : 264 ± 181 μ M, V max : 2.94 ± 2.33 nmol/min/mg protein) and a nonsaturable component (P dif : 7.04±2.17 μ L/min/mg protein). The uptake of GPFX was reduced in the presence of ATP-depletors (FCCP and Rotenone) and by the replacement of sodium with choline in the medium, suggesting that GPFX uptake is at least partially mediated by an Na + - and energy-dependent process. GPFX uptake tended to be reduced in the presence of other NQs such as levofloxacin, lomefloxacin and sparfloxacin, but was only minimally affected by the substrates of several uptake mechanisms already identified in the liver and kidney such as taurocholate, p-aminohippurate, L-carni- tine and tetraethylammonium. These results suggested that GPFX is taken up by the lung partially via carrier-mediated transport system(s), distinct from the identified transporters, and such active transport systems may at least partially account for the efficient distribution of GPFX to the lung. more...

To realize an efficient electron injection electrode into organic layers by photolithography, we form a MgAu alloy electrode which has capability of low work function and high durability for humidity and organic solvents during photolithography process. The MgAu alloy thin film shows a work function of 3.7eV which is comparable with that of a neat Mg layer and 0.8eV lower than that of a neat Au layer. The low work function of 3.7eV was maintained even after the photolithography process, suggesting excellent stability for the solvent treatments. We examine a MgAu alloy comb bottom electrode for organic field-effect transistor (OFET) and successfully obtain FET operation of n-type driving. We also demonstrate efficient electron injection characteristics of a MgAu alloy cathode in organic light-emitting diodes (OLEDs). The MgAu alloy cathode can inject electrons efficiently similar to the conventional MgAg cathode. more...

High efficiency white organic light emitting diodes (WOLED) have been expected for applications of lighting, illumination and back-light sources for LCD. Recently, since organic phosphors demonstrated very high electroluminescence (EL) quantum efficiency of ˜100%, high efficiency WOLED with the organic phosphors has been anticipated. In this study, we employed an emitter layer which is doped with blue and red phosphorescence molecules. In our optimized device structure, we obtained maximum EL quantum efficiency of 4%. However, the shapes of the EL spectrum were strongly dependent on current density. With analysis of exciton decay process under optical and electrical excitations, we conclude that triplet-triplet annihilation occurs in blue and red phosphors independently, resulted in a significant change of the EL spectrum. Thus, the coincidence of the lifetimes of the blue and red phosphors is indispensable to escape change of EL spectrum with current density. more...

We demonstrate high-efficiency white electrophosphorescence in organic light emitting diodes (OLED) employing blue and red phosphorescent molecules. As an emitting layer, bis[2-(4,6-difluorophenyl)pyridinato- N,C2’] iridium picolinate (FIrpic) as blue and bis[2-(2’-benzo[4,5-a]thienyl)pyridinato-N,C3’]iridium (acetylacetonate) [Btp2Ir(acac)] as red phosphors were doped into a 4,4’-bis(9-carbazolyl)-2,2’-biphenyl (CBP) host. The OLED characteristics using multi-phosphors doped layers were studied. We focused on suppression of the color change with an increase of a current density while keeping high-efficiency. With an insertion of a 3 nm-thick 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP) layer, high ηext of 4.9±0.5% and pure white emission of CIE (0.32, 0.33) at 10 mA/cm2 were achieved. Moreover, the color change with an increase of a current density was suppressed to a certain extent with in an insertion of other buffer layers, CBP and bis[N-(1-naphthyl)-N-phenyl]benzidine (α-NPD). more...

Femtosecond time-resolved fluorescence spectroscopy has been used to study the excited-state dynamics of pharaonis phoborhodopsin (ppR) from Natronobacterium pharaonis. Upon excitation of ppR with ... more...

We present a new analytical method of molecular orientation in films using a phase measurement of second harmonic generation (SHG) with a theoretical curve fitting. The new analytical method provides the average direction of molecules and the absolute value of the effective second-order nonlinear optical constant (|d eff|) simultaneously. In conventional methods, the average direction of molecules in a sample has been relatively determined with that in a standard sample having preknown molecular direction. The second harmonic (SH) interference fringe obtained between a reference having preknown molecular direction and the sample has been compared with that between the reference and the standard sample. In the new method, however, the average direction of molecules can be obtained without the standard sample. The value of |d eff| is calculated through the fitting process, the average direction of molecules is determined by the sign or the phase of d eff, which is introduced by a reference. Complete express... more...

Dewetting-induced crystallization from hot trichlorobenzene solutions led to the formation of aligned pentacene microfibers or plates, depending on preparation conditions. Fibers with a length of several hundred micrometer and a width of less than one micrometer can be prepared. Bottom-contact field effect transistors with fibers that were oriented perpendicular to the source and drain electrodes showed carrier mobilities as high as 0.04 cm2/Vs. In comparison, plate-like pentacene gave corrected mobilities of up to 0.2 cm2/Vs. [DOI: 10.1380/ejssnt.2009.568] more...

A scanning near-field optical microscope (SNOM) combined with a scanning tunneling microscope (STM) is used to investigate nanoscopic optical phenomena both in the near-field region and in the proximity. The system is realized by introducing a doubly metal-coated optical fiber tip with an extremely small aperture, on which metal-coating is performed to obtain a half-transparent conducting tip. A simultaneous SNOM/STM observation is performed for an Au (111) surface, where the evanescent field standing on the tip vicinity through the aperture is scattered by the local structures of the sample and the far-field component of the scattered light is collected as an optical signal. The distance con-trol is carried out under constant current condition in order to separate the optical properties from surface topography. λ/100 optical resolution and the identical channel transport both for electrons and photons are achieved. more...

For tetraphenylporphyrin derivatives substituted with four fluorocarbon chains (TFPP), monolayers on the water surface were studied with the Brewster angle microscope together with pressure-area curves. It was found that heterogeneous aggregated structures of the monolayers were dependent upon the chain length of fluorocarbons, the metal-free or Mn-TFPP, and the periods after spreading. Polarized UV-visible spectra for the monolayer assemblies indicated that the porphyrin rings in the films were tilted on the average, but had a tendency to adopt an orientation more parallel to the water surface as the chain length of the fluorocarbon increased. The third-order nonlinear optical susceptibility for the monolayer assembly of TFPP with the shorter chains was found to be 7.0 x 10(-13) esu, and those of Mn-TFPP were enlarged. Copyright 1998 Academic Press. more...

We have used multilamellar crystals of the ATP-driven calcium pump from sarcoplasmic reticulum to address the structural effects of calcium binding to the enzyme. They are stacks of disk-shaped two-dimensional crystals. A density map projected along the lipid bilayer was obtained at 9-Å resolution by frozen-hydrated electron microscopy. Although only in projection, much more details of the structure were revealed than previously available, especially in the transmembrane region. Quantitative comparison was made with the model obtained from the tubular crystals of this enzyme formed in the absence of calcium. Unexpectedly large differences in conformation were found, particularly in the cytoplasmic domain. more...

We have developed an ab initio method for predicting the tertiary structures of globular proteins on the basis of the mechanisms of protein folding. This method is referred to as the `island model'. The term island implies a local structure yielded during folding such as secondary structure. Several islands pack into bigger ones step by step and then they reach a compact tertiary structure. The driving force of packing is hydrophobic interaction which brings hydrophobic residues closer through its long-range nature and the specificity of residue pairing after secondary-structure formation. The island model is applicable to any type of proteins irrespective of sequential homology, since the island model is simply based on physicochemical mechanisms of folding. The folding simulation based on the island model is reviewed by illustrating the results for representative globular proteins such as cytochrome b562, sea hare myoglobin and BPTI. These results indicate that the island model can elucidate the folding mechanism and predict the tertiary structures of proteins. more...

Main-Chain Polymers with Nonlinear Optical Chromophores as a Slipped Shoulder-to-Shoulder Arrangement

Domains consisting of J aggregates in a single monolayer deposited on a silica substrate were probed by scanning near-field optical microscopy. Since the fluorescence intensity changes smoothly from the center to the edge of a domain, it is likely that the J aggregates are homogeneously distributed in each domain of the monolayer. more...

We have developed a novel multifunctional chromophore for photorefractive applications. This chromophore, a carbazole oligomer, possesses all the properties required for photorefractivity. Furthermore, because of its good film forming properties, it can be used for optical image processing. The photocarrier generation properties of this chromophore and its second-order nonlinear optical response in acceptor-substituted carbazoles were examined by xerographic discharge, second-harmonic generation, and electro-optic measurements. Photorefractivity was measured directly by two-beam coupling and four-wave mixing experiments. more...

Membrane vesicles of wild-type Halobacterium sp. mex strain show a wavy absorbance change which has not been so far reported in halophilic archaebacteria. A white mutant strain lacking carotenoids did not show the wavy absorbance change. The wavy absorbance change in the range of 440–590 nm was induced by a red flash (600–640 nm), which photoexcited electrogenic ion pumps, mex bacteriorhodopsin and mex halorhodopsin but not carotenoids. The wavy change was also caused by K + diffusion potentials without light. These results suggest that the wavy absorbance change in the membrane vesicles is the voltage-dependent absorbance change of the the carotenoids. more...

Molecules with weak ground-state absorption that form strongly absorbing excited states can be used in optical limiters, which can protect sensors or human eyes from optical damage. Phthalocyanine complexes bearing heavy atoms or paramagnetic groups or in solvents containing heavy atoms show optical limiting enhanced by excited triplet-state absorption. A nonhomogeneous distribution of indium tetra(tert-butyl)phthalocyanine chloride along the beam path substantially enhances the excited-state absorption, yielding an optical limiter with a linear transmittance of 0.70 that can attenuate 8-nanosecond, 532-nanometer laser pulses by factors of up to 540. more...

Concepts and approaches toward the organic photonics research project pursued in our laboratory have been reviewed. Modification of electronic states in one dimensional conjugated polymers enables the creation of a quantum well structure. Carbazole containing oligomers and/or polymers show effective photorefractive effects applicable for image processing. A new technique to distinguish electronic and thermal nonlinearities has been demonstrated. more...

Volume 60, no. 6, p. [3497–3508][1], 2016. Page 3507, left column, lines 2 and 3: “nonnucleoside reverse transcriptase inhibitors (e.g., zidovudine)” should read “nucleoside reverse transcriptase inhibitors (e.g., zidovudine).” [1]: /lookup/doi/10.1128/AAC.03049-15 more...

We demonstrate the operation of an organic switching device using a uniform poly-crystalline Cu:7, 7, 8, 8-Tetracyanoquinodimethane (TCNQ) charge transfer (CT)-complex thin film that is prepared by vacuum vapor codeposition. Characteristic CT-absorption at λ=600-1200 nm was observed in the complex film in the UV-visible spectrum and the cyano stretching peak in the IR spectrum shifted to a higher (more than 29 cm-1) wave number than that of a pristine TCNQ film, suggesting the formation of a CT-complex in the evaporated thin film. Reproducible electrical switching characteristics were observed in the indium tin oxide/Al/(Al2O3)/Cu:TCNQ/Al structure. The device exhibited a clear threshold from low impedance to high impedance at an applied voltage of 10.0±2.0 V and a reverse phenomenon at a negative bias of -9.5±2.0 V. In this study, we demonstrate that a thin Al2O3 layer between the aluminum (Al) anode and Cu:TCNQ layers creates reproducible switching. more...

A two-dimensional (2D) crystal of streptavidin has been obtained by a nonspecific binding method. The protein molecules were bound and formed a dense packing on the film of poly(1-benzyl-L-histidine) spread at the surface of protein solution. The surface film was moderately heated to stimulate crystallization of bound streptavidin. A potential of this method for obtaining 2D crystals of soluble proteins is demonstrated. The present 2D crystal structure of streptavidin resembles that previously obtained by specific binding to biotinylated lipid. We show in addition that the 2D array of protein with usual size approximately 50 A can be imaged using a high resolution scanning electron microscope (HR-SEM) and subject to structural analysis at low resolution. Various limitations in HR-SEM degrade considerably the image quality. However, the usability of a bulk plate as specimen support would make HR-SEM a convenient tool, when such a substrate must be considered in application of protein arrays, and if an intrinsic low resolution is acceptable. more...

Novel carbazole diol monomer with an electron acceptor group for nonlinear optics has been synthesized from 9-(4-hydroxybutyl)-3-formylcarbazole and bis(cyanoacetates). This monomer coploymerized with diisocyanate to give a new series of accordion polymers which contain carbazole moiety in a polymer main chain and hydrogen bonding between the polymer main chains. The polymers were obtained with molecular weights in the range of 6000-11000 and glass transition temperature (Tg) of 69°C-122°C. Films of these polymers were easily made on glass sabstrates by spin coating from chloroform solution. These polymer films can be poled at above Tg. The poled main-chain polymers indicate electric-field- induced alignment of carbazole moieties and second-order nonlinear optical responses. more...

Individual water-soluble molecules of the protein ferritin have been imaged on a silicon surface in pure water at room temperature with the atomic force microscope (AFM). The ferritin molecules formed an ordered monolayer by binding to a charged polypeptide monolayer of poly-1-benzyl-L-histidine (PBLH) spread at the air-water interface. The film, fully wetted with water, was horizontally transferred onto an alkylated silicon wafer for AFM imagings. The hexagonal arrangement of ferritin molecules was imaged with high reproducibility on the whole surface of the film, since the forces between cantilever and the sample could be kept sufficiently smaller than 10(-10) N, mainly due to a "self-screening effect" of the surface charges of the ferritin-PBLH layer. This is the first observation of two-dimensional ordered arrays of water-soluble protein molecules directly confirmed by AFM with molecular resolution. more...

A new halorhodopsin-like pigment from the new halobacterial strain mex (Otomo, J., Tomoika, H. and Sasabe, H. (1992) J. Gen. Microbiol. 138, 1027-1037) was partially purified, and its amino acid sequence from helices A to G was determined using PCR technique. Two arginine residues in the A-B interhelix loop segment, a series of six amino acid residues (EMPAGH) in the B-C interhelix segment and most of the residues near the Schiff base of the retinal were found to be conserved in three halorhodopsins (halobium, pharaonis and mex). This result strongly suggests that these residues are essential for anion pumping function in halorhodopsin. The light-induced ion-pump measurements have shown that the selectivity of anion transport between chloride and nitrate in mex halorhodopsin is lower than that of halobium halorhodopsin, but higher than that of pharaonis halorhodopsin. The number of amino acid residues in the B-C interhelix loop segments is different in each halorhodopsin, and it correlates with their anion (chloride and nitrate) selectivity. These results suggest that the length of the B-C segment affects the selectivity of anion transport in halorhodopsin. more...

SUMMARY: Several new halobacterial strains were isolated from crude solar salts commercially produced in Mexico and Australia. The presence of bacteriorhodopsin (BR)- and halorhodopsin (HR)-like pigment in their total membrane fraction was measured by flash spectroscopy and light-induced ion pumping activity. Two of these strains contained both BR- and HR-like pigments; the others contained only BR-like pigment. DNA hybridization analysis with probes from bacterioopsin and haloopsin genes revealed that the genes encoding the BR- and HR-like pigments were not homologous to those found in Halobacterium halobium R1. In addition, the presence of sensory rhodopsin (SR)- and phoborhodopsin (PR)-like pigment in these membranes was detected by flash spectroscopy. The kinetics of the cyclic photoreaction of the SR-like pigment was more than 15 times slower than that of H. halobium. A PR-like pigment existed in two strains, and the kinetics of the cyclic photoreaction of the PR-like pigment was similar to that found in H. halobium. more...

空気/水の界面に合成ポリペプチドの1種であるポリベンジルヒスチジンの単分子膜を展開し, 吸着を利用してフェリチンおよびカタラーゼの2次元結晶を作成した。これらを疎水処理したシリコンウエハに移し取り, 高分解能SEMを用いて観察した。バルク基板表面におけるタンパク質配列の解析にSEMが有効であることを示した。

Extremely halophilic archaebacterium Halobacterium halobium cells show phototaxis to visible hight. The phototaxis requires vitamine A aldehyde, a retinal. Protein pigments containing retinal are the photoreceptors of the phototaxis. Phoborhodopsin (pR) is a photoreceptor of the negative phototaxis. Sensory rhodopsin (sR) is a photoreceptor of the positive phototaxis and S373, a transient photoproduct of sR, is another photoreceptor of the negative phototaxis. These photoreceptors are too unstable to isolate. Haloalkalophilic archaebacterium Natronobacterium pharaonis cells have pharaonis phoborhodopsin (ppR), which is also a photoreceptor of a negative phototaxis. PPR is solubilized and isolated in an active state, A methylation/demethylation system is involved in the signalling chain from photoreceptor to flagellar motor switch. more...

The preparation method of horizontal transfer onto hydrophobic carbon substrates was used to investigate pure dipalmitoyl phosphatidylcholine (DPPC) monolayers at various surface pressures by high contrast dark field electron microscopy. A microporous structure of a continuous monolayer containing lipid free regions of about 0.1 ∼ 2 μm in diameter was found. The lipid-free regions on the substrate, which decrease in size with growing surface pressure, are related to parts of the phospholipid monolayer in the liquid phase at the air/water interface. The pressure dependence of the density of these liquid phase regions is described by a simple two-phase model for the pressure range from the liquid-expanded/liquid-condensed (LE/LC) phase transition up to high pressures. For evaluating the horizontal transfer properties, DPPC monolayers containing ∼ 1 mol% fluorescent dye molecules were investigated in the same way and by fluorescence microscopy. The structure of these mixed monolayers consisted of small solid phase domains with diameters of about 0.02 ∼ 5 μm arranged in periodic patterns at a submicroscopic scale in a way similar to that known from fluorescence observations (1, 2, 4). Evidence is provided that different contents of impurities may be responsible for the formation of the observed structures of the pure and mixed system. In addition, from high magnification dark field electron micrographs the submicrometer sizes of solid phase domains in DPPC monolayers were estimated for the first time. more...

Fragments of purple membrane were spread at the air/water interface. The interfacial films were transferred onto a silicon wafer with time and initial coverage taken as parameters. The structure of the transferred films was examined with a scanning electron microscope. It was shown that both the size and the packing density of the membrane fragments decreased rapidly with time when the initial coverage was low, and that the intermembrane region was occupied by some substances. An assay by SDS polyacrylamide gel electrophoresis of a built-up film showed that bacteriorhodopsin molecules existed also in the intermembrane region. These results indicated that the denaturation of the purple membrane or the unfolding of bacteriorhodopsin occurred from the periphery of a membrane fragment at the air/water interface. more...

The nonlinear optical properties of poly(1,9-decadiyne) (PDD), which has a diacetylene group in the main chain, were investigated. Using as-prepared films of PDD, no third harmonic generation (THG) was observed. However, after thermal treatment of PDD films, THG appeared and the third order susceptibility, χ(3), was determined to be 1.2×10−12 esu. These heat-treated films were very clear and had no absorption between 600 and 2500 nm. A slab waveguide of polymer thin film was formed on a quartz substrate and its light propagation properties was investigated. more...

The chemical structure, density, and deposition rate of hexamethyldisilazane plasma polymer were investigated in terms of reaction conditions, such as discharge power (W) and mass flow rate (Fm). The importance of the specific energy per mass (W/Fm) as the major controlling parameter of plasma polymerization was confirmed in this study. A notable infiuence of W/Fm on the chemical structure corresponded with the changes in density and deposition yield of plasma polymer. Deposition rate equation was proposed from the simplified model of plasma polymerization. Regression analysis of the experimental data supported the equation. more...

最近5ケ年にわたるLB膜研究の流れを, 電子機能, 光機能及び生体機能の面から眺めた。それぞれの分野で導電性, 非線形光学, タンパク機能などの新しい応用分野が着実に拓かれつつある。

The understanding of the cell signaling pathways and the molecular events leading to cell death of cancer cells will provide in-depth perspective into the identification and development of potent anticancer agents. A balance between cell proliferation and cell death has been raised as a rational target for the management of malignant tumors. In the present study, the authors demonstrated that chemically synthesized sugar-cholestanols consisting of GlcNAcbeta-, Galbeta- and GlcNAcbeta1,3Galbeta-cholestanols exerted a strong inhibiting activity against cell proliferation of esophageal cancer cells, but cholestanol itself did not show such an activity against the same cancer cells at all. In addition to their predominant role as an antiproliferation agent, evidence based on the molecular analyses suggested that sugar-cholestanols played a regulatory role in multiple signal transduction pathways inducing apoptosis through both the death signal-extrinsic and the mitochondria-intrinsic pathways. Sugar-cholestanols seemed to be more susceptible to esophageal cancer cells than to non-cancerous esophageal cells at the very early event of their exposure and, further, to suppress specifically the expression of vascular endothelial growth factor. Taken together, these novel functions of sugar-cholestanols indicate that they could have promising therapeutic potential against human esophageal cancer. more...

We report on the photophysical properties of 1,4-bis(2,2-diphenylethenyl)benzene (PEB) in a solution and a solid state. A poor blue photoluminescence efficiency of PEB in a solution dramatically increases in the deposited film. We explain such properties in terms of molecular dynamics and degrees of intramolecular freedom in various molecular environments. PEB as an electron-transport and emitting layer in organic light-emitting diodes (OLEDs) shows bright blue-green electroluminescence (EL) with the peak wavelength at λmax ~ 495 nm. The maximum external EL quantum efficiency of ηEL = 2.5 % and maximum luminance of 41600 cd/m2 in the optimized device were obtained, indicating that PEB possesses superior electron-transport ability. more...

Solid-state self-quenching processes of highly efficient Ir(III) phosphorescent emitters are investigated by the measurement of thin film photoluminescence quantum efficiency and transient lifetime as a function of doping concentration in a host matrix. The radiative decay rate constant is found to be independent from the average distance between dopant molecules (R), and the concentration-quenching rate constant is shown to be dependent on R(-6). The quenching dependence on R strongly suggests that luminescent concentration quenching in a phosphorescent Ir(III) complex:host film is controlled by dipole-dipole deactivating interactions as described by the Forster energy transfer model. more...

We succeeded in observing electroluminescence (EL) of 2,4-bis(4-(2′-thiophene-yl)phenyl)thio-phene (TPTPT) as an active layer in an organic field-effect transistor (OFET). In particular, an OFET with a short channel of dSD=0.8μm demonstrated higher EL efficiency than one with a much longer channel (dSD=9.8μm). We observed a maximum EL quantum efficiency (ηmax) of 6.4×10−3% in the short-channel-length device at an applied source-drain voltage of Vd=−100V and a gate voltage of Vg=−40V. From the OFET characteristics, although the TPTPT layer demonstrated typical p-type operation, the occurrence of EL clearly indicated simultaneous hole and electron injection from the source and drain electronics, respectively, under high Vd and Vg. more...

We succeeded in observing bright electroluminescence (EL) from 1wt%-rubrene doped tetraphenylpyrene (TPPy) as an active layer in a lateral organic light-emitting diode structure that allowed field-effect transistor operation. This device configuration provides an organic light-emitting diode structure where the anode (source) and cathode (drain) electrodes are laterally arranged, providing us a chance to control the EL intensity by changing the gate bias. We demonstrated that TPPy provides compatible transistor and EL characteristics. Further, not only rubrene doping into the TPPy host but also adjusting the source-drain channel length significantly improved the EL characteristics. We observed a maximum EL quantum efficiency (ηext) of ∼0.5% with a Cr∕Au source (S)-drain (D) electrode and a slightly higher ηext of ∼0.8% with S-D electrodes of MgAu∕Au, Al∕Au, Cr∕YAu∕Au, and MgAl∕Au multilayers, aiming for simultaneous hole and electron injection. more...