Synthesis and Reactivity of the Fluoro Complex <i>trans</i>-[Pd(F)(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂]: C–F Bond Formation and Catalytic C–F Bond Activation Reactions

The reaction of [Pd­(Me)₂(tmeda)] (tmeda = <i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>′-tetramethylethylendiamine) with the phosphine ^<i>i</i>Pr₂PCH₂CH₂OCH₃ resulted in the formation of the palladium(0) complex [Pd­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>1</b>). Treatment of <b>1</b> with pentafluoropyridine at room temperature yielded the C–F activation product <i>trans</i>-[Pd­(F)­(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>2</b>). The triflato and bromo complexes <i>trans</i>-[Pd­(OTf)­(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>4</b>) and <i>trans</i>-[Pd­(Br)­(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>5</b>) could be prepared on reaction of complex <b>2</b> with EtOTf or 3-bromopropene, respectively. Treatment of <b>2</b> with Me₃SiCl or HBpin (HBpin = 4,4,5,5-tetramethyl-1,3,2-dioxaborolane, pinacolborane) effects the formation of <i>trans</i>-[Pd­(Cl)­(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>6</b>) and <i>trans</i>-[Pd­(H)­(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>7</b>). In catalytic experiments pentafluoropyridine could be converted into the 4-aryl-tetrafluoropyridines (<b>8</b>, aryl = Ph; <b>9</b>, aryl = Tol) and into 2,3,5,6-tetrafluoropyridine in the presence of the boronic acids PhB­(OH)₂, TolB­(OH)₂, or HBpin when 5 mol % of <b>2</b> is employed as catalyst

Synthesis and Reactivity of the Fluoro Complex <i>trans</i>-[Pd(F)(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂]: C–F Bond Formation and Catalytic C–F Bond Activation Reactions

The reaction of [Pd­(Me)₂(tmeda)] (tmeda = <i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>′-tetramethylethylendiamine) with the phosphine ^<i>i</i>Pr₂PCH₂CH₂OCH₃ resulted in the formation of the palladium(0) complex [Pd­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>1</b>). Treatment of <b>1</b> with pentafluoropyridine at room temperature yielded the C–F activation product <i>trans</i>-[Pd­(F)­(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>2</b>). The triflato and bromo complexes <i>trans</i>-[Pd­(OTf)­(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>4</b>) and <i>trans</i>-[Pd­(Br)­(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>5</b>) could be prepared on reaction of complex <b>2</b> with EtOTf or 3-bromopropene, respectively. Treatment of <b>2</b> with Me₃SiCl or HBpin (HBpin = 4,4,5,5-tetramethyl-1,3,2-dioxaborolane, pinacolborane) effects the formation of <i>trans</i>-[Pd­(Cl)­(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>6</b>) and <i>trans</i>-[Pd­(H)­(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>7</b>). In catalytic experiments pentafluoropyridine could be converted into the 4-aryl-tetrafluoropyridines (<b>8</b>, aryl = Ph; <b>9</b>, aryl = Tol) and into 2,3,5,6-tetrafluoropyridine in the presence of the boronic acids PhB­(OH)₂, TolB­(OH)₂, or HBpin when 5 mol % of <b>2</b> is employed as catalyst

Synthesis and Reactivity of the Fluoro Complex <i>trans</i>-[Pd(F)(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂]: C–F Bond Formation and Catalytic C–F Bond Activation Reactions

The reaction of [Pd­(Me)₂(tmeda)] (tmeda = <i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>′-tetramethylethylendiamine) with the phosphine ^<i>i</i>Pr₂PCH₂CH₂OCH₃ resulted in the formation of the palladium(0) complex [Pd­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>1</b>). Treatment of <b>1</b> with pentafluoropyridine at room temperature yielded the C–F activation product <i>trans</i>-[Pd­(F)­(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>2</b>). The triflato and bromo complexes <i>trans</i>-[Pd­(OTf)­(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>4</b>) and <i>trans</i>-[Pd­(Br)­(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>5</b>) could be prepared on reaction of complex <b>2</b> with EtOTf or 3-bromopropene, respectively. Treatment of <b>2</b> with Me₃SiCl or HBpin (HBpin = 4,4,5,5-tetramethyl-1,3,2-dioxaborolane, pinacolborane) effects the formation of <i>trans</i>-[Pd­(Cl)­(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>6</b>) and <i>trans</i>-[Pd­(H)­(4-C₅NF₄)­(^<i>i</i>Pr₂PCH₂CH₂OCH₃)₂] (<b>7</b>). In catalytic experiments pentafluoropyridine could be converted into the 4-aryl-tetrafluoropyridines (<b>8</b>, aryl = Ph; <b>9</b>, aryl = Tol) and into 2,3,5,6-tetrafluoropyridine in the presence of the boronic acids PhB­(OH)₂, TolB­(OH)₂, or HBpin when 5 mol % of <b>2</b> is employed as catalyst

Zinc Complexes with the N‑Donor-Functionalized Cyclopentadienyl Ligand C₅Me₄(CH₂)₂NMe₂

The amino-functionalized zincocene [ZnCp^N₂] (<b>4</b>; Cp^N = C₅Me₄(CH₂)₂NMe₂), which is the first mononuclear zincocene with two donor-functionalized cyclopentadienyl ligands, was prepared through treatment of KCp^N with ZnCl₂ in a 2/1 ratio. X-ray crystallography reveals the chelating binding mode of each Cp^N ligand via an η¹-coordinated Cp ring and the amino group. The structural dynamics of <b>4</b> in solution were examined by variable-temperature ¹H NMR spectroscopy, and decoalescence of the NMR signals was found at low temperatures. Reacting <b>4</b> with [ZnR₂] (R = Et, Cp*) yields the monocyclopentadienyl and mixed-ring donor-functionalized complexes [ZnEtCp^N] (<b>5</b>) and [ZnCp*Cp^N] (<b>6</b>). In contrast to the reaction of KCp^N with ZnCl₂ in a 2/1 ratio, which yields the zincocene <b>4</b>, the reaction in a 1/1 ratio results exclusively in the formation of the chlorido-bridged dimer [Zn­(μ-Cl)­Cp^N]₂ (<b>7</b>). This compound is comparable to [Zn­(μ-Cl)­Cp*­(THF)]₂ (<b>8</b>), which crystallizes from a THF solution of equimolar amounts of [ZnCp*₂] (<b>1</b>) and ZnCl₂

C–H and C–F Bond Activations at a Rhodium(I) Boryl Complex: Reaction Steps for the Catalytic Borylation of Fluorinated Aromatics

Treatment of the rhodium­(I) boryl complex [Rh­(Bpin)­(PEt₃)₃] (<b>1</b>, pin = pinacolato = O₂C₂Me₄) with pentafluorobenzene, 1,3,5-trifluorobenzene, 1,3-difluorobenzene, or 3,5-difluoropyridine led to C–H activation reactions to give the aryl complexes [Rh­(C₆F₅)­(PEt₃)₃] (<b>4</b>), [Rh­(2,4,6-C₆F₃H₂)­(PEt₃)₃] (<b>5</b>), [Rh­(2,6-C₆F₂H₃)­(PEt₃)₃] (<b>6</b>), and [Rh­{4-(3,5-C₅NF₂H₂)}­(PEt₃)₃] (<b>8</b>). For <b>5</b>, <b>6</b>, and <b>8</b> consecutive reactions with <i>in situ</i> generated HBpin occurred to yield [Rh­(H)­(PEt₃)₃] (<b>7</b>) and boronic esters. The boryl complex <b>1</b> gave with hexafluorobenzene or perfluorotoluene the C–F activation products [Rh­(C₆F₅)­(PEt₃)₃] (<b>4</b>) and [Rh­(4-C₆F₄CF₃)­(PEt₃)₃] (<b>9</b>), respectively. The complexes <b>5</b>, <b>6</b>, and <b>9</b> react with B₂pin₂ to yield <b>1</b> and boronic ester derivatives. On the basis of these stoichiometric reactions catalytic C–H and C–F borylation reactions using <b>1</b> or <b>7</b> were developed to generate 2-Bpin-1,3,5-C₆F₃H₂, 2-Bpin-1,3-C₆F₂H₃, and 4-Bpin-C₆F₄CF₃ from 1,3,5-trifluorobenzene, 1,3-difluorobenzene, or perfluorotoluene and B₂pin₂. On treatment of pentafluoropyridine with B₂pin₂ in the presence of <b>1</b> or <b>7</b> as catalyst 2-Bpin-C₅NF₄ was synthesized by C–F borylation at the 2-position. Using 2,3,5,6-tetrafluoropyridine, B₂pin₂, and catalytic amounts of <b>7</b> led to a C–H borylation reaction at the 4-position. 4-Bpin-C₅NF₄ can also be prepared by the reaction of 2,3,5,6-tetrafluoropyridine with stoichiometric amounts of HBpin or by the reaction of pentafluoropyridine with an excess of HBpin in the presence of <b>7</b>, whereas the reaction of pentafluoropyridine with stoichiometric amounts of HBpin and 5 mol % <b>7</b> resulted in the formation of 2,3,5,6-tetrafluoropyridine via hydrodefluorination reaction at the 4-position. This regioselectivity contrasts the borylation of pentafluoropyridine at the 2-position with <b>1</b> as catalyst. Overall, the obtained fluorinated aryl boronic ester derivatives might serve as versatile building blocks

Neutral and Cationic Zinc Complexes with N- and S‑Donor-Functionalized Cyclopentadienyl Ligands

The synthesis of neutral and cationic zinc cyclopentadienyl (Cp) complexes with amino and thio donor groups that are attached to the Cp ring via a side chain is reported. The amino-functionalized zincocene [ZnCp^3N₂] (<b>3</b>; Cp^3N = C₅Me₄(CH₂)₃NMe₂) was prepared in a salt metathesis reaction from KCp^3N and ZnCl₂. In the solid-state structure of <b>3</b>, which was determined by single-crystal X-ray diffraction, one of the Cp^3N ligands is coordinated as a chelating ligand through a ring carbon atom and through the amino group, whereas the other Cp^3N ligand is bound in a monodentate mode through the Cp ring only. A reaction of <b>3</b> with ZnEt₂, [ZnCp*₂] (Cp* = C₅Me₅), and [ZnCp^2N₂] (<b>2</b>; Cp^2N = C₅Me₄(CH₂)₂NMe₂) gave the heteroleptic complexes [ZnEtCp^3N] (<b>4</b>), [ZnCp*Cp^3N] (<b>5</b>), and [ZnCp^3NCp^2N] (<b>6</b>), respectively. The incorporation of a second amino group in the same side chain led to the formation of the mononuclear zinc chlorido complex [ZnClCp^tmeda] (<b>7</b>; Cp^tmeda = C₅Me₄(CH₂)₂NMe­(CH₂)₂NMe₂), in which the Cp^tmeda ligand is bound in a tridentate coordination mode. In addition, the thio-functionalized zincocene [ZnCp^2S₂] (<b>8</b>; Cp^2S = C₅Me₄(CH₂)₂SMe) was obtained and shown to exhibit an intramolecular coordination by the sulfur atoms. Starting from the neutral complexes <b>2</b>, <b>3</b>, and <b>8</b>, the cationic compounds [ZnCp^D(py)₂]⁺[BAr^F₄]⁻ (Cp^D = Cp^2N (<b>9</b>), Cp^3N (<b>10</b>), Cp^2S (<b>11</b>); py = pyridine; BAr^F₄ = B­{3,5-(CF₃)₂C₆H₃}₄) were obtained either by protonation or upon reaction with an electrophile in the presence of pyridine. In these cationic complexes the highly electrophilic zinc center is stabilized by intramolecular coordination through the donor groups

Zinc Complexes with the N‑Donor-Functionalized Cyclopentadienyl Ligand C₅Me₄(CH₂)₂NMe₂

The amino-functionalized zincocene [ZnCp^N₂] (<b>4</b>; Cp^N = C₅Me₄(CH₂)₂NMe₂), which is the first mononuclear zincocene with two donor-functionalized cyclopentadienyl ligands, was prepared through treatment of KCp^N with ZnCl₂ in a 2/1 ratio. X-ray crystallography reveals the chelating binding mode of each Cp^N ligand via an η¹-coordinated Cp ring and the amino group. The structural dynamics of <b>4</b> in solution were examined by variable-temperature ¹H NMR spectroscopy, and decoalescence of the NMR signals was found at low temperatures. Reacting <b>4</b> with [ZnR₂] (R = Et, Cp*) yields the monocyclopentadienyl and mixed-ring donor-functionalized complexes [ZnEtCp^N] (<b>5</b>) and [ZnCp*Cp^N] (<b>6</b>). In contrast to the reaction of KCp^N with ZnCl₂ in a 2/1 ratio, which yields the zincocene <b>4</b>, the reaction in a 1/1 ratio results exclusively in the formation of the chlorido-bridged dimer [Zn­(μ-Cl)­Cp^N]₂ (<b>7</b>). This compound is comparable to [Zn­(μ-Cl)­Cp*­(THF)]₂ (<b>8</b>), which crystallizes from a THF solution of equimolar amounts of [ZnCp*₂] (<b>1</b>) and ZnCl₂

ResA³: A Web Tool for Resampling Analysis of Arbitrary Annotations

<div><p>Resampling algorithms provide an empirical, non-parametric approach to determine the statistical significance of annotations in different experimental settings. ResA³ (<u>Res</u>ampling <u>A</u>nalysis of <u>A</u>rbitrary <u>A</u>nnotations, short: ResA) is a novel tool to facilitate the analysis of enrichment and regulation of annotations deposited in various online resources such as KEGG, Gene Ontology and Pfam or any kind of classification. Results are presented in readily accessible navigable table views together with relevant information for statistical inference. The tool is able to analyze multiple types of annotations in a single run and includes a Gene Ontology annotation feature. We successfully tested ResA using a dataset obtained by measuring incorporation rates of stable isotopes into proteins in intact animals. ResA complements existing tools and will help to evaluate the increasing number of large-scale transcriptomics and proteomics datasets (resa.mpi-bn.mpg.de).</p> </div

Resulting <i>p</i>-values of triplets with <i>R</i> in [500, 1000, 5000, 10000] and stability of significance.

<p>The matrix in (<b>A</b>) shows the scatterplots (lower half) and QQ-plots (upper half) of 521 triplet average <i>p</i>-values down to 10⁻⁶ with sampling rates (<i>R</i>) ranging from 500 to 10000. The histograms in (<b>B</b>) demonstrate the effect of different values for <i>R</i> on the coefficient of variation (CV). The vertical red lines indicate the CV at the 90^th percentile. The Venn diagram in (<b>C</b>) illustrates the stability of p-values for KEGG terms in a triplicate with <i>R</i> = 1000. The number of terms having a <i>p</i>-value <0.05 ranges from 60 to 62 and 59 terms (∼95%) were present in all replicates.</p

Deletion of single <i>miR-1/133a</i> clusters does not cause gross morphological alterations in the heart but results in decreased ejection fraction in <i>miR-1-1/133a-2</i> mutants after TAC.

<p>(A–C) No morphological abnormalities are discernable on frontal sections through hearts of <i>miR-1-1/133a-2</i> and <i>miR-1-2/133a-2</i> homozygous mutants. (D, E) Transverse aortic constriction led to an increase in wall thickness (D) and left ventricular mass (E) in comparison to sham-operated mice wildtype or <i>miR-1/133a</i> single <i>knock-out</i> mice as measured by MRI. (F) <i>miR-1-1/133a-2</i> but not <i>miR-1-2/133a-2</i> homozygous mutants showed a reduction in ejection fraction compared to wild type mice. (G) TAC-induced pressure overload resulted in a comparable increase in ANP levels in single cluster mutants and wild type controls. (H, I) qRT-PCR analysis (Taqman) of miR-1 and miR-133a expression in different single cluster mutant strains after TAC. No significant increase of miR-1 expression in <i>miR-1-1/133a-2</i> and <i>miR-1-2/133a-1</i> mutants after TAC compared to sham-operated mice while expression levels of miR-133a dropped slightly after TAC in both single cluster mutants.</p