The contribution of fluoropolymer thermolysis to trifluoroacetic acid (TFA) in environmental media.

The source of trifluoroacetic acid (TFA) has long been a controversial issue. Fluoropolymer thermolysis is expected to be a potential anthropogenic source except for CFC alternatives. However, its TFA yield and contributions have rarely been reported more recently. In this study, we investigated the thermal properties of three kinds of fluoropolymers, including poly (vinylidene fluoride-co-hexafluropropylene) (PVDF-HFP), poly (vinylidene fluoride-co-chlorotrifluoroethylene) (PVDF-CTFE) and poly (tetrafluoroethylene) (PTFE). A laboratory simulation experiment was then performed to analyze the TFA levels in the thermolysis products and hence to examine the TFA yields of these fluoropolymers. Thermolysis of these fluoropolymers occurred in the temperature ranges from ∼400 °C to ∼650 °C, with the peak weight loss rate at around 550-600 °C. TFA could be produced through fluoropolymer thermolysis when being heated to 500 °C and above. Average TFA yields of PTFE, PVDF-HFP and PVDF-CTFE were 1.2%, 0.9% and 0.3%, respectively. Furthermore, the contribution of fluoropolymer thermolysis and CFC alternatives to rainwater TFA in Beijing, China was evaluated by using a Two-Box model. The degradation of fluoropolymers and HCFCs/HFCs could explain 37.9-43.4 ng L-1 rainwater TFA in Beijing in 2014. The thermolysis of fluoropolymers contributed 0.6-6.1 ng L-1 of rainwater TFA, accounting for 1.6-14.0% of the TFA burden from all the precursors which were considered here.

Synthesis and Evaluation of the Antioxidant Activity of Lipophilic Phenethyl Trifluoroacetate Esters by In Vitro ABTS, DPPH and in Cell-Culture DCF Assays.

Polyphenols are natural compounds showing a variety of health-promoting effects. Unfortunately, due to low lipid solubility, their applications in the pharmaceutical, food, and cosmetic industries are limited. With the aim of obtaining novel lipophilic derivatives, the present study reports the synthesis of a series of phenethyl trifluoroacetate esters containing up to two hydroxyl groups in the aromatic ring. Experimental logP values confirmed a greater lipophilicity of the novel compounds compared to the parent compounds. The radical scavenging capacity of all phenethyl trifluoroacetate esters was evaluated by in vitro assays (ABTS, DPPH) and in cultured cells (L6 myoblasts and THP-1 leukemic monocytes) using 2',7'-dichlorodihydrofluorescein diacetate. These data revealed that the esters showed a good antioxidant effect that was strictly dependent on the grade of hydroxylation of the phenyl ring. The lack of toxicity, evaluated by the MTT assay and proliferation curves, makes these trifluoroacetates attractive derivatives for pharmaceutical, food, and cosmetic applications.

Chemical synthesis of membrane proteins by the removable backbone modification method.

Chemical synthesis can produce membrane proteins bearing specifically designed modifications (e.g., phosphorylation, isotope labeling) that are difficult to obtain through recombinant protein expression approaches. The resulting homogeneously modified synthetic membrane proteins are valuable tools for many advanced biochemical and biophysical studies. This protocol describes the chemical synthesis of membrane proteins by condensation of transmembrane peptide segments through native chemical ligation. To avoid common problems encountered due to the poor solubility of transmembrane peptides in almost any solvent, we describe an effective procedure for the chemical synthesis of membrane proteins through the removable-backbone modification (RBM) strategy. Two key steps of this protocol are: (i) installation of solubilizing Arg4-tagged RBM groups into the transmembrane peptides at any primary amino acid through Fmoc (9-fluorenylmethyloxycarbonyl) solid-phase peptide synthesis and (ii) native ligation of the full-length sequence, followed by removal of the RBM tags by TFA (trifluoroacetic acid) cocktails to afford the native protein. The installation of RBM groups is achieved by using 4-methoxy-5-nitrosalicyladehyde by reduction amination to incorporate an activated O-to-N acyl transfer auxiliary. The Arg4-tag-modified membrane-spanning peptide segments behave like water-soluble peptides to facilitate their purification, ligation and mass characterization.

Optimized Solid-Phase-Assisted Synthesis of Oleic Acid Containing siRNA Nanocarriers.

Cationic lipo-oligomers containing unsaturated oleic acid are potent siRNA carriers based on electrostatic and hydrophobic lipo-polyplex formation and endosomal membrane destabilization. Lipo-oligomers can be produced by solid-phase-supported synthesis in sequence-defined form. However, the trifluoroacetic acid (TFA)-mediated removal of acid-labile protecting groups and cleavage from the resin can be accompanied by side products caused by the addition of TFA to the double bonds of oleic acid. Under aqueous conditions, these TFA adducts of oleic acid are converted into hydroxystearic acid derivatives. The cleavage protocol was optimized to decrease TFA adducts. The pure oleic acid (C18:1) containing lipo-oligomer was compared with analogous structures containing saturated or modified hydrophobic moieties (stearic acid (C18:0), hydroxystearic acid, and 8-nonanamidooctanoic acid). The structure containing intact oleic acid shows favorable pH dependency of lytic activity, efficient gene silencing, and excellent cell tolerability relative to its counterparts.

Metal and base free synthesis of primary amines via ipso amination of organoboronic acids mediated by [bis(trifluoroacetoxy)iodo]benzene (PIFA).

A metal and base free synthesis of primary amines has been developed at ambient temperature through ipso amination of diversely functionalized organoboronic acids, employing a combination of [bis(trifluoroacetoxy)iodo]benzene (PIFA)-N-bromosuccinimide (NBS) and methoxyamine hydrochloride as the aminating reagent. The amines were primarily obtained as their trifluoroacetate salts which on subsequent aqueous alkaline work up provided the corresponding free amines. The combination of PIFA-NBS is found to be the mildest choice compared to the commonly used strong bases (e.g. n-BuLi, Cs2CO3) for activating the aminating agent. The reaction is expected to proceed via activation of the aminating reagent followed by B-N 1,2-aryl migration.

Alternative synthesis of 3-acetyl, 3-epoxy, and 3-formyl chlorins from a 3-vinyl chlorin, methyl pyropheophorbide-a, via iodination.

We developed novel methods to convert the C3-vinyl group of a chlorophyll derivative, methyl pyropheophorbide-a, into an acetyl group, an epoxy group, and a formyl group via iodination with I2 and phenyliodine(III) bis(trifluoroacetate). Reaction of the iodinated intermediate with ethylene glycol and subsequent treatment with base led to formation of the C3-acetyl chlorin. Reaction of the iodinated intermediate with ethylenediamine afforded the C3-oxiranyl chlorin. The C3-formyl chlorin was readily derived from the epoxide without hazardous reagents such as OsO4. These reactions were facile and useful alternatives to the previous methods.

Microwave-assisted synthesis of HYNIC protected analogue for 99mTc labeled antibody.

We described herein a simple and efficient microwave assisted synthesis of HYNIC analogues. Two different activated esters of HYNIC, the hydrazine protected with a trifluoroacetyl group (5) and the free hydrazine (6) were conjugated to the monoclonal antibody Nimotuzumab. Technetium-99m radiolabeling of Nimotuzumab was achieved with high efficiency using 5 and 6 derivates. The NHS-HYNIC-Tfa derivate allowed better labeling yields during longer times of preservation of the conjugated antibody.

Rapid and efficient trifluoromethylation of aromatic and heteroaromatic compounds using potassium trifluoroacetate enabled by a flow system.

Going to the source: The trifluoromethylation of aryl/heteroaryl iodides has been demonstrated using a flow system, thus enabling a rapid rate of reaction. A broad spectrum of trifluoromethylated compounds was prepared in good to excellent yields using CF3 CO2 K as the trifluoromethyl source. The process has the advantage of short reaction times and uses convenient [CF3 ] sources.

Preparation and stabilization of aluminium trifluoroacetate fluoride sols for optical coatings.

For the first time, aluminium fluorides in liquid phase are available for optical applications. By modifying the conditions of the fluorolytic sol-gel synthesis of aluminium fluorides transparent sols with low viscosities were obtained. These sols consist mainly of small oligomeric or cluster units of aluminium fluoride which are not measurable by DLS, WAXS, SAXS and show unusual narrow signals in solid state NMR. Isolated particles with diameters up to five nanometers can be identified by TEM measurements and allow the use of their sols in optical and anti reflecting coatings. The sol particles were modified by trifluoroacetic acid to prevent agglomeration, and as a result, the obtained xerogels can be re-dispersed transparently in organic solvents.

Synthesis of α-halo-α,α-difluoromethyl ketones by a trifluoroacetate release/halogenation protocol.

Three series of α-halo-α,α-difluoromethyl ketones are prepared from highly α-fluorinated gem-diols by exploiting the facile release of trifluoroacetate, followed by immediate trapping of the liberated α,α-difluoroenolate with an electrophilic chlorine, bromine, or iodine source. The products are typically isolated in good yields, even in the case of sensitive, α-iodo-α,α-difluoromethyl ketones. Also, we demonstrate that an α-iodo-α,α-difluoromethyl ketone will participate in a copper-promoted reaction to forge a new carbon-carbon bond.

Improved synthesis of (E)-12-nitrooctadec-12-enoic acid, a potent PPARγ activator. Development of a "buffer-free" enzymatic method for hydrolysis of methyl esters.

Endogenous nitro-fatty acids, acting as partial agonist of PPARγ, are able to lower the insulin and glucose levels without the side effects associated with common antidiabetic drugs. (E)-12-Nitrooctadec-12-enoic acid, a potent activator of this peroxisome receptor, was synthesized in a very efficient sequence via a Henry-retro-Claisen ring fragmentation, followed by a novel enzymatic cleavage of methyl esters. The latter method was then applied in the last step of the synthesis of a few labile natural products, such as prostaglandins, isoprostanes, and phytoprostanes.

Trifluoroselenoacetic acid, CF(3)C(O)SeH: preparation and properties.

The hitherto unknown trifluoroselenoacetic acid was prepared through the reaction of trifluoroacetic acid with Woollins' reagent. The compound was fully characterized by mass spectrometry, (1)H, (19)F, (77)Se, and (13)C NMR, UV-visible, IR and Raman spectroscopy, and the boiling point at 46 °C was estimated from the vapor pressure curve. An IR matrix isolation study revealed the presence of two different syn-anti and anti-syn conformers. The IR spectra of the two stereoisomers have been assigned, aided by DFT, and ab initio calculations. The UV photolysis of Ar matrix isolated CF(3)C(O)SeH yielded CO, OCSe, CF(3)SeH, and CHF(3). Apart from CF(3)SeH, these products were also obtained by vacuum flash-pyrolysis (310 °C) of gaseous CF(3)C(O)SeH. Instead of CF(3)SeH, CF(2)Se, and HF were detected among the pyrolysis products. The different decomposition pathways of CF(3)C(O)SeH are discussed.

A new H2O2/acid anhydride system for the iodoarene-catalyzed C-C bond-forming reactions of phenols.

We have succeeded in the first versatile iodoarene-catalyzed C-C bond-forming reactions by development of a new reoxidation system at low temperatures using stoichiometric bis(trifluoroacetyl) peroxide A in 2,2,2-trifluoroethanol (TFE). The catalytic system supplies a wide range of substrates and functional availabilities sufficient to be used in the key synthetic process of producing biologically important Amaryllidaceae alkaloids.

Determination of synthetic polypeptide conformations and molecular geometrical parameters by nonaqueous CE.

The aim of this work was to study changes in homopolypeptide chain conformation as a function of the number of residues by the modeling of the electrophoretic mobility. For this purpose, the frictional coefficients of poly(N(epsilon)-trifluoroacetyl-L-lysine) with different number of residues (up to 11) were determined from the absolute ionic mobilities and modeled by the hydrodynamic frictional coefficient of an equivalent cylinder. This approach allowed determination of geometrical parameters of the polypeptide chain in a liquid phase (nonaqueous solution of the BGE). The fact that the BGE and analyte are dissolved in mixed (methanol-ACN) organic solvent implied to take into account different effects and corrections that are generally not considered in aqueous solvent: namely, the effect of ion-pairs between constituents of the BGE for the calculation of the ionic strength, the effect of ion-pairs between the solutes and the electrolyte counterions and the correction due to the dielectric friction (Hubbard-Onsager equations). In addition, the influence of the ionic strength on the electrophoretic mobility was corrected using the Pitts equation, and the effect of lateral charges due to a slight deprotonation of the -NH- group in the lateral chain was also considered. From this modeling, molecular geometrical parameters relative to the linear and helicoïdal conformations were obtained with very good correlation coefficients. Interestingly, this work also points out that the use of ionic mobility modeling for extracting molecular geometrical parameters can also be applied to end-charged polypeptides with slightly charged lateral chains (3% of elementary charge per residue).

Trifluoroacetyl-HYNIC peptides: synthesis and 99mTc radiolabeling.

Fmoc-lys(HYNIC-Boc)-OH, a precursor for solid-phase synthesis of 99mTc-labeled peptides, was synthesized efficiently without HPLC purification. HPLC-ESMS showed that deprotection and decoupling of peptide from the resin with trifluoroacetic acid gave initially HYNIC-peptide, which was trifluoroacetylated upon prolonged incubation. The trifluoroacetyl-HYNIC group was hydrolyzed during 99mTc labeling, rendering deprotection unnecessary. Trifluoroacetyl-HYNIC peptide was 99mTc-labeled as efficiently, producing the same product, as HYNIC-peptide. These modifications enhance the versatility of HYNIC for 99mTc peptide labeling.

S-(fluoroformyl)O-(trifluoroacetyl) thioperoxide, FC(O)S-OC(O)CF3: gas-phase structure and conformational properties.

The geometric structure and conformational properties of S-(fluoroformyl)O-(trifluoroacetyl) thioperoxide, FC(O)S-OC(O)CF3, were investigated by gas electron diffraction, matrix isolation infrared spectroscopy, and quantum chemical calculations (B3LYP with the 6-31G and aug-cc-pVTZ basis sets and MP2 with the 6-31G basis set). The experimental methods result in a mixture of two conformers with gauche conformation around the S-O bond. In the main conformer (82(7)% according to GED at 298 K), the C=O bond of the FC(O) group is oriented syn with respect to the S-O bond and phi(C-S-O-C) = 75(3) degrees . In the minor conformer (18(7)%), this C=O is oriented anti. Both conformers possess syn orientation of the C=O bond of the CF3C(O) group. The conformational properties and geometric parameters are reproduced reasonably well by the quantum chemical calculations, except for the S-O bond length, which is predicted too long by 0.04 A (B3LYP/aug-cc-pVTZ).

DSA: a new internal standard for NMR studies in aqueous solution.

[structure: see text] The widely used internal standard for NMR studies in aqueous solution DSS (sodium 4,4-dimethyl-4-silapentane-1-sulfonate) can interact with cationic peptides, diminishing its value for such studies. This paper introduces DSA (4,4-dimethyl-4-silapentane-1-ammonium trifluoroacetate) as a new internal standard that does not suffer from this problem.

Pentafluoropropionyl and trifluoroacetyl groups for temporary hydroxyl group protection in oligomannoside synthesis.

Pentafluoropropionyl (PFP) and trifluoroacetyl (TFA) esters were demonstrated to be useful in facile oligosaccharide synthesis. These were well compatible with glycosylation conditions and removable by treatment with pyridine-EtOH, with complete preservation of acetyl groups. Analytically pure products were obtained quantitatively, simply by evaporating the reaction mixtures. Using O-PFP and O-TFA carrying glycosyl halides, trisaccharide (Manalpha1-->2Manalpha1-->2Man) and tetrasaccharide (Glcalpha1-->3Manalpha1-->2Manalpha1-->2Man) portions of monoglucosylated high-mannose type dodecasaccharide (Glc(1)Man(9)GlcNAc(2)), a putative ligand for the ER chaperon, calnexin and calreticulin, were synthesized.

Protease-catalyzed peptide synthesis for the site-specific incorporation of alpha-fluoroalkyl amino acids into peptides.

Substitution of native amino acids by fluoroalkyl analogues represents a new approach for the design of biologically active peptides with increased metabolic stability as well as defined secondary structure and provides a powerful label for spectroscopic investigations. Here, we introduce a methodology for the incorporation of sterically demanding C(alpha)-fluoroalkyl amino acids into the P(1) position of peptides catalyzed by the commercially available proteases trypsin and alpha-chymotrypsin. The combination of 4-guanidinophenyl ester of C(alpha)-fluoroalkyl amino acids as substrate mimetics with frozen-state reaction conditions provided the most efficient strategy for protease-catalyzed site-specific introduction of this kind of nonnatural amino acids into peptide sequences. Consequently, a library of di-, tri-, and tetrapeptides containing alpha-methyl, alpha-difluoromethyl, and alpha-trifluoromethyl alanine, leucine, and phenylalanine in the P(1) position was synthesized catalyzed by trypsin as well as alpha-chymotrypsin. Trypsin was shown to be the more versatile protease.