Biomedical subjects
Publications and source records attributed to Kentaro Yamaguchi.
A new alkaloid, lycoposerramine-B (1), containing an oxime function, was isolated from the club moss Lycopodium serratum Thunb. The structure of 1 was elucidated by spectroscopic analysis, including J-resolved HMBC spectroscopy, and confirmed by its synthesis from the known alkaloid, serratinine (3).
The syntheses of various types of hexakis(4-functionalized-phenyl)benzenes 1 and hexakis[4-(4'-functionalized-phenylethynyl)phenyl]benzenes 2 by the cobalt-catalyzed cyclotrimerization of diarylacetylenes and by the Sonogashira coupling reaction of 1e with arylacetylenes, respectively, are described. X-ray crystallographic analysis showed that host 1e or 2f forms a 2-D network by unique I...I or CH...O=C interactions, respectively.
Four new ent-halimane diterpenes (1-4) and one new guaiane sesquiterpene (5) were isolated from the CHCl(3) extract of the roots of Cladogynos orientalis, together with six known compounds. The structures of compounds 1-5 were established using spectroscopic methods, and the stereochemistry of chettaphanin I (6) was confirmed by X-ray crystallography.
The investigation of the host-guest complex formations between cyclophane (TGDMAP) (1) as a host and L-acidic amino acids such as L-glutamic acid (Glu) and L-aspartic acid (Asp) as guests was carried out using fast atom bombardment (FAB), electrospray ionization (ESI) and cold-spray ionization (CSI) mass spectrometry (MS). The stability constant (K(s)) values obtained by the three different MS methods almost agreed. However, the complex ion peaks of a novel cyclophane (CPCn) (2) with Glu and Asp were not observed in FAB-MS. Then, these host-guest complex formations by use of CSI-MS and ESI-MS was examined, as the results, these complex ion peaks were observed clearly and the measurement values by the two MS methods are mostly in agreement. It was concluded that ESI-MS and CSI-MS are available for the determination of K(s) value as well as FAB-MS.
An extensive analysis of hydrogen bonding of steroid compounds in diluted solution is preformed by pulsed field gradient (PFG) NMR and cold-spray ionization (CSI)-MS, in the solid state by X-ray crystallographic analysis. The formation of hydrogen bond interaction are quantified and discussed. Although X-ray analysis in the crystalline state and CSI-MS measurement in solution suggested that the observed diffusion coefficient D(obs) of the steroid compounds may vary in accordance with the number of hydrogen bonds, the actual observed D(obs) value determined from the diffusion studies diminished constantly without correlation on the decreasing numbers of hydrogen bonds. Comparison of two different calibration profiles of calculated molecular volume (V(cal)) vs. D(obs), which are obtained from compounds possessing no hydrogen bonding and the steroid compounds, formation of a chain structure (cluster) based on intermolecular hydrogen bonding of the steroid compounds is unambiguously confirmed.
The characterization of water molecules bound to ribonuclease T1 (RNase T1) was carried out using cold-spray ionization mass spectrometry (CSI-MS). CSI-MS is a variant of electrospray ionization mass spectrometry (ESI-MS) operating at low temperature, and is particularly suitable for investigating the weaker molecular associations, since the temperature at the spray interface is much lower than that in the conventional ESI-MS. In this approach, ion peaks due to the addition of nine water molecules were identified at a spray temperature of 48 degrees C. This result showed good agreement with that inferred by the combinational analysis of NMR and X-ray crystallography, indicating that CSI-MS is capable of rapidly providing reliable information to characterize the number of water molecules bound to a macromolecule.
The metal-induced self-assembly of a resorcin[4]arene derivative 1 that has four pyridine units as pendent groups and two equivalents of [M(dppp)(OTf)(2)] (M=Pd, Pt) results in a dynamic equilibrium between an interclipped supramolecular capsule 3 and an intraclipped bowl 4 in nitromethane, although the interclipped capsule 3 is formed as a sole adduct in chloroform/methanol and the intraclipped bowl 4 is formed exclusively in an aqueous phase. This demonstrates how metal-induced self-assembly can be tuned by subtle changes in the solvent system. The coexistence of the two structures in nitromethane was characterized by NMR spectroscopy and coldspray ionization mass spectrometry (CSI-MS). The crystal structure of the interclipped capsule 3 b, which is composed of two units of ligand 1 and four Pt(II) ions, reveals the capsule cavity to have nanoscale dimensions of 15x20 A. NMR spectra show that the dynamic equilibrium between 3 and 4 is dependent on concentration and temperature. Temperature-dependent (1)H NMR spectroscopy was carried out from 273 to 343 K to verify the thermodynamic parameters that control the dynamic equilibrium process; the conversion from the interclipped supramolecular capsule 3 a to the intraclipped bowl 4 a is entropically favored and enthalpically disfavored. The rotational barrier of the restricted rotation of pyridine units in the intraclipped bowl 4 was determined by line-shape analysis.
Reaction of gamma-silyl-beta,gamma-epoxybutanenitrile with a base generates an alpha-nitrile carbanion derivative of 4-siloxybut-3-enenitrile, which undergoes reaction with bis-electrophiles such as 1,omega-dihaloalkanes, omega-bromo-alpha,beta-unsaturated esters, and bisenoates to provide highly functionalized carbocycles.
Selective formation of a homo- or hetero-cavitand cage via metal-coordination, by using tetra(4-pyridyl)-cavitand (1), tetrakis(4-pyridylethynyl)-cavitand (2), or tetrakis(4-cyanophenyl)-cavitand (3) as deep cavitand ligands and Pd(dppp)(OTf)2 (4) as a connector, has been investigated by 1H NMR and CSI-MS. When the cavitand and 4 were mixed in CDCl3 in a 2:4 molar ratio, 1 gave a complicated mixture, whereas 2 or 3 formed a homo-cavitand cage {2(2).4[Pd(dppp)]}8+.8(TfO-) (5) or {2(3).4[Pd(dppp)]}8+.8(TfO-) (6), respectively, as a single species. In a 1:1:4 mixture of 2, 3, and 4, homo-cavitand cages 5 and 6 were observed in a 1:1 ratio. In marked contrast, a mixture of 1, 3, and 4 in a 1:1:4 ratio was exclusively self-assembled into a hetero-cavitand cage {1.3.4[Pd(dppp)]}8+.8(TfO-) (7). The selectivity for the self-assembly of the homo- or hetero-cavitand cage via metal coordination would arise from a combination of factors such as coordination ability and steric demand of cavitand ligands.
Explore the source record for details and available documents.
Several members of the P450 family, including cytochrome P450 1B1 (CYP1B1), can convert tobacco smoke (TS) procarcinogens, including benzo[a]pyrene (B[a]P), to carcinogenic intermediates. In this study we investigated the effects of TS condensate and B[a]P on the expression of CYP1B1 in vitro and in vivo. CYP1B1 mRNA and protein were induced by both TS condensate and B[a]P in cell lines derived from the human aerodigestive tract. Treatment with TS condensate stimulated binding of the aryl hydrocarbon receptor (AhR) to an oligonucleotide containing a canonical xenobiotic response element (XRE) site and induced XRE-luciferase activity. These findings are consistent with prior evidence that polycyclic aromatic hydrocarbons, known ligands of the AhR, stimulate CYP1B1 transcription by an XRE-dependent mechanism. To determine whether these in vitro findings applied in vivo, both murine and human studies were carried out. Short-term exposure to TS induced CYP1B1 in the tongue, esophagus, lung and colon of experimental mice. In contrast, CYP1B1 was not induced by TS in the aorta of these mice. Levels of CYP1B1 mRNA were also elevated in the bronchial mucosa of human tobacco smokers versus never smokers (P < 0.05). Taken together, these results support a role for CYP1B1 in TS-induced carcinogenesis in the aerodigestive tract.
A self-assembled dimeric macrocycle between 4,4'-bis(4-pyridylmethoxy)biphenyl (L) and (en)Pd(NO(3))(2) was constructed, and its interactions with cyclodextrins of different cavity size resulted in the formation of [2]catenane and [2]pseudorotaxane systems, respectively. The structures were identified by 1D and 2D NMR spectroscopy and cold spray ionization mass (CSI-MS) spectrometry.
Three analogues of RA-VII (1), an antitumor bicyclic hexapeptide from Rubia plants, were synthesized. Three analogues, [Gly-1]RA-VII (4), [Gly-2]RA-VII (5), and [Gly-4]RA-VII (6), in which one of the three alanine residues in 1 was replaced by a glycine residue, were prepared by linking of the cycloisodityrosine unit, obtained by degradation of 1, to three different glycine-containing tetrapeptides followed by macrocyclization. Of these three analogues, analogue 4 showed the highest cytotoxic activity. The NMR study revealed that in solution the conformer structures and their ratios of analogue 4 were very similar to those of natural peptide 1, suggesting that the methyl groups at Ala-2 and Ala-4 should be essential for producing the bioactive conformation, whereas that at D-Ala-1 is not essential.
Phase-selective photochemical reaction of 2-pyridone derivatives was examined. Irradiation of 1 in benzene mainly gave rearrangement products 2. However, intermolecular [4 + 4] photocycloaddition proceeded quantitatively in the solid state, affording photodimers 3. An effective pi-pi stacking and dipole-dipole interaction between two pyridone moieties might play important roles in an effective arrangement of 1 for photodimerization in their crystal structures. [reaction: see text]
A novel approach to the noncovalent synthesis of molecular necklaces successfully led to the first quantitative self-assembly of a molecular necklace [6]MN, in which five small rings are threaded on a large ring, from 10 components. Our strategy involves the host-guest complex formation between the molecular host cucurbit[8]uril (CB[8]) and a guest molecule in which an electron donor and an electron acceptor unit are connected by a rigid linker with a proper angle, to form a cyclic oligomer through the host-stabilized intermolecular charge-transfer (CT) complex formation. In the structure of the molecular necklace [6]MN, five molecules of the guest form a cyclic framework by the intermolecular CT interactions, on which five CB[8] molecules are threaded with an arrangement reminiscent of a five-fold propeller. The molecular necklace measures approximately 3.7 nm in diameter and approximately 1.8 nm in thickness.
A method was developed for synthesizing alpha,alpha-disubstituted glycine residues bearing a large (more than 15-membered) hydrophobic ring. The ring-closing metathesis reactions of the dialkenylated malonate precursors proceed efficiently, particularly when long methylene chains tether both terminal olefin groups. Surprisingly, the amino groups of these alpha,alpha-disubstituted glycines are inert to conventional protective reactions (e.g., N-tert-butoxycarbonyl (Boc) protection: Boc(2)O/4-dimethylaminopyridine (DMAP)/CH(2)Cl(2); N-benzyloxycarbonyl (Z) protection: Z-Cl/DMAP/CH(2)Cl(2)). Curtius rearrangement of the carboxylic acid functionality of the malonate derivative after ring-closing metathesis leads to formation of an amine functionality and can be catalyzed by diphenylphosphoryl azide. However, only the intermediate isocyanates can be isolated, even in the presence of alcohols such as benzyl alcohol. The isocyanates obtained by Curtius rearrangement in an aprotic solvent (benzene) were isolated in high yields and treated with 9-fluorenylmethanol in a high-boiling-point solvent (toluene) under reflux to give the N-9-fluorenylmethoxycarbonyl (Fmoc)-protected aminomalonate derivatives in high yield. These hydrophobic amino acids can be incorporated into a peptide by Fmoc solid-phase peptide synthesis and the acid fluoride activation method. The stability of the monomeric alpha-helical structure of a 17-amino-acid peptide was enhanced by replacement of two alanine residues with two hydrophobic amino acid residues bearing a cyclic 18-membered ring. The results of sedimentation equilibrium studies suggested that the peptide assembles into hexamers in the presence of 100 mM NaCl.
Two unidentified arsenic metabolites were detected in the liver of rats on a gel filtration column by HPLC inductively coupled argon plasma mass spectrometry after an injection of dimethylarsinic (DMA(V)), dimethylarsinous (DMA(III)), monomethylarsonic (MMA(V)), or monomethylarsonous (MMA(III)) acid. The same arsenicals were also produced in vitro by incubation of DMA(III) in the liver supernatant but not by DMA(V). The two arsenic metabolites eluted at the same retention times as those of the two arsenicals prepared by reaction of DMA(V) with either thiosulfate plus disulfite or hydrogen sulfide or sodium sulfide plus sulfuric acid. The faster and slower eluting products on a gel filtration column were assigned as dimethyldithioarsinic acid (dimethylarsinodithioic acid) (DMTA(V)) and dimethylthioarsinous acid (DMTA(III)) from mass spectrometric data at m/z = 170 and 138 by electrospray ionization mass spectrometry with negative and positive ion modes, respectively. They were prepared selectively by reacting DMA(V) with hydrogen sulfide or sodium sulfide plus sulfuric acid under different reaction conditions. DMA(III) but not DMA(V) was transformed to DMTA(III) and DMTA(V) in the presence of sodium sulfide in vitro, suggesting that DMA(V) is reduced to DMA(III) with hydrogen sulfide, thiolated to DMTA(III), and then further thiolated oxidatively to DMTA(V). Metabolically, it is assumed that DMA(III) is transformed to DMTA(III) in the presence of sulfide ions, and then, DMTA(III) is oxidatively thiolated to DMTA(V). As the chemical species produced by reduction with the Reay and Asher method are DMTA(III) and DMTA(V), and different from DMA(III), the studies carried out with DMA(III) with the Reay and Asher method have to be reexamined.
We prepared and characterized a grinding-induced equimolar complex of thiourea with ethenzamide. When thiourea and ethenzamide were co-ground at a molar ratio of 3 : 1, new powder X-ray diffraction (PXRD) peaks were observed in addition to PXRD peaks of thiourea crystals. The optimum stoichiometry of the new structure was confirmed as 1 : 1 mol/mol. Effect of grinding time on the thiourea-ethenzamide equimolar complex formation was investigated by using PXRD, differential scanning calorimetry and Fourier transform infrared spectroscopy. The equimolar crystal structure was confirmed by X-ray diffraction measurements of the single crystal which was recrystallized from ethanol. It was found that the intermolecular hydrogen bond formations between thiourea and ethenzamide molecules contributed to the equimolar complex formation. The complex formation was not observed in the cases where benzamide, salicylamide or 3-ethoxybenzamide was co-ground with thiourea. 2-Alcoxyl benzamide structures should be required for the grinding-induced equimolar complex formation with thiourea.