Fluorine-containing Alkyl Research Articles

Structure and biological property studies of the fluorinated sulfonic esters derived from 2-hydroxy-4-(hydroxy/methoxy)acetophenone as inhibitors of biochemical targets linked to type 2 diabetes mellitus

Small molecule multi-target drugs substituted with fluorine atom/s or fluorine-containing group/s continue to attract considerable interest in medicinal chemistry due to their advantages in the treatment of multifactorial diseases. In this study, fluorine-containing alkyl and benzenesulfonyl chloride building blocks were reacted with 2,4-dihydroxyacetophenone 1a or 2-hydroxy-4-methoxyacetophenone 1b to afford the corresponding sulfonic ester derivatives 2a–f and 2g–j, respectively. Detailed crystallographic characterization was performed on a representative compound from each series. The compounds were evaluated through enzymatic assays in vitro for potential to inhibit biochemical targets linked to type 2 diabetes mellitus. Compound 1a and its 4-(4-fluorophenyl)sulfonyl derivative 2d exhibited strong and significant inhibitory effect in vitro against α-glucosidase (IC50 = 0.97 ± 0.02 μM and 0.81 ± 0.07 μM, respectively) and α-amylase (IC50 = 6.89 ± 0.04 μM and 4.87 ± 0.02 μM, respectively) compared to acarbose (IC50 = 8.60 ± 0.20 μM and 1.96 ± 0.03 μM, respectively). The presence of a 4-fluorophenylsulfonyl moiety resulted in moderate inhibitory activity for 2d (IC50 = 27.05 ± 0.01 μM) against protein tyrosine phosphatase 1 beta (PTP1B) compared to the PTP1B inhibitor, suramin (IC50 = 4.63 ± 0.003 μM). The test compounds exhibited strong to moderate nitric oxide radical scavenging activity in vitro against ascorbic acid (IC50 = 5.53 ± 0.03 μM) with IC50 values in the range 0.05–19.30 μM. Compounds 1a and 2d did not inhibit superoxide dismutase (SOD) activity. Molecular docking revealed the involvement of hydrophobic, hydrophilic and electrostatic interactions with amino acid residues in the active site of the test enzymes.

Unique fluorophilic pores engineering within porous aromatic frameworks for trace perfluorooctanoic acid removal.

Perfluorooctanoic acid (PFOA), a representative of per/polyfluorinated alkyl substances, has become a persistent water pollutant of widespread concern due to its biological toxicity and refractory property. In this work, we design and synthesize two porous aromatic frameworks (PAF) of PAF-CF3 and PAF-C2F5 using fluorine-containing alkyl based monomers in tetrahedral geometry. Both PAFs exhibit nanosized pores (∼1.0nm) of high surface areas (over 800m2 g-1) and good fluorophilicity. Remarkable adsorption capacity (˃740mg g-1) and superior efficiency (˃24g mg-1 h-1) are achieved toward the removal of PFOA with 1μg L-1 concentration owing to unique C-F···F-C interactions. In particular, PAF-CF3 and PAF-C2F5 are able to reduce the PFOA concentration in water to 37.9ng L-1 and 43.3ng L-1, below EPA regulations (70ng L-1). The reusability and high efficiency give both PAFs a great potential for sewage treatment.

Novel fluorinated polycationic delivery of anti-VEGF siRNA for tumor therapy

Small-interfering RNA (siRNA) can specifically silence disease gene expression, bringing hope for the effective treatment of gene-related diseases. However, its use in vivo is limited due to the lack of efficient carriers. Therefore, it is necessary to construct carriers with high efficiency, low toxicity and serum stability. As a promising polycation carrier, polyethylenimine (PEI) can be further modified with a fluorine-containing alkyl chain that brings hydrophobic and oleophobic characteristics to its surface. In this study, low molecular weight PEI 1.8 kDa was selected and fluorinated through an anhydride reaction, and the product was named PEIF. In vitro experiments have shown that PEIF/siRNA polyplexes have suitable and stable particle size and potential, compress nucleic acids at a very low w/w ratio, and have the ability to effectively silence specific genes with low cytotoxicity. Compared with the polyplexes prepared using PEI 25 kDa, the PEIF/siRNA polyplexes were more stable in serum, showed a better antiangiogenic ability in in vivo experiments, and had a better tumor inhibition effect. The above results indicate that fluoropolymers based on the fluorine effect have great potential as gene delivery carriers for tumor therapy.

Covalent Attachment and Characterization of Perylene Monolayers on Si(111) and TiO2 for Electron-Selective Carrier Transport.

We functionalized chemically oxidized Si(111) and TiO2 surfaces with covalently attached rylene molecules and demonstrated further chemical conversion of the attached species. Base-catalyzed activation of perylene tetracarboxylic dianhydride (PTCDA) preceded reaction with phenylaminosilane-terminated surfaces, yielding surface-bound perylene via an imide linkage. Transflection infrared (IR) spectroscopy of the carbonyl vibrational region elucidated the presence of anhydride, imide, and ester species following each reaction stage. The presence of both anhydride and imide IR features following reaction with PTCDA validates successful perylene attachment. Subsequent functionalization of the surface-attached perylenes yielded IR spectra with little or no detectable anhydride features that indicate successful conversion to ester or imide species based on respective reactions with alkyl bromides or aryl amines. X-ray photoelectron spectroscopy quantified fractional coverages of surface-attached perylene species following a post-deposition derivatization with fluorine-containing alkyl bromides and with anilines. Overlayer model interpretation of the photoelectron results determined a perylene surface coverage of ∼15% relative to the surface density of Si(111) atop sites and a ∼10% surface coverage of imide-terminated perylene species. The interpreted coverage data yield an approximate conversion efficiency for the anhydride-to-imide derivatization at surface-attached perylenes of ∼66%. We discuss the present results in terms of possible coverage and packing on oxide-free silicon surfaces and the utilization of covalently attached rylene species as electron-transporting and hole-blocking connecting layers in molecular electronics and tandem-junction photovoltaic designs.

Fluorinated Poly(substituted methylene)s Prepared by Pd-Initiated Polymerization of Fluorine-Containing Alkyl and Phenyl Diazoacetates: Their Unique Solubility and Postpolymerization Modification

Pd-initiated polymerization of fluorine (F)-containing alkyl and phenyl diazoacetates is described. Polymerization of 2,2,2-trifluoroethyl diazoacetate [Et(CF3)DA] with π-allylPdCl afforded a C–C main chain polymer bearing a 2,2,2-trifluoroethoxycarbonyl group on each main chain carbon atom. The polymer showed upper critical solution temperature (UCST)-type phase separation in multiple common organic solvents with differing polarities. Although homopolymerization of 3,3,4,4,5,5,6,6,6-nonafluorohexyl diazoacetate [Hex(C4F9)DA] with a higher fluorine content yielded an insoluble product, copolymerization of Hex(C4F9)DA with non-fluorinated ethyl diazoacetate (EDA) proceeded homogeneously to give a soluble F-containing copolymer. Polymerization of a series of F-containing phenyl diazoacetates was also conducted with the same initiator, giving poly[(F-containing aryloxycarbonyl)methylene]s, which showed significant solubility differences depending on the substitution pattern of F atoms on the phenyl ring. Eff...

Facile one-pot preparation of allylic alcohols with a fluorine-containing alkyl group at the γ-position

A useful one-pot preparation method of allylic alcohols with fluorinated alkyl groups at the γ position was developed from the corresponding enoates by way of the DIBAL-mediated half reduction, followed by nucleophilic attack of Grignard reagents to aldehydes equilibrating with aluminium acetals.

ChemInform Abstract: Synthesis of Fluorine-Containing Alkyl 2-Cyano-3-oxocarboxylates. Reactions with Nucleophiles.

Fluorine-containing alkyl 2-cyano-3-oxocarboxylates were synthesized for the first time by the reaction of ethyl cyanoacetate with fluorine-substituted carboxylic acid halides or alkyl carboxylates. The reactions with hydrazine hydrate, phenylhydrazine, ando-phenylenediamine give hydrazinium (ammonium) enolates or products of acid decomposition.

Synthesis of fluorine-containing alkyl 2-cyano-3-oxocarboxylates. Reactions with nucleophiles

Fluorine-containing alkyl 2-cyano-3-oxocarboxylates were synthesized for the first time by the reaction of ethyl cyanoacetate with fluorine-substituted carboxylic acid halides or alkyl carboxylates. The reactions with hydrazine hydrate, phenylhydrazine, ando-phenylenediamine give hydrazinium (ammonium) enolates or products of acid decomposition.

Enantioselective deprotonation of 4-substituted cyclohexanones by chiral chelated lithium amides having a fluorine-containing alkyl group on amide nitrogen

Chiral chelated lithium armides ( 2e∼h) having a fluorine-containing alkyl group on amide nitrogen were found to induce high enantioselectivity in kinetic deprotonation of 4-substituted cyclohexanones ( 1a∼2d).

The mass spectra of the negative and positive ions of the methyl esters of the fluorine-substituted benzoic acids

1. A study has been made of dissociative electron capture by the molecules of the methyl esters of substituted benzoic acids with fluorine-containing alkyl substituents. Mass spectra of the positive ions of these compounds have been obtained. 2. The principal decomposition paths for the positive and negative molecular ions of these compounds have been established. Conjugation of the perfluoroalkyl and carbomethoxy groups through the benzene ring has a marked effect on dissociative electron capture. 3. The mass spectra of the negative ions are more sensitive to alteration of the molecular structure than are the mass spectra of the positive ions.