Recyclable Palladium Catalysts for the Heck/Sonogashira Reaction under Microwave‐assisted Thermomorphic Conditions

The reaction of allyl palladium(II) chloride dimer and 4,4′‐bis(R_fCH₂OCH₂)‐2,2′‐bpy, 1a–b , in the presence of AgOT_f resulted in the synthesis of cationic palladium complex, [Pd(η³‐allyl)(4,4′‐bis‐(R_fCH₂OCH₂)‐2,2′‐bpy)](OT_f), 2a–b where R_f = C₉F₁₉ ( a ), C₁₀F₂₁ ( b ), respectively. The reaction of [PdCl₂(CH₃CN)] or K₂PdCl₄ with 1b , gave rise to the synthesis of [PdCl₂(4,4′‐bis‐(C₁₀F₂₁CH₂OCH₂)‐2,2′‐bpy)], 3b . The quantitatively determined solubility curves of 2a–b and 3b in DMF indicated dramatic increase of solubility for 2a – b and 3b from ?40 to 90 °C. The catalyst‐recoverable Pd‐catalyzed Heck/Sonogashira reactions were successfully achieved in DMF with microwave‐assistance. The cationic Pd‐catalyzed Heck arylation of methyl acrylate was selected to demonstrate the feasibility of recycling 2a–b using DMF as a solvent under microwave‐assisted thermomorphic conditions. At the end of each cycle, the product mixtures were cooled, and then the catalysts were recovered by decantation. The Heck arylation catalyzed by 2b under microwave‐assisted mode exhibited good recycling results favoring the trans product. To our knowledge, this is the first example of cationic Pd‐catalyzed Heck arylation under microwave‐assisted thermomorphic conditions. Additionally, recoverable 3b ‐catalyzed Sonogashira reactions were also achieved successfully in DMF. The reactions under microwave‐assistance gave much better results in yield and in efficiency than that under conventional thermal heating.     

Fluorophilic properties of (perfluorooctyl)ethyldimethylsilyl substituted and tetramethyl(perfluoroalkyl) substituted cyclopentadienes and their Ti(IV), Rh(III), and Rh(I) complexes

Fluorous partition coefficients in perfluorohexane/toluene system for 37 fluorinated silylcyclopentadienes, titanium(IV) complexes derived from them, perfluoroalkyl substituted tetramethylcyclopentadienes, and their Rh(III) and Rh(I) complexes were determined. Specific fluorophilicity and fluorousness according to Kiss and Rábai were calculated for each compound with the help of molecular volume computed with the Gaussian program. The results show relative unimportance of fluorine content parameter for fluorophilicity as shown by a rhodium(I) complex being fluorophilic at fluorine content as low as 46.3%. As expected, fluorophilicity increased with the fluorous ponytail length and ponytail number in series of similar compounds, whereas polar M-Cl bonds were decreasing it. Fluorophilicities of tetramethyl(perfluoroalkyl)cyclopentadiene tautomers varied considerably despite only small differences in molecular volume being found. Most of the compounds were prepared previously, several new silylcyclopentadienes and titanium(IV) silylcyclopentadienyl complexes are reported here for completion.     

Synthesis and solid state structure of fluorous probe molecules for fluorous separation applications

A series of colored hydrocarbon and fluorocarbon tagged 1-fluoro-4-alkylamino-anthraquinones and 1,4-bis-alkylamino-anthraquinone probe molecules were synthesized from a (fluorinated) alkyl amine and 1,4-difluoroanthraquinone to aid in the development of fluorous separation applications. The anthraquinones displayed stacking of the anthraquinone tricycle and interdigitation of the (fluorinated) alkyl chains in the solid state. Furthermore, intramolecular N-H?O hydrogen bonds forced the hydrocarbon and fluorocarbon tags into a conformation pointing away from the anthraquinone tricycle, with the angle of the tricycle plane normal and the main (fluorinated) alkyl vector ranging from 1° to 39°. Separation of the probe molecules on fluorous silica gel showed that the degree of fluorination of the probe molecules plays only a minor role with most eluents (e.g., hexane/ethyl acetate and methyl nonafluorobutyl ethers/ethyl acetate). However, toluene as eluent caused a pronounced separation by degree of fluorination for fluorocarbon, but not hydrocarbon tagged probe molecules on both silica gel and fluorous silica gel. These studies suggest that hydrocarbon and fluorocarbon tagged anthraquinones are useful probe molecules for the development of laboratory scale fluorous separation applications.     

New alkylated and perfluoroalkylated phosphonic acids: Synthesis, adhesive and water-repellent properties on aluminum substrates

This paper describes the synthesis of phosphonic acids (R-S-(CH₂)₂-PO(OH)₂) containing a perfluoroalkylated chain (R = C₆F₁₃-(CH₂)₂, C₈F₁₇-(CH₂)₂) or an alkyl group (R = C₁₂H₂₅, C₁₈H₃₇). These compounds, obtained in excellent yield by telomerization of vinyl phosphonic acid in the presence of alkylated or perfluorinated mercaptans used as transfer agents, were characterized by ¹H, ¹⁹F and ³¹P nuclear magnetic resonance. Thermal characterization by differential scanning calorimetry (DSC) showed the presence of mesophases for compounds containing C₈F₁₇ and C₁₈H₃₇ end groups. A lamellar structure with a layered or bilayered organization was identified by small angle X-ray scattering (SAXS). Adhesion of these compounds on aluminum surfaces is improved by the presence of phosphonic groups. Hydrophobic properties of coated aluminum surfaces are enhanced by fluorinated groups.     

Branched polyfluorinated triflate—An easily available polyfluoroalkylating agent

A novel branched polyfluoroalkyl triflate was prepared from readily available (perfluorohexyl)propyl iodide in five steps with high overall yield. The reactivity of the triflate has been tested in model reactions with methyl gallate (O-nucleophile) and benzylamine (N-nucleophile). The reactions yielded good amounts of the desired polyfluorinated products.     

Spectrally Combined Encoding for Profiling Heterogeneous Circulating Tumor Cells Using a Multifunctional Nanosphere-Mediated Microfluidic Platform

Comprehensive phenotypic profiling of heterogeneous circulating tumor cells (CTCs) at single-cell resolution has great importance for cancer management. Herein, a novel spectrally combined encoding (SCE) strategy was proposed for multiplex biomarker profiling of single CTCs using a multifunctional nanosphere-mediated microfluidic platform. Different cellular biomarkers uniquely labeled by multifunctional nanosphere barcodes, possessing identical magnetic tags and distinct optical signatures, enabled isolation of heterogeneous CTCs with over 91.6 % efficiency and in situ SCE of phenotypes. By further trapping individual CTCs in ordered microstructures on chip, composite single-cell spectral signatures were conveniently and efficiently obtained, allowing reliable spectral-readout for multiplex biomarker profiling. This SCE strategy exhibited great potential in multiplex profiling of heterogeneous CTC phenotypes, offering new avenues for cancer study and precise medicine.     

Fluorocarbon-bonded magnetic mesoporous microspheres for the analysis of perfluorinated compounds in human serum by high-performance liquid chromatography coupled to tandem mass spectrometry

We report herein an extraction method for the analysis of perfluorinated compounds in human serum based on magnetic core–mesoporous shell microspheres with decyl-perfluorinated interior pore-walls (Fe₃O₄@mSiO₂-F₁₇). Thanks to the unique properties of the Fe₃O₄@mSiO₂-F₁₇ microspheres, macromolecules like proteins could be easily excluded from the mesoporous channels due to size exclusion effect, and perfluorinated compounds (PFCs) in protein-rich biosamples such as serum could thus be directly extracted with the fluorocarbon modified on the channel wall without any other pretreatment procedure. The PFCs adsorbed Fe₃O₄@mSiO₂-F₁₇ microspheres could then be simply and rapidly isolated by using a magnet, followed by being identified and quantified by LC–MS/MS (high-performance liquid chromatography coupled to tandem mass spectrometry). Five perfluorinatedcarboxylic acids (C6, C8–C11) and perfluorooctane sulfonate (PFOS) were selected as model analytes. In order to achieve the best extraction efficiency, some important factors including the amount of Fe₃O₄@mSiO₂-F₁₇ microspheres added, adsorption time, type of elution solvent, eluting solvent volume and elution time were investigated. The ranges of the LOD were 0.02–0.05 ng mL⁻¹ for the six PFCs. The recovery of the optimized method varies from 83.13% to 92.42% for human serum samples.     

Synthesis of perfluorinated analogs of DOTA and NOTA: bifunctional chelating groups with potential applications in hybrid molecular imaging

The synthesis of novel NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) and DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelating groups bearing perfluorinated appendages is described. DOTA and NOTA groups are used in the production of radiopharmaceutical agents for PET and SPECT imaging (by chelation of radioactive metal ions), as well as MRI contrast agents (by chelation of lanthanide Ln³⁺ ions). The novel perfluorinated variants disclosed herein will enhance the synthesis and purification of such agents, as they are compatible with fluorous purification strategies. Moreover, the perfluorous tag is anticipated to be detectable by ¹⁹F-MRI, suggesting future applications in hybrid molecular imaging such as PET–MRI.     

Addition of urea and thiourea to electrophoresis sample buffer improves efficiency of protein extraction from TCA/acetone‐treated smooth muscle tissues for phos‐tag SDS‐PAGE

Phosphorylation analysis by using phos‐tag technique has been reported to be suitable for highly sensitive quantification of smooth muscle myosin regulatory light chain (LC₂₀) phosphorylation. However, there is another factor that will affect the sensitivity of phosphorylation analysis, that is, protein extraction. Here, we optimized the conditions for total protein extraction out of trichloroacetic acid (TCA)‐fixed tissues. Standard SDS sample buffer extracted less LC₂₀, actin and myosin phosphatase targeting subunit 1 (MYPT1) from TCA/acetone treated ciliary muscle strips. On the other hand, sample buffer containing urea and thiourea in addition to lithium dodecyl sulfate (LDS) or SDS extracted those proteins more efficiently, and thus increased the detection sensitivity up to 4–5 fold. Phos‐tag SDS‐PAGE separated dephosphorylated and phosphorylated LC₂₀s extracted in LDS/urea/thiourea sample buffer to the same extent as those in standard SDS buffer. We have concluded that LDS (or SDS) /urea/thiourea sample buffer is suitable for highly sensitive phosphorylation analysis in smooth muscle, especially when it is treated with TCA/acetone.     

A novel fluorous palladium catalyst for Suzuki reaction in fluorous media

Palladium(II) perfluorooctanesulfonate [Pd(OSO₂R_f8)₂] catalyses the highly efficient Suzuki reaction in the presence of a catalytic amount of perfluoroalkylated-pyridine as a ligand in a fluorous biphase system (FBS). The fluorous phase containing the active palladium species is easily separated and can be reused several times without a significant loss of catalytic activity.