Seiichi Uchiyama

The University of Tokyo, Edo, Tōkyō, Japan

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Publications (52)266.09 Total impact

  • Kyoko Kawamoto, Seiichi Uchiyama
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    ABSTRACT: The synthesis and properties of new fluorogenic benzothiadiazole and benzoselanadiazole reagents (II) are described.
    ChemInform 04/2013; 44(14).
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    ABSTRACT: Chemical mitochondrial uncouplers are lipophilic weak acids that increase proton transport into the mitochondrial matrix via a pathway independent of ATP synthase, thereby uncoupling nutrient oxidation from ATP production. These molecules enable determination of maximal cellular respiration and have antioxidant effects that protect from ischemia-reperfusion injury. However, the most widely used proton transporter uncouplers have off-target activity that leads to a range of undesired effects including plasma membrane depolarization, mitochondrial inhibition, and cytotoxicity. To identify new mitochondrial uncouplers that lack off-target activity at the plasma membrane, we screened a small molecule chemical library. Herein we report the identification and validation of a novel mitochondrial protonophore uncoupler (2-fluorophenyl){6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4–e]pyrazin-5-yl)}amine, named BAM15, that does not depolarize the plasma membrane and protects mice from acute renal ischemic-reperfusion injury. Thus, BAM15 represents a reliable new tool for the analysis of cellular bioenergetic function that has therapeutic potential by altering mitochondrial function in vivo.
    Molecular Metabolism. 01/2013;
  • Biophysical Journal 01/2013; 104(2):201-. · 3.83 Impact Factor
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    ABSTRACT: An environment-sensitive fluorophore can change its maximum emission wavelength (λ(em)), fluorescence quantum yield (Φ(f)), and fluorescence lifetime in response to the surrounding environment. We have developed two new intramolecular charge-transfer-type environment-sensitive fluorophores, DBThD-IA and DBSeD-IA, in which the oxygen atom of a well-established 2,1,3-benzoxadiazole environment-sensitive fluorophore, DBD-IA, has been replaced by a sulfur and selenium atom, respectively. DBThD-IA is highly fluorescent in n-hexane (Φ(f) =0.81, λ(em) =537 nm) with excitation at 449 nm, but is almost nonfluorescent in water (Φ(f) =0.037, λ(em) =616 nm), similarly to DBD-IA (Φ(f) =0.91, λ(em) =520 nm in n-hexane; Φ(f) =0.027, λ(em) =616 nm in water). A similar variation in fluorescence properties was also observed for DBSeD-IA (Φ(f) =0.24, λ(em) =591 nm in n-hexane; Φ(f) =0.0046, λ(em) =672 nm in water). An intensive study of the solvent effects on the fluorescence properties of these fluorophores revealed that both the polarity of the environment and hydrogen bonding with solvent molecules accelerate the nonradiative relaxation of the excited fluorophores. Time-resolved optoacoustic and phosphorescence measurements clarified that both intersystem crossing and internal conversion are involved in the nonradiative relaxation processes of DBThD-IA and DBSeD-IA. In addition, DBThD-IA exhibits a 10-fold higher photostability in aqueous solution than the original fluorophore DBD-IA, which allowed us to create a new robust molecular nanogel thermometer for intracellular thermometry.
    Chemistry - A European Journal 07/2012; 18(31):9552-63. · 5.93 Impact Factor
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    ABSTRACT: A coumarin analogue, 8-methoxy-4-methyl-2H-benzo[g]chromen-2-one (MMBC), is almost non-fluorescent in non-polar media, whereas it exhibits dramatically enhanced fluorescence in polar protic solvents. This study investigates the mechanistic features of the significant solvent effects on the fluorescence properties of MMBC and a related compound, 4-methyl-2H-benzo[g]chromen-2-one (MBC), by time-resolved fluorescence and photoacoustic measurements and by theoretical calculations. Time-resolved photoacoustic measurements reveal that the extremely fast non-radiative processes of MBC and MMBC in non-polar solvents can be attributed predominantly to internal conversion. The internal conversion rates of MBC and MMBC are remarkably reduced in a rigid matrix of 3-methylpentane at 77 K, suggesting that internal conversion is a thermally activated process. The photophysical properties of MBC and MMBC examined in selected solvents with different polarities and hydrogen-bond donating abilities show that the internal conversion rate is greatly reduced by hydrogen-bonding interactions with protic solvents. Furthermore, remarkable fluorescence enhancement is observed by adding a small amount of trifluoroethanol to n-hexane solutions of MBC and MMBC, indicating that internal conversion is suppressed by formation of hydrogen-bonded complexes with protic solvents. In light of theoretical considerations based on time-dependent density functional theory (TD-DFT) and INDO/S-CI calculations, the occurrence of fast internal conversion in MBC and MMBC can be explained in terms of the proximity effect, i.e., pseudo Jahn-Teller coupling between energetically close S(1) and S(2) states.
    Photochemical and Photobiological Sciences 06/2012; 11(8):1368-76. · 2.92 Impact Factor
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    ABSTRACT: Cellular functions are fundamentally regulated by intracellular temperature, which influences biochemical reactions inside a cell. Despite the important contributions to biological and medical applications that it would offer, intracellular temperature mapping has not been achieved. Here we demonstrate the first intracellular temperature mapping based on a fluorescent polymeric thermometer and fluorescence lifetime imaging microscopy. The spatial and temperature resolutions of our thermometry were at the diffraction limited level (200 nm) and 0.18-0.58 °C. The intracellular temperature distribution we observed indicated that the nucleus and centrosome of a COS7 cell, both showed a significantly higher temperature than the cytoplasm and that the temperature gap between the nucleus and the cytoplasm differed depending on the cell cycle. The heat production from mitochondria was also observed as a proximal local temperature increase. These results showed that our new intracellular thermometry could determine an intrinsic relationship between the temperature and organelle function.
    Nature Communications 02/2012; 3:705. · 10.74 Impact Factor
  • Biophysical Journal 01/2012; 102(3):198-. · 3.83 Impact Factor
  • A Prasanna de Silva, Seiichi Uchiyama
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    ABSTRACT: The competition between Photoinduced electron transfer (PET) and other de-excitation pathways such as fluorescence and phosphorescence can be controlled within designed molecular structures. Depending on the particular design, the resulting optical output is thus a function of various inputs such as ion concentration and excitation light dose. Once digitized into binary code, these input-output patterns can be interpreted according to Boolean logic. The single-input logic types of YES and NOT cover simple sensors and the double- (or higher-) input logic types represent other gates such as AND and OR. The logic-based arithmetic processors such as half-adders and half-subtractors are also featured. Naturally, a principal application of the more complex gates is in multi-sensing contexts.
    Topics in current chemistry 01/2011; 300:1-28. · 4.61 Impact Factor
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    ABSTRACT: The use of a water-soluble, thermo-responsive polymer as a highly sensitive fluorescence-lifetime probe of microfluidic temperature is demonstrated. The fluorescence lifetime of poly(N-isopropylacrylamide) labelled with a benzofurazan fluorophore is shown to have a steep dependence on temperature around the polymer phase transition and the photophysical origin of this response is established. The use of this unusual fluorescent probe in conjunction with fluorescence lifetime imaging microscopy (FLIM) enables the spatial variation of temperature in a microfluidic device to be mapped, on the micron scale, with a resolution of less than 0.1 degrees C. This represents an increase in temperature resolution of an order of magnitude over that achieved previously by FLIM of temperature-sensitive dyes.
    Lab on a Chip 05/2010; 10(10):1267-73. · 5.75 Impact Factor
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    ABSTRACT: A novel fluorimetric method for determining radicals using the natural phenol sesamol as a fluorogenic reagent is reported. In this assay, sesamol was reacted with aqueous radicals to yield one isomer of a sesamol dimer exclusively. The dimer emitted purple fluorescence near 400 nm around neutral pH, where it assumed the monoanionic form. This method was applied to the straightforward detection of radical nitric oxide (NO). The ready availability of sesamol should enable rapid implementation of applications utilizing this new assay, particularly in high-throughput analysis or screening.
    Analytical Chemistry 02/2010; 82(4):1213-20. · 5.83 Impact Factor
  • Seiichi Uchiyama, Yumi Makino
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    ABSTRACT: We designed polymeric sensors that created a digital-type fluorescence response to pH variation in an aqueous solution.
    Chemical Communications 06/2009; · 6.72 Impact Factor
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    ABSTRACT: The first methodology to measure intracellular temperature is described. A highly hydrophilic fluorescent nanogel thermometer developed for this purpose stays in the cytoplasm and emits stronger fluorescence at a higher temperature. Thus, intracellular temperature variations associated with biological processes can be monitored by this novel thermometer with a temperature resolution of better than 0.5 degrees C.
    Journal of the American Chemical Society 03/2009; 131(8):2766-7. · 11.44 Impact Factor
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    ABSTRACT: Fluorescent molecular thermometers showing temperature-dependent fluorescence lifetimes enable thermal mapping of small spaces such as a microchannel and a living cell. We report the temperature-dependent fluorescence lifetimes of poly(NIPAM-co-DBD-AA), which is a random copolymer of N-isopropylacrylamide (NIPAM) and an environment-sensitive fluorescent monomer (DBD-AA) containing a 4-sulfamoyl-7-aminobenzofurazan structure. The average fluorescence lifetime of poly(NIPAM-co-DBD-AA) in aqueous solution increased from 4.22 to 14.1 ns with increasing temperature from 30 to 35 degrees C. This drastic change in fluorescence lifetime (27% increase per 1 degrees C) is the sharpest ever reported. Concentration independency, one of the advantages of fluorescence lifetime measurements, was seen in average fluorescence lifetime (13.7 +/- 0.18 ns) of poly(NIPAM-co-DBD-AA) at 33 degrees C over a wide concentration range (0.005-1 w/v%). With increasing temperature, polyNIPAM units in poly(NIPAM-co-DBD-AA) change their structure from an extended form to a globular form, providing apolar and aprotic environments to the fluorescent DBD-AA units. Consequently, the environment-sensitive DBD-AA units translate the local environmental changes into the extension of the fluorescence lifetime. This role of the DBD-AA units was revealed by a study of solvent effects on fluorescence lifetime of a model environment-sensitive fluorophore.
    The Journal of Physical Chemistry B 04/2008; 112(10):2829-36. · 3.38 Impact Factor
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    Seiichi Uchiyama, Kaoru Iwai, A Prasanna de Silva
    Angewandte Chemie International Edition 02/2008; 47(25):4667-9. · 11.34 Impact Factor
  • Seiichi Uchiyama, Kaoru Iwai
    Angewandte Chemie. 01/2008; 120(25):4687-4687.
  • Seiichi Uchiyama, Kaoru Iwai
    Angewandte Chemie International Edition 01/2008; 47(25):4609-4609. · 11.34 Impact Factor
  • Maki Onoda, Seiichi Uchiyama, Tomohiko Ohwada
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    ABSTRACT: We have developed fluorogenic (fluorescent off-on) ion sensors of a new type, based on stimulus-responsive synthetic copolymers incorporating a polarity-sensitive fluorophore. Upon binding a target ion in aqueous solution, these macromolecular fluorogenic sensors change their three-dimensional structure from an open form to a globular form at functional temperatures, and this induces a change of microenvironmental polarity around the polarity-sensitive fluorophore. The fluorophore transforms this environmental polarity change into a fluorescence signal. Our polymeric sensors were prepared by random copolymerization of comonomers selected from four types of comonomers. First, the role of each type of comonomer in the polymeric sensors was examined through the development of a fluorogenic H+ sensor. Next, a fluorogenic K+ ion sensor was developed in order to demonstrate the generality of this “buildup” design concept. Finally, a fluorogenic SO42- sensor working in water was developed for the first time.
    Macromolecules 11/2007; 40(26). · 5.93 Impact Factor
  • Seiichi Uchiyama, Chie Gota
    Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme 11/2007; 52(13 Suppl):1608-12.
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    ABSTRACT: The ideas of supramolecular chemistry can be a useful way of advancing molecular logic and computation. Some of these cases occur at the molecular-scale while others require the intervention of bulk materials of various kinds. Even irreversible chemical reactions can provide food for thought. Logic operations from the simplest to small-scale integrated cases are now available, including those with arithmetic capability.
    Coordination Chemistry Reviews 07/2007; · 12.10 Impact Factor
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    A Prasanna de Silva, Seiichi Uchiyama
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    ABSTRACT: Molecular substrates can be viewed as computational devices that process physical or chemical 'inputs' to generate 'outputs' based on a set of logical operators. By recognizing this conceptual crossover between chemistry and computation, it can be argued that the success of life itself is founded on a much longer-term revolution in information handling when compared with the modern semiconductor computing industry. Many of the simpler logic operations can be identified within chemical reactions and phenomena, as well as being produced in specifically designed systems. Some degree of integration can also be arranged, leading, in some instances, to arithmetic processing. These molecular logic systems can also lend themselves to convenient reconfiguring. Their clearest application area is in the life sciences, where their small size is a distinct advantage over conventional semiconductor counterparts. Molecular logic designs aid chemical (especially intracellular) sensing, small object recognition and intelligent diagnostics.
    Nature Nanotechnology 07/2007; 2(7):399-410. · 31.17 Impact Factor

Publication Stats

1k Citations
266.09 Total Impact Points


  • 1998–2013
    • The University of Tokyo
      • • Department of Pharmaceutical Sciences
      • • Faculty and Graduate School of Pharmaceutical Sciences
      Edo, Tōkyō, Japan
  • 2005–2011
    • Queen's University Belfast
      • School of Chemistry and Chemical Engineering
      Belfast, NIR, United Kingdom
  • 2008
    • Queen's University
      Kingston, Ontario, Canada
  • 2003–2005
    • Nara Women's University
      • Department of Chemistry
      Nara, Nara, Japan