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Biomedical subjects

Kentaro Yamaguchi

Publications and source records attributed to Kentaro Yamaguchi.

At least 109 records · Page 6Linked to original sources
PubMed2002

Allosteric Binding of an Ag+ Ion to Cerium(IV) Bis-porphyrinates Enhances the Rotational Activity of Porphyrin Ligands.

A series of cerium(IV) bis-porphyrinate double-deckers [Ce(bbpp)(2)] (BBPP=5,15-bis(4-butoxyphenyl)porphyrin dianion), [Ce(tmpp)(2)] (TMPP=5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin dianion), [Ce(tfpp)(2)] (TFPP=5,10,15,20-tetrakis(4-fluorophenyl)porphyrin dianion), [Ce(tmcpp)(2)] (TMCPP=5,10,15,20-tetrakis(4-methoxycarbonylphenyl)porphyrin dianion), and [Ce(tmpp)(tmcpp)] was prepared. They bind three Ag(+) ions to their concave porphyrin pi subunits (pi-clefts) according to a positive homotropic allosteric mechanism with Hill coefficients (n(H)) of 1.7-2.7. The rotation rates of the porphyrin ligands in [Ce(bbpp)(2)] were evaluated to be 200 s(-1) at 20 degrees C (DeltaG$\rm{^{\ne }_{293}}$=14.1 kcal mol(-1)) and 220 s(-1) at -40 degrees C (DeltaG$\rm{^{\ne }_{233}}$=11.0 kcal mol(-1)) without and with Ag(+) ions, respectively. These results consistently support our unexpected finding that Ag(+) binding can accelerate rotation of the porphyrin ligand. On the basis of UV-visible, (1)H NMR, and resonance Raman spectral measurements, the rate enhancement of the rotational speed of the porphyrin ligands is attributed to conformational changes of the porphyrin in cerium(IV) bis-porphyrinate induced by binding of Ag(+) guest ions in the clefts. This novel concept of positive homotropic allosterism is applicable to the molecular design of various supramolecular and switch-functionalized systems.

Journal Article↗
PubMed2002

Allosteric binding of an Ag+ ion to cerium(IV) bis-porphyrinates enhances the rotational activity of porphyrin ligands.

A series of cerium(IV) bisporphyrinate double-deckers [Ce(bbpp)2] (BBPP = 5,15-bis(4-butoxyphenyl) porphyrin dianion), [Ce(tmpp)2] (TMPP = 5,10,15,20-tetrakis(4-methoxyphenyl)-porphyrin dianion), [Ce(tfpp)2] (TFPP = 5,10,15,20-tetrakis(4-fluorophenyl)porphyrin dianion), [Ce(tmcpp)2] (TMCPP = 5,10,15,20-tetrakis(4-methoxycarbonylphenyl)porphyrin dianion), and [Ce(tmpp)(tmcpp)] was prepared. They bind three Ag+ ions to their concave porphyrin pi subunits (pi-clefts) according to a positive homotropic allosteric mechanism with Hill coefficients (nH) of 1.7-2.7. The rotation rates of the porphyrin ligands in [Ce(bbpp)2] were evaluated to be 200 s-1 at 20 degrees C (delta G++293 = 14.1 kcal mol-1) and 220 s-1 at -40 degrees C (delta G++233 = 11.0 kcal mol-1) without and with Ag+ ions, respectively. These results consistently support our unexpected finding that Ag+ binding can accelerate rotation of the porphyrin ligand. On the basis of UV-visible, 1H NMR, and resonance Raman spectral measurements, the rate enhancement of the rotational speed of the porphyrin ligands is attributed to conformational changes of the porphyrin in cerium(IV) bis-porphyrinate induced by binding of Ag+ guest ions in the clefts. This novel concept of positive homotropic allosterism is applicable to the molecular design of various supramolecular and switch-functionalized systems.

Journal Article↗
PubMed2002

Synthesis and muscarinic M(2) subtype antagonistic activity of enantiomeric pairs of 3-demethylhimbacine (3-norhimbacine) and its C(4)-epimer.

In the course of our studies of the structure-activity relationships of himbacine 1, a potent antagonist of the M(2) subtype of muscarinic receptor, the four title compounds, 2, ent-2, 3, and ent-3, were synthesized with a highly stereoselective intermolecular Diels-Alder reaction of tetrahydroisobenzofuran 4 with achiral furan-2(5H)-one 5 as a key step, followed by simultaneous optical resolution and epimer separation of the racemic intermediates. Among these compounds, 3-demethylhimbacine (3-norhimbacine) 2, bearing an absolute configuration corresponding to that of 1, was found to show more potent muscarinic M(2) subtype receptor binding activity than natural 1.

Alkaloids↗
PubMed2002

A supramolecular oscillator composed of carbon nanocluster C(120) and a rhodium(III) porphyrin cyclic dimer.

A rhodium(III) porphyrin cyclic dimer (1) included carbon nanocluster C120 (2) to form a pi-electronic supramolecular complex (1 superset2), in which 2 oscillated back and forth within its cavity. Spectroscopic titration of 1 with 2 and line shape analysis on variable-temperature 1H NMR spectral profiles of 1 superset2 and reference inclusion complexes in toluene-d8, chlorobenzene-d5, and dichlorobenzene-d4 indicated that the association constant (Kassoc) of 1 superset2 and oscillation activity of included 2 are both larger as the affinity of the solvent toward fullerenes is smaller. The DeltaS values for the oscillation were all positive, indicating that the oscillation of 2 involves desolvation of a protruding C60 moiety of included 2 from the host cavity.

Journal Article↗
PubMed2002

Enhanced radical-scavenging activity of a planar catechin analogue.

A catechin analogue in which the geometry was constrained to be planar was synthesized. The planar catechin showed excellent radical-scavenging ability, comparable to that of quercetin, and efficient protection against DNA strand breakage induced by the Fenton reaction.

Antioxidants↗
PubMed2002

Guest-induced organization of an optimal receptor from a dynamic receptor library: spectroscopic screening.

Complexation of a cis-protected palladium ion and a family of exo-bidentate and -tridentate ligands results in the formation of an equilibrium mixture of numerous metal-linked receptors that are referred to as a dynamic receptor library. We found that a guest induced the selective formation of the optimal receptor of its own. Screening of the library by using difference NMR facilitates the search for new receptors because in difference NMR only receptors interacting with the guest can be observed. An unpredictable heterotopic receptor was discovered by this screening method. Interestingly, the new receptor thus found was assembled quantitatively only in the presence of its optimal guest.

Chemistry↗
PubMed2002

Designed self-assembly of molecular necklaces.

This paper reports an efficient strategy to synthesize molecular necklaces, in which a number of small rings are threaded onto a large ring, utilizing the principles of self-assembly and coordination chemistry. Our strategy involves (1) threading a molecular "bead" with a short "string" to make a pseudorotaxane and then (2) linking the pseudorotaxanes with a metal complex with two cis labile ligands acting as an "angle connector" to form a cyclic product (molecular necklace). A 4- or 3-pyridylmethyl group is attached to each end of 1,4-diaminobutane or 1,5-diaminopentane to produce the short "strings" (C4N4(2+), C4N3(2+), C5N4(2+), and C5N3(2+)), which then react with a cucurbituril (CB) "bead" to form stable pseudorotaxanes (PR44(2+), PR43(2+), PR54(2+), and PR53(2+), respectively). The reaction of the pseudorotaxanes with Pt(en)(NO(3))(2) (en = ethylenediamine) produces a molecular necklace [4]MN, in which three molecular "beads" are threaded on a triangular framework, and/or a molecular necklace [5]MN, in which four molecular "beads" are threaded on a square framework. Under refluxing conditions, the reaction with PR44(2+) or PR54(2+) yields exclusively [4]MN (MN44T or MN54T, respectively), whereas that with PR43(2+) or PR53(2+) produces exclusively [5]MN (MN43S or MN53S, respectively). The products have been characterized by various methods including X-ray crystallography. At lower temperatures, on the other hand, the reaction with PR44(2+) or PR54(2+) affords both [4]MN and [5]MN. The supermolecules reported here are the first series of molecular necklaces obtained as thermodynamic products. The overall structures of the molecular necklaces are strongly influenced by the structures of pseudorotaxane building blocks, which is discussed in detail on the basis of the X-ray crystal structures. The temperature dependence of the product distribution observed in this self-assembly process is also discussed.

Journal Article↗
PubMed2002

Design and synthesis of an enzyme-cleavable sensor molecule for phosphodiesterase activity based on fluorescence resonance energy transfer.

Ratiometric measurement is a technique that can provide precise data and even quantitative detection. To carry out ratiometric measurements, it is necessary that the sensor molecule exhibits a large shift in its emission or excitation spectrum after reaction with the target molecule. Fluorescence resonance energy transfer (FRET) is one mechanism used to obtain a large spectral shift. In this study, our aim was to develop a ratiometric fluorescent sensor molecule for phosphodiesterase activity based on FRET. We designed and synthesized CPF4 with a coumarin donor, a fluorescein acceptor, and two phenyl linkers having the phosphodiester moiety interposed between them. In the emission spectrum of CPF4 in aqueous buffer excited at 370 nm, the emission of the coumarin donor was strongly quenched and the emission of the fluorescein acceptor was observed. This emission spectrum demonstrates that energy transfer from the coumarin donor to the fluorescein acceptor proceeds efficiently. Addition of a phosphodiesterase to an aqueous solution of CPF4 resulted in an increase in the donor fluorescence and a decrease in the acceptor fluorescence. CPF4 exhibited a large shift in its emission spectrum after the hydrolysis of the phosphodiester group by the enzyme. This large shift of the emission spectrum indicates that ratiometric measurements can be made by using CPF4. The method described in this paper for designing enzyme-cleavable sensor molecules based on FRET should be readily applicable to other hydrolytic enzymes.

Biosensing Techniques↗
PubMed2002

Novel superstructure of nondiscoid mesogens: uneven-parallel association of half-disk molecules, 3,4,5-trialkoxybenzoic anhydrides, to a columnar structure and its one-directionally geared interdigitation.

Compact and simple nondiscoid mesogens, trialkoxybenzoic anhydrides 2-11 ((RO)(3)C(6)H(2)-CO-O-CO-C(6)H(2)(OR)(3), R = C(2)H(5), n-C(3)H(7), n-C(4)H(9), n-C(6)H(13), n-C(8)H(17), n-C(10)H(21), n-C(12)H(25), n-C(14)H(29), n-C(16)H(33), and (S)- and (R)-3,7-dimethyloctyl) were designed and synthesized, and their superstructures were investigated by polarized light microscopy, differential scanning calorimetry, calculation (MM2 and AM1), circular dichroism spectroscopy, and X-ray diffraction. As the result, in the cases of 5-9 and 11, the half-disk molecules in the liquid crystal phases were self-assembled by the dipole-dipole interaction between their carbonyl groups to a column in which the molecules were piled up in an alternately antiparallel manner, and the columns were interdigitated each other. The observed interdigitations were highly directional in the perpendicular direction to the column axis. In the case of compound 11 which has (S)- or (R)-3,7-dimethyloctyl groups, a helical organization of the molecules in the column was estimated from the peaks in the circular dichroism spectra. This is the first report of a one-directionally interdigitated columnar phase, and these compounds are the first liquid crystalline acid anhydrides. It was demonstrated that a -CO-O-CO- moiety is useful as a polar junction in liquid crystalline compounds.

Journal Article↗
PubMed2002

Cyclic dibenzoylhydrazines reproducing the conformation of ecdysone agonists, RH-5849.

We have investigated the biologically active conformation of the non-steroidal ecdysone agonist, 1-tert-butyl-1,2-dibenzoylhydrazine (RH-5849) by means of design, synthesis and conformational analysis of cyclic derivatives of RH-5849. Among the synthesized compounds, a 6-membered cyclic hydrazine bearing two benzoyl groups (5) exists in three conformational states in solution, and the major unsymmetrical conformer of 5 is similar to that of RH-5849 on the basis of 1H NMR and X-ray analyses. The 3,3-dimethyl derivative of 5 (10) exists as a single unsymmetrical conformer. Although there is conformational similarity of the cyclic derivatives with RH-5849, these compounds did not show any hormonal or insecticidal activity. The hydrogen bonding character of the amide N-H group of the dibenzoylhydrazine seems to play a critical role in the appearance of the biological activity.

Animals↗
PubMed2002

Design and synthesis of a novel magnetic resonance imaging contrast agent for selective sensing of zinc ion.

A series of new diethylenetriaminepentaacetic acid (DTPA)-bisamide chelators has been prepared and characterized for application as zinc sensors. We have designed and synthesized (GdL(a))(2-), which contains a DTPA-bisamide moiety. The R(1) relaxivity of (GdL(a))(2-) solution decreased monotonically on the addition of Zn(2+). Moreover, (GdL(a))(2-) showed high selectivity for Zn(2+) against Ca(2+) and Mg(2+). We also measured the UV-visible spectra and the coldspray ionization (CSI) MS spectra and concluded that the 1-to-1 Zn(2+) complex of (GdL(a))(2-) is stable at higher concentrations of Zn(2+). These complexes should provide the basis for creating a superior Zn(2+)-sensitive MRI contrast agent and are excellent candidates for incorporation into sensors designed for selective detection of Zn(2+) in biological applications.

Cations↗
PubMed2002

Crystal structure of the alcoholates and the ansolvate of PNU-97018, an angiotensin II receptor antagonist.

The title compound, PNU-97018 [systemic name: 2-butyl-3,6,7,8,9,11-hexahydro-6,9-dimethyl-3-([2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl)-6,9-ethano-4H-imidazo[4,5-d]-pyridazino[1,2-a]pyridazin-4-one] is a newly developed angiotensin II receptor antagonist. The compound and its methanolate and ethanolate were characterized by X-ray crystallography and thermal analysis. The methanolate and ethanolate crystals have an almost identical molecular conformation and crystal packing. In both alcoholates, each alcohol molecule is fixed to the compound with a molar ratio of 1 : 1 by a hydrogen bond between the hydroxyl group of the alcohol molecule and the tetrazole group of the compound. The hydroxyl group of each alcohol molecule further links with the imidazole ring of the neighboring compound by hydrogen bond to form a hydrogen-bond network in both alcoholates. A tunnel-like structure that includes alcohol molecules is formed in each alcoholate. The ansolvate crystal showed completely different thermal and X-ray crystallographic characteristics from the alcoholates, where the compound molecules were directly linked by hydrogen bonds between the tetrazole group of a molecule and the imidazole ring of the neighboring molecule. The position of the hydrogen atom in the tetrazole ring was different between the ansolvate and alcoholates. Unlike alcoholates, a layer structure stacked on the b-c plane was observed in the ansolvate crystal. It was concluded that the molecular conformation and the arrangement of the compound molecules were largely different between ansolvate and alcoholate crystals.

Alcohols↗