Co-reporter:Shinichi Kuno, Hiroshi Akeno, Hiroyuki Ohtani and Hideya Yuasa
Physical Chemistry Chemical Physics 2015 vol. 17(Issue 24) pp:15989-15995
Publication Date(Web):13 May 2015
DOI:10.1039/C5CP01203A
The afterglow of phosphorescent compounds can be distinguished from background fluorescence and scattered light by a time-resolved observation, which is a beneficial property for bioimaging. Phosphorescence emission accompanies spin-forbidden transitions from an excited singlet state through an excited triplet state to a ground singlet state. Since these intersystem crossings are facilitated usually by the heavy-atom effect, metal-free organic solids are seldom phosphorescent, although these solids have recently been refurbished as low-cost, eco-friendly phosphorescent materials. Here, we show that crystalline isophthalic acid exhibits room-temperature phosphorescence with an afterglow that lasts several seconds through a nuclear spin magnetism-assisted spin exchange of a radical ion pair. The obvious afterglow that facilitates a time-resolved detection and the unusual phosphorescence mechanism that enables emission intensification by nuclear spin managements are promising for exploiting the phosphorescence materials in novel applications such as bioimaging.
Co-reporter:Junji Takeuchi; Akihiro Ohkubo ; Hideya Yuasa
Chemistry – An Asian Journal 2015 Volume 10( Issue 3) pp:586-594
Publication Date(Web):
DOI:10.1002/asia.201403271
Abstract
For the development of a liposome that takes in and out a drug in response to stimuli, 2,4-diaminoxylose (Xyl), which allows stimuli-responsive conformational switches between 4C1 and 1C4, was incorporated into a lipid structure: Xyl derivatives with C8 and C16 methylene chains at the 1,3-positions (C8Xyl and C16Xyl) were synthesized. 1H NMR spectroscopy indicates that the addition of Zn2+ and then H+ induces conformational switches from the chair (4C1) to the reverse chair (1C4) and 1C4-to-4C1, respectively, at Xyl; this leads to transformation of the lipids between linear and bent structures. Osmotic pressure and electron microscopy studies demonstrate that C8Xyl in water forms spherical solid aggregates (C8Xyl−Zn), which are converted into liposomes (C8Xyl+Zn) upon the addition of Zn2+, and C16Xyl forms liposomes regardless of the presence of Zn2+. The aggregates of C8Xyl±Zn incorporated a fluorophore and only C8Xyl+Zn released the content upon the addition of HCl. This study shows that Xyl could be a stimuli-responsive component of a liposome.
Co-reporter:Junji Takeuchi; Akihiro Ohkubo ; Hideya Yuasa
Chemistry – An Asian Journal 2015 Volume 10( Issue 3) pp:
Publication Date(Web):
DOI:10.1002/asia.201590005
Co-reporter:Yu Liu, Takuya Kobayashi, Masayuki Iizuka, Tatsumi Tanaka, Izumi Sotokawa, Atsushi Shimoyama, Yasutoshi Murayama, Eigo Otsuji, Shun-ichiro Ogura, Hideya Yuasa
Bioorganic & Medicinal Chemistry 2013 Volume 21(Issue 11) pp:2832-2842
Publication Date(Web):1 June 2013
DOI:10.1016/j.bmc.2013.04.008
To create a novel high-throughput lectin assay (HTPLA) method based on the emission of a luminophore by highly penetrable near-infrared excitation, sugar-attached upconversion lanthanide nanoparticles (LNPs) were synthesized as a tool to highlight the aggregates caused by the sugar-mediated specific bridging between LNP and lectin. The emissions from a mannose-coated LNP in the aggregates with a mannose-binding lectin were much stronger than those from the non-aggregated samples, being sensitive enough for HTPLA. A galactose-coated LNP was also applicable to a macrophage aggregation assay for the sugar specificity of its surface lectin.The sugar-attached lanthanide nanoparticles are a novel tool for high throughput lectin assay, permitting rapid and facile detection of the sugar specific binding of lectins on the cell surface by near infrared excited emissions from the aggregations derived from the sugar–lectin bindings.
Co-reporter:Li-Ying Yang, Yuki Kawada, Lina Bai, Daijiro Kubota and Hideya Yuasa
Organic & Biomolecular Chemistry 2011 vol. 9(Issue 19) pp:6579-6586
Publication Date(Web):08 Jul 2011
DOI:10.1039/C1OB05775H
The synthesis of bioactive oligosaccharides is too tedious to scale up for commercialization. However, structurally simplified glycomimetics are commercializable, if they can be synthesized much more easily than the oligosaccharides while having a comparable bioactivity. In this study, we propose a 2-oxabutane (OB) structure as an imitation of the internal monosaccharide units in oligosaccharides. Two trimannoside and three pentamannoside OB-glycomimics were synthesized in remarkably short steps. Among them, Manα1-OB-2Man 10, a trimannoside mimic, showed eight-fold affinity toward concanavalin A (ConA) relative to methyl mannoside in latex agglutination lectin assay and equilibrium dialysis assay (EDA), while the other mimics showed three- to four-fold affinities. EDA indicated that the bindings between each mimic molecule and a ConA subsite were all in one-to-one stoichiometry and thus these mimics were monovalent ligands, excluding multivalence effect for the high affinities. The strong affinity of 10 could be explained by the occupation of two mannose binding sites of a ConA subsite by its two mannose units. Mimic 10 proved to be even a better ligand for ConA than the natural disaccharide Manα1,2Man, while been much more easy to synthesize, thereby illustrating the potential of the approach here presented.
Co-reporter:Li-Ying Yang, Tsuyoshi Haraguchi, Tomoka Inazawa, Susumu Kajiwara, Hideya Yuasa
Carbohydrate Research 2010 Volume 345(Issue 15) pp:2124-2132
Publication Date(Web):13 October 2010
DOI:10.1016/j.carres.2010.07.027
The synthesis of small glycoclusters with high affinity toward lectins is one of the important subjects in glycotechnology. Although cyclic α-(1→6)-d-octaglucoside (CI8) is an attractive scaffold on which to put glycosyl pendants, the compound has only secondary hydroxyl groups, which are relatively unreactive for substitution reactions. The oxidation of the vicinal diols of CI8 and reductive amination of the resultant dialdehydes with 2-aminoethyl mannoside gave mannose-CI8 conjugates with a variety of average mannose incorporation numbers (2–7). The average numbers were deduced from MALDI-TOF mass and 1H NMR spectroscopy. The binding ability of mannose-CI8 conjugates to concanavalin A increased with the increasing numbers of average mannose incorporation, reaching a plateau at tetravalence, as estimated from a latex bead-based agglutination lectin assay. Toxicity tests demonstrated the biocompatibility of mannose-CI8 conjugates.
Co-reporter:Nobuyuki Mitsuhashi
European Journal of Organic Chemistry 2009 Volume 2009( Issue 10) pp:1598-1605
Publication Date(Web):
DOI:10.1002/ejoc.200801285
Abstract
Conjugates of 2,4-diamino sugars and uridine have been synthesized as galactosyltransferase inhibitors. The relationship between inhibitory activity and the chelation abilility of the hinge-like diamino sugar towards a metal ion was studied by NMR spectroscopy. One of the conjugates exhibited a moderate inhibition that ranks between those of UDP and UMP probably through the chelation of the hinge-like diamino sugar to MnII. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Co-reporter:Hideya Yuasa, Naohiko Fujii and Shun Yamazaki
Organic & Biomolecular Chemistry 2007 vol. 5(Issue 18) pp:2920-2924
Publication Date(Web):02 Aug 2007
DOI:10.1039/B709115J
A hinge sugar, a 2,4-diamino-2,4-dideoxy-β-D-xylopyranoside derivative, turns its four equatorial substituents into axial orientations through a 4C1-to-1C4 ring flip in response to chelation to a metal ion. This hinge-like motion enables two components attached at the 1- and 3-positions to switch between far and near states. In this study, we examined the effect of N-alkylation on the bendability of the hinge molecule and synthesized a 2,4-dipyrenylmethyl derivative as a proton-selective sensor. 1H NMR studies showed that N-alkylations of the hinge sugar facilitated 1C4 formation in the presence of an acid, probably because the increased basicity of the amino group promoted the intramolecular hydrogen bond between the 2- and 4-amino substituents, whereas chelation to a metal ion was hampered by the increased bulkiness. In accordance with the above results, N,N′-dipyrenylmethyl hinge sugar 3 emitted excimer fluorescence (445 nm) owing to the pyrene stacking as a result of the 1C4 formation at lower concentrations of trifuluoroacetic acid (TFA), while no significant changes in fluorescence spectra were observed when metal ions were added. Increase of the monomer fluorescence (375 nm) at higher TFA concentrations was also observed. These observations indicate that 3 could be used as a proton-selective sensor that covers a wide range of proton concentrations through monitoring of the two fluorescence maxima.
Co-reporter:Hideya Yuasa, Masatoshi Nakatani and Hironobu Hashimoto
Organic & Biomolecular Chemistry 2006 vol. 4(Issue 19) pp:3694-3702
Publication Date(Web):30 Aug 2006
DOI:10.1039/B609115F
Methyl 3-O-p-methoxybenzyl-β-D-xylopyranoside (2) was exploited as a novel hinge-type tether for the [2 + 2] cycloaddition of cinnamate. The major ring conformation occupied by the 2,4-dicinnamate derivative of 2 was 4C1, which extends two cinnamates along a diequatorial orientation. However, 3-O-deprotected dicinnamate 5, when in a non-polar solvent, favours the 1C4 conformation, which assists the approach of two cinnamates with the 1,3-diaxial scaffold. Photoirradiation of compound 5 at 313 nm in CHCl3 afforded the intramolecular cycloaddition of cinnamates to give methyl β-, δ-, and ξ-truxinates in a 86 : 8 : 6 ratio after transesterification with methanol. The regio- and stereoselectivities are comparable to those reported by others for tethered cinnamates. The per-deuterated dicinnamate derivative of 5 facilitated the conformation analyses of the pyranoside rings by 1H NMR, indicating that all the products of photoirradiation had 1C4-fixed pyranosides. Excellent β-selectivity was achieved when m-bromocinnamate was subjected to hinge-tethered [2 + 2] cycloaddition.
Co-reporter:Hideya Yuasa ;Takuhiro Izumi;Nobuyuki Mitsuhashi;Yasuhiro Kajihara ;Hironobu Hashimoto
Chemistry - A European Journal 2005 Volume 11(Issue 22) pp:
Publication Date(Web):11 AUG 2005
DOI:10.1002/chem.200500096
Hinged di- and trisaccharides incorporating 2,4-diamino-β-D-xylopyranoside as a hinge unit (Hin) were synthesized. Bridging of the diamino group of Hin by carbonylation or chelation to a metal ion results in a conformational change from 4C1 to 1C4, which in turn causes a bending of the oligosaccharides. In this study, the bending abilities of the hinged oligosaccharides were compared, in terms of the reactivities toward carbonylation and chelation. Di- or trisaccharides containing a 6-O-glycosylated mannopyranoside or galactopyranoside at their reducing ends had bending abilities similar to that of the Hin monosaccharide, probably because there were neither attractive nor repulsive interactions between the reducing and nonreducing ends. However, when Hin was attached at O2 of methyl mannopyranoside (ManαMe), the bending ability was dependent on the nonreducing sugar and the reaction conditions. Typically, a disaccharide—Hinβ(1,2)ManαMe—was difficult to bend under all the tested reaction conditions, and the bent population in the presence of ZnII was only 4 %. On the other hand, a trisaccharide—Manα(1,3)Hinβ(1,2)ManαMe—was bent immediately after the addition of ZnII or HgII, and the bent population reached 75 %, much larger than those of all the other hinged trisaccharides ever tested (<40 %). This excellent bending ability suggests an attractive interaction between the reducing and nonreducing ends. The extended conformation was recovered by the addition of triethylenetetramine, a metal ion chelator. Reversible, quick, and efficient bending of the hinged trisaccharide was thus achieved.
Co-reporter:Takuhiro Izumi, Hironobu Hashimoto and Hideya Yuasa
Chemical Communications 2004 (Issue 1) pp:94-95
Publication Date(Web):20 Nov 2003
DOI:10.1039/B311811H
The bent conformation of a trisaccharide containing 2,4-diaminoxylopyranoside, in which both end sugars are presented in 1,3-diaxial orientation, is fixed by chelation of the diamino groups to Pt(II) and unfixed by a ligand exchange reaction with NaCN or thiourea giving its extended conformation.
Co-reporter:Hideya Yuasa, Naofusa Miyagawa, Masatoshi Nakatani, Masayuki Izumi and Hironobu Hashimoto
Organic & Biomolecular Chemistry 2004 vol. 2(Issue 24) pp:3548-3556
Publication Date(Web):18 Nov 2004
DOI:10.1039/B411344F
Carbohydrates are among the potential materials for molecular devices, since they are abundant natural resources. However, their rigidity has restricted their use for movable devices. Hinge sugars, 2,4-diamino-2,4-dideoxy-xylopyranosides, shed light on the use of carbohydrates as movable components, as demonstrated by the motion by which all four equatorial substituents can change to an axial orientation in synchronization with a chelation-driven 4C1–1C4 ring flip. In this study, we synthesized a tong-like metal ion sensor, 1,3-di-O-pyrenylmethylated hinge sugar (1), and its model compound, methyl 2,4-di-O-pyrenecarbonyl-xylopyranoside (2), to extend the abilities of hinge sugars as molecular components. From observations of the solvent-dependent conformational and fluorescent behavior of 2, we found that the pyrene stacking assists the 1C4 formation of xylopyranoside by 1.7 kcal mol−1. We also found that compound 1 produced excimer fluorescence by chelation to Pt2+, Zn2+, Cd2+, Mg2+ or Mn2+, and unexpectedly by addition of acids. 1H NMR measurements ascribed this behavior to the 4C1–1C4 ring flip of hinge sugar in response to chelation or protonation at N2, and revealed rapid and perfect 1C4 formation in the case of Zn2+. These findings will extend the scope of hinge sugars as movable components.
Co-reporter:Takashi Kanamori, Takashi Sawamura, Tatsumi Tanaka, Izumi Sotokawa, Ryota Mori, Kotaro Inada, Akihiro Ohkubo, Shun-Ichiro Ogura, Yasutoshi Murayama, Eigo Otsuji, Hideya Yuasa
Bioorganic & Medicinal Chemistry (15 January 2017) Volume 25(Issue 2) pp:
Publication Date(Web):15 January 2017
DOI:10.1016/j.bmc.2016.11.050
Lanthanide nanoparticles (LNPs) conjugated with monosaccharides were synthesized as a photon energy-upconverting nanodevice with affinity to cancer cells. The conjugates were designed to selectively damage the cancer cells containing protoporphyrin IX, a photosensitizer endogenously synthesized from priorly administrated 5-aminolevlunic acid (ALA), by a highly tissue-penetrative near-infrared (NIR) irradiation. First of all, the affinities of monosaccharides toward cells (HeLa, RAW264.7, and MKN45) were assessed by a novel cell aggregation assay with trivalent monosaccharide-citric acid conjugates. As a result, HeLa exhibited high affinity for glucose, while RAW264.7 for glucose, galactose, mannose, and fucose. A similar cell-monosaccharide affinity was microscopically observed when the cells were mixed with monosaccharide-LNP conjugates and rinsed, in which the high affinity LNP probes luminesced on the cells. The high affinity monosaccharide-LNPs showed greater photodamaging effects than the unmodified LNP toward the corresponding cells, when the cells were pretreated with ALA and irradiated by NIR. This study demonstrates that carbohydrates can be used as selective ligands for cancer cells in a photodynamic therapy with LNP.
Co-reporter:Shinichi Kuno, Hiroshi Akeno, Hiroyuki Ohtani and Hideya Yuasa
Physical Chemistry Chemical Physics 2015 - vol. 17(Issue 24) pp:NaN15995-15995
Publication Date(Web):2015/05/13
DOI:10.1039/C5CP01203A
The afterglow of phosphorescent compounds can be distinguished from background fluorescence and scattered light by a time-resolved observation, which is a beneficial property for bioimaging. Phosphorescence emission accompanies spin-forbidden transitions from an excited singlet state through an excited triplet state to a ground singlet state. Since these intersystem crossings are facilitated usually by the heavy-atom effect, metal-free organic solids are seldom phosphorescent, although these solids have recently been refurbished as low-cost, eco-friendly phosphorescent materials. Here, we show that crystalline isophthalic acid exhibits room-temperature phosphorescence with an afterglow that lasts several seconds through a nuclear spin magnetism-assisted spin exchange of a radical ion pair. The obvious afterglow that facilitates a time-resolved detection and the unusual phosphorescence mechanism that enables emission intensification by nuclear spin managements are promising for exploiting the phosphorescence materials in novel applications such as bioimaging.
Co-reporter:Li-Ying Yang, Yuki Kawada, Lina Bai, Daijiro Kubota and Hideya Yuasa
Organic & Biomolecular Chemistry 2011 - vol. 9(Issue 19) pp:NaN6586-6586
Publication Date(Web):2011/07/08
DOI:10.1039/C1OB05775H
The synthesis of bioactive oligosaccharides is too tedious to scale up for commercialization. However, structurally simplified glycomimetics are commercializable, if they can be synthesized much more easily than the oligosaccharides while having a comparable bioactivity. In this study, we propose a 2-oxabutane (OB) structure as an imitation of the internal monosaccharide units in oligosaccharides. Two trimannoside and three pentamannoside OB-glycomimics were synthesized in remarkably short steps. Among them, Manα1-OB-2Man 10, a trimannoside mimic, showed eight-fold affinity toward concanavalin A (ConA) relative to methyl mannoside in latex agglutination lectin assay and equilibrium dialysis assay (EDA), while the other mimics showed three- to four-fold affinities. EDA indicated that the bindings between each mimic molecule and a ConA subsite were all in one-to-one stoichiometry and thus these mimics were monovalent ligands, excluding multivalence effect for the high affinities. The strong affinity of 10 could be explained by the occupation of two mannose binding sites of a ConA subsite by its two mannose units. Mimic 10 proved to be even a better ligand for ConA than the natural disaccharide Manα1,2Man, while been much more easy to synthesize, thereby illustrating the potential of the approach here presented.
Co-reporter:Hideya Yuasa, Naohiko Fujii and Shun Yamazaki
Organic & Biomolecular Chemistry 2007 - vol. 5(Issue 18) pp:NaN2924-2924
Publication Date(Web):2007/08/02
DOI:10.1039/B709115J
A hinge sugar, a 2,4-diamino-2,4-dideoxy-β-D-xylopyranoside derivative, turns its four equatorial substituents into axial orientations through a 4C1-to-1C4 ring flip in response to chelation to a metal ion. This hinge-like motion enables two components attached at the 1- and 3-positions to switch between far and near states. In this study, we examined the effect of N-alkylation on the bendability of the hinge molecule and synthesized a 2,4-dipyrenylmethyl derivative as a proton-selective sensor. 1H NMR studies showed that N-alkylations of the hinge sugar facilitated 1C4 formation in the presence of an acid, probably because the increased basicity of the amino group promoted the intramolecular hydrogen bond between the 2- and 4-amino substituents, whereas chelation to a metal ion was hampered by the increased bulkiness. In accordance with the above results, N,N′-dipyrenylmethyl hinge sugar 3 emitted excimer fluorescence (445 nm) owing to the pyrene stacking as a result of the 1C4 formation at lower concentrations of trifuluoroacetic acid (TFA), while no significant changes in fluorescence spectra were observed when metal ions were added. Increase of the monomer fluorescence (375 nm) at higher TFA concentrations was also observed. These observations indicate that 3 could be used as a proton-selective sensor that covers a wide range of proton concentrations through monitoring of the two fluorescence maxima.
![1-[5-O-[BIS(4-METHOXYPHENYL)BENZYL]-3-O-[[BIS(1-METHYLETHYL)AMINO](2-CYANOETHOXY)PHOSPHINO]-2-DEOXY-D-ERYTHRO-PENTOFURANOSYL]-5-METHYL-4-(1H-1,2,4-TRIAZOL-1-YL)-2(1H)-PYRIMIDINONE](http://img.cochemist.com/ccimg/101800/101712-10-1.png)
![1-[5-O-[BIS(4-METHOXYPHENYL)BENZYL]-3-O-[[BIS(1-METHYLETHYL)AMINO](2-CYANOETHOXY)PHOSPHINO]-2-DEOXY-D-ERYTHRO-PENTOFURANOSYL]-5-METHYL-4-(1H-1,2,4-TRIAZOL-1-YL)-2(1H)-PYRIMIDINONE](http://img.cochemist.com/ccimg/101800/101712-10-1_b.png)
