Interaction of Ferrocene Moieties Across a Square Pt₄ Unit: Synthesis, Characterization, and Electrochemical Properties of Carboxylate-Bridged Bimetallic Pt₄Fe_<i>n</i> (<i>n</i> = 2, 3, and 4) Complexes

Four types of square Pt₄ complexes bearing two or more ferrocenecarboxylate ligands[Pt₄(μ-OCOCH₃)₄(μ-OCOC₅H₄FeCp)₄] (<b>6</b>); [Pt₄(μ-OCOCH₃)₄(μ-OCOC₅H₄FeCp)₃(μ-ArNCHNAr)], where ArNCHNAr = <i>N</i>,<i>N′</i>-diarylformamidinate) (<b>7</b>); <i>trans</i>-[Pt₄(μ-OCOCH₃)₄(μ-OCOC₅H₄FeCp)₂(μ-ArNCHNAr)₂] (<b>8</b>); and <i>cis</i>-[Pt₄(μ-OCOCH₃)₄(μ-OCOC₅H₄FeCp)₂(κ⁴-<i>N</i>₄-DArBp)₂], where DArBp = 1,3-bis(benzamidinato)propane (<b>9</b>)were successfully prepared via reactions of [FeCp(η⁵-C₅H₄COOH)] (<b>5</b>) with the corresponding square Pt₄ complexes, which have labile <i>in-plane</i> acetate ligands. The newly prepared Pt₄ complexes (<b>6</b>–<b>9</b>) with ferrocene moieties as pendants were characterized by nuclear magnetic resonance (NMR) spectroscopy, mass spectroscopy (MS), combustion analyses, and single-crystal X-ray analysis for <b>6</b>, some of the <i>trans</i>-Pt₄Fe₂ <b>8</b>, and the <i>cis</i>-Pt₄Fe₂ complexes <b>9</b>. Weak interactions between two ferrocene moieties across the Pt₄ core, providing Δ<i>E</i>_1/2 values and <i>K</i>_c constants, were revealed electrochemically, using cyclic and differential-pulse voltammetry in dichloromethane containing [^<i>n</i>Bu₄N][BAr^F₄] (where Ar^F = C₆H₃(CF₃)₂-3,5), which was a better supporting electrolyte for such an interaction than [^<i>n</i>Bu₄N][PF₆]

Interaction of Ferrocene Moieties Across a Square Pt₄ Unit: Synthesis, Characterization, and Electrochemical Properties of Carboxylate-Bridged Bimetallic Pt₄Fe_<i>n</i> (<i>n</i> = 2, 3, and 4) Complexes

Four types of square Pt₄ complexes bearing two or more ferrocenecarboxylate ligands[Pt₄(μ-OCOCH₃)₄(μ-OCOC₅H₄FeCp)₄] (<b>6</b>); [Pt₄(μ-OCOCH₃)₄(μ-OCOC₅H₄FeCp)₃(μ-ArNCHNAr)], where ArNCHNAr = <i>N</i>,<i>N′</i>-diarylformamidinate) (<b>7</b>); <i>trans</i>-[Pt₄(μ-OCOCH₃)₄(μ-OCOC₅H₄FeCp)₂(μ-ArNCHNAr)₂] (<b>8</b>); and <i>cis</i>-[Pt₄(μ-OCOCH₃)₄(μ-OCOC₅H₄FeCp)₂(κ⁴-<i>N</i>₄-DArBp)₂], where DArBp = 1,3-bis(benzamidinato)propane (<b>9</b>)were successfully prepared via reactions of [FeCp(η⁵-C₅H₄COOH)] (<b>5</b>) with the corresponding square Pt₄ complexes, which have labile <i>in-plane</i> acetate ligands. The newly prepared Pt₄ complexes (<b>6</b>–<b>9</b>) with ferrocene moieties as pendants were characterized by nuclear magnetic resonance (NMR) spectroscopy, mass spectroscopy (MS), combustion analyses, and single-crystal X-ray analysis for <b>6</b>, some of the <i>trans</i>-Pt₄Fe₂ <b>8</b>, and the <i>cis</i>-Pt₄Fe₂ complexes <b>9</b>. Weak interactions between two ferrocene moieties across the Pt₄ core, providing Δ<i>E</i>_1/2 values and <i>K</i>_c constants, were revealed electrochemically, using cyclic and differential-pulse voltammetry in dichloromethane containing [^<i>n</i>Bu₄N][BAr^F₄] (where Ar^F = C₆H₃(CF₃)₂-3,5), which was a better supporting electrolyte for such an interaction than [^<i>n</i>Bu₄N][PF₆]

Enantioselective Synthesis of Pyrrolidine-, Piperidine-, and Azepane-Type <i>N</i>-Heterocycles with α-Alkenyl Substitution: The CpRu-Catalyzed Dehydrative Intramolecular <i>N</i>-Allylation Approach

A cationic CpRu complex of chiral picolinic acid derivatives [(<i>R</i>)- or (<i>S</i>)-Cl-Naph-PyCOOCH₂CHCH₂] catalyzes asymmetric intramolecular dehydrative <i>N</i>-allylation of <i>N</i>-substituted ω-amino- and -aminocarbonyl allylic alcohols with a substrate/catalyst ratio of up to 2000 to give α-alkenyl pyrrolidine-, piperidine-, and azepane-type <i>N</i>-heterocycles with an enantiomer ratio of up to >99:1. The wide range of applicable <i>N</i>-substitutions, including Boc, Cbz, Ac, Bz, acryloyl, crotonoyl, formyl, and Ts, significantly facilitates further manipulation toward natural product synthesis

Enantioselective Synthesis of Pyrrolidine-, Piperidine-, and Azepane-Type <i>N</i>-Heterocycles with α-Alkenyl Substitution: The CpRu-Catalyzed Dehydrative Intramolecular <i>N</i>-Allylation Approach

A cationic CpRu complex of chiral picolinic acid derivatives [(<i>R</i>)- or (<i>S</i>)-Cl-Naph-PyCOOCH₂CHCH₂] catalyzes asymmetric intramolecular dehydrative <i>N</i>-allylation of <i>N</i>-substituted ω-amino- and -aminocarbonyl allylic alcohols with a substrate/catalyst ratio of up to 2000 to give α-alkenyl pyrrolidine-, piperidine-, and azepane-type <i>N</i>-heterocycles with an enantiomer ratio of up to >99:1. The wide range of applicable <i>N</i>-substitutions, including Boc, Cbz, Ac, Bz, acryloyl, crotonoyl, formyl, and Ts, significantly facilitates further manipulation toward natural product synthesis

Intramolecular Tsuji–Trost-type Allylation of Carboxylic Acids: Asymmetric Synthesis of Highly π‑Allyl Donative Lactones

Tsuji–Trost-type asymmetric allylation of carboxylic acids has been realized by using a cationic CpRu complex with an axially chiral picolinic acid-type ligand (Cl-Naph-PyCOOH: naph = naphthyl, py = pyridine). The carboxylic acid and allylic alcohol intramolecularly condense by the liberation of water without stoichiometric activation of either nucleophile or electrophile part, thereby attaining high atom- and step-economy, and low <i>E</i> factor. This success can be ascribed to the higher reactivity of allylic alcohols as compared with the allyl ester products in soft Ru/hard Brønstead acid combined catalysis, which can function under slightly acidic conditions unlike the traditional Pd-catalyzed system. Detailed analysis of the stereochemical outcome of the reaction using an enantiomerically enriched D-labeled substrate provides an intriguing view of enantioselection

Modular Construction of Protected 1,2/1,3-Diols, -Amino Alcohols, and -Diamines via Catalytic Asymmetric Dehydrative Allylation: An Application to Synthesis of Sphingosine

A new enantioselective catalysis has been developed for the one-step construction of methylene-bridged chiral modules of 1,2- and 1,3-OH and/or NH function(s) from δ- or λ-OH/NHBoc-substituted allylic alcohols and “H₂CO”/“H₂CNBoc”. A protonic nucleophile, either in situ-generated CH₂OH or CH₂NHBoc, is intramolecularly allylated to furnish eight possible 1,2- or 1,3-O,O, -O,N, -N,O, and -N,N chiral modules equipped with an ethenyl group in high yields and enantioselectivities. The utility of this method has been demonstrated in the five-step synthesis of sphingosine

Mechanism of Asymmetric Hydrogenation of Aromatic Ketones Catalyzed by a Combined System of Ru(π-CH₂C(CH₃)CH₂)₂(cod) and the Chiral sp²N/sp³NH Hybrid Linear N4 Ligand Ph-BINAN-H-Py

The combination of a Goodwin–Lions-type chiral N4 ligand, (<i>R</i>)-Ph-BINAN-H-Py ((<i>R</i>)-3,3′-diphenyl-<i>N</i>²,<i>N</i>^2′-bis­((pyridin-2-yl)­methyl)-1,1′-binaphthyl-2,2′-diamine; <b>L</b>), with Ru­(π-CH₂C­(CH₃)­CH₂)₂(cod) (<b>A</b>) (cod = 1,5-cyclooctadiene) catalyzes the hydrogenation of acetophenone (<b>AP</b>) to (<i>R</i>)-1-phenylethanol (<b>PE</b>) with a high enantiomer ratio (er). Almost no Ru complex forms, with <b>A</b> and <b>L</b> remaining intact throughout the reaction while generating <b>PE</b> quantitatively according to [<b>PE</b>] = <i>k</i>_obs<i>t</i>². An infinitesimal amount of reactive and unstable RuH₂<b>L</b> (<b>B</b>) with <i>C</i>₂-Λ-<i>cis</i>-α stereochemistry is very slowly and irreversibly generated from <b>A</b> by the action of H₂ and <b>L</b>, which rapidly catalyzes the hydrogenation of <b>AP</b> via Noyori’s donor–acceptor bifunctional mechanism. A CH-π-stabilized <i>Si</i>-face selective transition state, <b>C</b>_{<i><b>Si</b></i>}, gives (<i>R</i>)-<b>PE</b> together with an intermediary Ru amide, <b>D</b>, which is inhibited predominantly by formation of the Ru enolate of <b>AP</b>. The rate-determining hydrogenolysis of <b>D</b> completes the cycle. The time-squared term relates both to the preliminary step before the cycle and to the cycle itself, with a highly unusual eight-order difference in the generation and turnover frequency of <b>B</b>. This mechanism is fully supported by a series of experiments including a detailed kinetic study, rate law analysis, simulation of <i>t</i>/[<b>PE</b>] curves with fitting to the experimental observations at the initial reaction stage, X-ray crystallographic analyses of <b>B</b>-related octahedral metal complexes, and Hammett plot analyses of electronically different substrates and ligands in their enantioselectivities

Differences of histone methylation status depending on Twist1 expression in murine and human GC cells.

<p>(A) Histone methylation status in Twist1 expression-positive cells (MDGC-7 and MDGC-9) and -negative cells (MDGC-1 and MDGC-3). ChIP assay was conducted using H3K4me3, H3K9me3, H3K27me3 and H3K36me2 antibodies. The five ChIP regions (CP1.3k, CP1, CE1-1, CE1-2 and CE2) analyzed are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145630#pone.0145630.g002" target="_blank">Fig 2A</a>. Input DNA samples were used as internal controls. (B) Semi-quantitative ChIP analyses of histone H3K4me3 and H3K9me3 enrichment. ChIP intensities were analyzed using Image J 1.47v software, and then ChIP/Input was calculated. Active histone mark H3K4me3 was enriched in Twist1 expression-positive cells, but inactive histone mark H3K9me3 was enriched in Twist1 expression-negative cells. (C) The relationship between histone and CGI methylation in MDGC cells. MDGC-1 and MDGC-3 cells were treated with 5-aza-dC, and the histone methylation status of their H3K4me3 and H3K9me3 was examined by ChIP assay. The H3K4me3 levels were increased in these 5-aza-dC-treated cells compared in untreated controls (Fig 4A), as shown by triangles. (D) Semi-quantitative ChIP analysis of H3K4me and H3K9me3 in human GC cells. The regions (CP1, CE1-2) analyzed are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145630#pone.0145630.g002" target="_blank">Fig 2C</a>. Similar to the data for mouse <i>Twist1</i> (Fig 4B), the H3K4me3 and H3K9me3 levels were enriched in MKN45 and KATO-III cells, respectively. The average (column) ± S.D (bar) for three independent agarose gel electrophorese in different experiments is indicated (**P<0.01).</p

Twist1 expression in murine and human GC cell lines.

<p>(A) RT-PCR analysis of <i>Twist1</i> mRNA expression in five mouse GC cell lines MDGC-1, MDGC-3, MDGC-7, MDGC-8 and MDGC-9) from DCKO mice. Mouse <i>Gapdh</i> was used as an internal control. (B) Expression of Twist1 protein in MDGC cells by Western blot. α-tubulin was used as an internal control. (C and D) Effects of a DNA demethylation agent in MDGC cells. After treatment with 5-aza-dC, <i>Twist1</i> expression was up-regulated at the mRNA (C) and protein levels (D) in Twist1 expression-negative MDGC-1 and MDGC-3 cells, but not in Twist1 expression-positive MDGC-9 cells. M, mock; A, 5-aza-dC. (E) RT-PCR analysis of <i>Twist1</i> mRNA expression in human GC cell lines (KATO-III, GCIY, AGS, MKN74, MKN7, MKN45, NUGC4 and HSC60) (left). <i>Twist1</i> expression was up-regulated at the mRNA level in KATO-III and GCIY cells after 5-aza-dC treatment (right). Human <i>GAPDH</i> was used as an internal control. (F) qRT-PCR analysis of <i>Twist1</i> mRNA expression in MDGC-9, MKN7 and MKN45 cells with and without 5-aza-dC treatment (**P<0.01).</p

The expression and methylation status of <i>Twist1</i> during cancer progression.

<p>(A) Representative results of nested MSP analysis of <i>Twist1</i> in DGCs from DCKO mice and a corresponding non-cancerous gastric mucosa (lane N). The regions (E1-2) analyzed are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145630#pone.0145630.g002" target="_blank">Fig 2A</a>. U: unmethylated allele; M: methylated allele. (B) Representative immunohistochemical staining of Twist1 protein in DGC tissues from DCKO mice. (i) Strong nuclear staining of Twist1 protein in a GC without methylation. (ii) Negative Twist1 protein expression in a GC with methylation. Original magnification, x400. (C) Summary of <i>Twist1</i> methylation and expression in primary DGCs. <i>Twist1</i> was methylated in 9 of 18 GCs, as indicated by M. The intensity of Twist1 staining was scored as–(negative), + (weak) and ++ (moderate to strong). Mouse GCs were divided into two groups, intramucosal and invasive GCs according to the criteria of human GC established by the Japanese Gastric Cancer Association [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145630#pone.0145630.ref053" target="_blank">53</a>].</p