Hexafluoroisopropanol Research Articles

Re2O7/HReO4 Mediated Intramolecular Hydroacyloxylation of Unactivated Alkenes: A Dual Hydrogen-Bonding Effect

This publication describes the application of Re2O7 in hexafluoroisopropanol (HFIP) for the activation of inert as well as electronically deactivated olefins to facilitate a challenging intramolecular hydroacyloxylation reaction. Both HFIP and an internal carboxy group have been proven to be crucial for the successful implementation of this transformation; these are proposed to assist the formation and stabilization of the key cationic intermediate via hydrogen-bonding interactions with perrhenate anion (ReO4-).

Electrochemical C(sp3)-H Lactonization of 2-Alkylbenzoic Acids toward Phthalides.

Herein, we report direct electrochemical C(sp3)-H lactonization of 2-alkylbenzoic acids toward phthalides. The reaction provides a wide substrate scope of 2-alkylbenzoic acids bearing primary to tertiary C(sp3)-H bonds by utilizing a graphite anode, dichloromethane (DCM) solvent, hexafluoroisopropanol (HFIP) cosolvent, and n-Bu4NClO4 electrolyte. Our synthetic approach offers a simple, intuitive, and atom-economical protocol to synthesize various phthalides (25 examples, up to 92% yield) and obtain other 5- and 6-membered lactones (10 examples, up to 83% yield).

Polypeptide‐PEG Conjugates via Ring Opening Polymerization of l‐Alanine N‐Carboxyanhydride

AbstractThe synthesis of well‐defined homo‐ and co‐polypeptides of L‐alanine (L‐Ala) by ring‐opening polymerization (ROP) of its N‐carboxyanhydride (NCAs), either via suspension/interfacial‐ or solution phase‐polymerization using 10‐undecene‐1‐amine and α,ω‐diamino poly(ethylene glycol) (8 or 1.5 kDa) as primary amine initiators is reported. When conducting ROP of NCA‐alanine under suspension/interfacial conditions, back‐biting can be preferably eliminated to reach enhanced control of the polymerization. Well‐defined structures of the resulting homo‐polypeptides with chain lengths ranging from n = 9 to 31 and the resulting amphiphilic polyalanine conjugates with molecular weights ranging from 3.8 to 15.3 kDa and a degree of polymerization of n = 18 to 102 are obtained. Structural characterization is performed via 1H‐NMR, gel permeation chromatography (GPC) in hexafluoroisopropanol (HFIP), and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF‐MS). Subsequently, the folding of the homo‐ and triblock amphiphilic co‐polypeptides under a variety of parameters such as temperature, chain length, and backbone composition and the further transitions of these secondary structures are investigated in HFIP and HFIP‐H2O mixtures via circular dichroism (CD) spectroscopy. A solvent induced helical switch from a 310‐helix to a α‐helix when changing from HFIP to HFIP–water mixtures is observed, with water inducing helicity stronger in both, homo‐polyalanine and poly(alanine)‐PEG‐poly(alanine) triblock copolymers.

Hexafluoroisopropanol decreases liver ischemia-reperfusion injury by downregulation of high mobility group box-1 protein.

Liver ischemia-reperfusion (IR) injury is associated with poor outcome after liver transplantation and liver resections. Hexafluoroisopropanol (HFIP) is a tri-fluorinated metabolites of volatile anesthetics and has modulatory effects on inflammation that have been observed mainly in cell culture experiments. In this survey, we investigated the effects of HFIP in a rat model of normothermic hepatic ischemia-reperfusion injury. Twenty-four male Wistar rats were randomized into three groups: (1) control in which animals were submitted to 30 min of partial liver ischemia with resection of non-ischemic liver lobes immediate after reperfusion, (2) pre-ischemia (PI) group in which animals received intravenous HFIP (67 mg/kg) 5min before liver ischemia, and (3) pre-reperfusion (PR) group in which animals received intravenous HFIP (67 mg/kg) 5min before reperfusion. Four hours after reperfusion, all animals were euthanized for sample collection. Aspartate and alanine transaminases, glucose, and high mobility group box-1 (HMGB-1) protein concentrations showed a significant decreased, and malondialdehyde was increased in the PR group compared with control and PI groups. Interleukin 6 (IL-6) was increased in the PI group compared with control and PR groups. IL-10 and -12 were increased in the PR and PI groups, respectively, when compared with the control group. Glucose decreased in the PR when compared with the control group. Post-conditioning with HFIP led to a decrease in hepatocellular injury and was associated with a downregulation of HMGB-1. The HFIP resulted in a better control of inflammatory response to ischemia-reperfusion even without causing a reduction in oxidative stress.

Structure of AQEE-30 of VGF Neuropeptide in Membrane-Mimicking Environments.

AQEE-30 is one of the VGF peptides, which are derived from the VGF polypeptide precursor, and related to various physiological phenomena including neuroprotective effects in Huntington's disease and amyotrophic lateral sclerosis (ALS). Although various functions of AQEE-30 have been reported so far, the structure of this peptide has not been reported yet. In this study, the structure of human AQEE-30 was investigated in hexafluoroisopropanol (HFIP) and dodecyl phosphocholine (DPC) micelle solutions, using circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. CD results showed that AQEE-30 had a partial helical structure in aqueous buffer, and the helical structure was stabilized in the HFIP and DPC micelle solutions. The 3D structures determined by NMR spectroscopy showed that AQEE-30 adopted mainly α-helical structure in both the HFIP and DPC micelle solutions. The surface of AQEE-30 showed that it was predominantly negatively charged. The residues from 601 to 611 in both the HFIP and DPC micelle solutions showed amphiphilicity with four negatively charged residues, glutamate. The C-terminal consecutive arginine residues formed a partial positively charged surface. These results suggest an α-helical active structure of AQEE-30 in the cell-membrane environment.

Nonaqueous Capillary Zone Electrophoresis for Polyesters and Polyamides Using Hexafluoroisopropyl Alcohol as Electrophoretic Medium

Nonaqueous capillary zone electrophoresis (NACZE) utilizing cationic reagents as an electrophoresis promoter has the potential for separating water-insoluble synthetic polymers and that with tetrahydrofuran based electrophoretic media containing cationic reagents has been reported. In this study, NACZE using hexafluoroisopropyl alcohol (HFIP)-based media was developed for separating polyesters and polyamides, which were insoluble in tetrahydrofuran. Nonaqueous media of HFIP containing 400 mM cetyltrimethylammonium chloride (CTAC) and 50 mM trihexyl(tetradecyl)phosphonium chloride (P66614Cl) were used, and it was found that hydrophobic P66614 cation enhanced the electrophoresis of both polyesters and polyamides compared with cetyltrimethylammonium cation. The media containing CTAC resulted in partially separated poly(ethylene terephthalate)/poly(hexamethylene terephthalate) and poly(ethylene terephthalate)/poly(ethylene naphthalate), but P66614Cl failed to separate them. By contrast, nylon 6I and nylon 6/6I were separated with the P66614Cl media, whereas they were co-eluted in the media with CTAC.

New insights into the excited state of an A-D-A quadrupolar molecule strongly hydrogen bonded to molecules of methanol and hexafluoro isopropanol

In this work, we carried out density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations to study the hydrogen-bonding dynamics of 2,5-bis(4- cyanophenyl)-1,4-bis(4-methylphenyl)-1,4-dihydropyrrolo [3,2-b] pyrrole (ADA) in strongly H-bonding liquids. ADA, is a quadrupolar A–π–D–π–A type molecule (A-D-A), where A and D are electron-accepting and electron-donating moieties. Our theoretical results are consistent with previously reported experimental data. According to our computations, the CN···HO intermolecular hydrogen bonds formed between ADA and methanol, and between ADA and hexafluoro isopropanol are tremendously strengthened in the electronically excited-state upon the photoexcitation of their hydrogen-bonded complexes. The enhancement of the intermolecular hydrogen bond motives the dispersion of holes and electrons and the asymmetry of the ADA molecules in strongly H-bonded liquids, which promotes the red shift of the CN stretching vibration and the changes in the form of the solvent ADA around. The degree of asymmetry harm is associated to the solvent proton-donating ability and the phenomenon of increased asymmetry can be prolonged to the application of different dye molecules. The lookup will help experimenters develop different dyes with excellent performance.

Oxidative bridgehead functionalization of (4 + 3) cycloadducts obtained from oxidopyridinium ions.

Treatment of selected (4 + 3) cycloadducts derived from oxidopyridinium ions with N-iodosuccinimide (NIS) in hexafluoroisopropanol (HFIP) resulted in the formation of bridgehead ethers via a net oxidative C-H activation.

P030 Highly slow-release antifungal wound dressing for chronic dermatophytosis

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM ObjectivesThe aim of this research was to make a biocompatible and affordable nanofibrous wound dressing that is able to release terbinafine at the site of chronic superficial fungal infection over time.MethodsPolymer solution (10%) of poly (caprolactone) (PCL) was prepared in hexafluoroisopropanol (HFIP). Terbinafine hydrochloride (TFH) was added equal to 5% of PCL weight for drug-loaded samples. Electrospinning was performed with a 27-G-needle equipped syringe at a distance of 15 cm which the injection flow rate of the solution was 0.2 ml/h and a 30 kV voltage was applied. The measurements of drug release were performed with HPLC. Antifungal tests were done on three different fungal species and MTT assay was done based on ISO-10993 on 24 h L929 cells. The drug release was monitored for 144 h in a human body simulated system (incubation at 37°C, shaking by 30 rpm, and passing the drug through a wet Whatman filter into PBS).∷ΞResultsThe mean diameter of fibers was obtained at 1262 nm for PCL nanofibers without TFH and 249 nm for PCL nanofibers with TFH. The drug loading for PCL was 83.4%. Antifungal activity of PCL fibers was examined against a dermatophyte (Trichophyton mentagrophytes), a saprophyte (Aspergillus fumigatus), and a yeast (Candida albicans). The terbinafine hydrochloride-contained electrospun PCL fibers inhibited the growth of T. Mentagrophytes and A. Fumigatus but did not inhibit C. albicans growth. None of the samples showed cytotoxic effects after 24 h and 2 weeks.ConclusionsThe diameter of PCL nanofibers with TFH apparently decreased by fives times (P >.05). PCL nanofibers successfully inhibited two important fungal species while no toxicity was observed in MTT assay for its extraction of 2 weeks. They were able to release TFH slowly over time which makes them suitable for the treatment of chronic superficial fungal infections.

Environmentally Friendly Poly(Vinyl Alcohol)/Poly(Methyl Methacrylate) Materials with High-Performance by a Facile Fabrication Strategy

We have developed novel and environmentally friendly composite materials, consisting of polyvinyl alcohol (PVA) and polymethyl methacrylate (PMMA), for the first time, by dissolving PVA and PMMA in hexafluoroisopropanol (HFIP), followed by subsequent layout of PVA/PMMA/HFIP liquid films and removal of the HFIP. PMMA in the PVA/PMMA materials can remarkedly improve the mechanical properties (tensile strength and elongation at break) and the thermostabilities of the materials. Due to the hybridization of PVA with PMMA, the tensile strength and elongation at break can be improved as much as about 50% and 112%, respectively, compared with neat PVA material, whereas neat PMMA is brittle. Moreover, the materials are biodegradable and biocompatible. At the same time we have conducted systematic investigations to explore the influences of the PVA/PMMA mass ratio on the morphology, crystallinity, chemical structure, thermostability, mechanical properties, biodegradability, biocompatibility and the interactions between PVA and PMMA. The high-performance properties possessed by these materials will further broaden their practical application.

Transition Metal‐Free Cycloisomerization of Propargylic Amides to Oxazoles in Hexafluoroisopropanol (HFIP)

AbstractA transition metal‐free method for the cycloisomerization of propargylic amides to oxazoles was developed. The reaction utilizes in situ generated hydrogen chloride in hexafluoroisopropanol (HFIP). With the aid of Design of Experiments optimization a wide range of substrates was transformed into the desired oxazoles. The method allows product formation without side reactions eliminating the need for extensive work‐up and purification.magnified image

Optically Clear Silk Fibroin Films with Tunable Properties for Potential Corneal Tissue Engineering Applications: A Process-Property-Function Relationship Study.

Owing to the shortage of donor corneas and issues associated with conventional corneal transplantation, corneal tissue engineering has emerged as a promising therapeutic alternative. Biocompatibility and other attractive features make silk fibroin a biomaterial of choice for corneal tissue engineering applications. The current study presents three modes of silk fibroin film fabrication by solvent casting with popular solvents, viz. aqueous (aq), formic acid (FA), and hexafluoroisopropanol (HFIP), followed by three standard modes of postfabrication annealing with water vapor, methanol vapor, and steam, and systematic characterization studies including corneal cell culture in vitro. The results indicated that silk fibroin films made from aq, FA, and HFIP solvents had surface roughness (Rq) of 1.39, 0.32, and 0.13, contact angles of 73°, 85°, and 89°, water uptake% of 58, 29, and 27%, swelling ratios of 1.58, 1.3, and 1.28, and water vapor transmission% of 39, 26, and 22%, respectively. The degradation rate was in the order of aq > HF > FA, whereas the tensile strength was in the order of aq < HF < FA. Further, the results of the annealing process indicated notable changes in morpho-topographical, physical, degradation, and tensile properties. However, the films showed no detectable changes in chemical composition and remained optically clear with >90% transmission in the visible range, irrespective of fabrication and postfabrication processing conditions. The films were noncytotoxic against L929 cells and were cytocompatible with rabbit cornea-derived SIRC cells in vitro. The study demonstrated the potential of fine-tuning various properties of silk fibroin films by varying the fabrication and postfabrication processing conditions.

Diastereo- and regioselective petasis aryl and allyl boration of ninhydrins towards synthesis of functionalized indene-diones and dihydrobenzoindeno-oxazin-ones.

Petasis aryl and allyl borations were accomplished using substituted ninhydrins, boronic acids or 2-allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane and 1,2-aminophenols in Hexafluoroisopropanol (HFIP) without any catalysts to synthesize different aryl and allyl derivatives of ninhydrins. The nature of substitution in the boronic acids and 1,2-amino phenols was the key factor in determining the diastereo-regioselectivity and the type of product distributions. The products were isolated and characterized by HMBC, HSQC, 1H, 13C NMR experiments and X-ray single crystallographic analysis. A probable reaction pathway involves in situ formation of acyclic and cyclic ninhydrin-amino alcohol adducts, with the positioned hydroxyl group determining the stereo-regioselective outcome via tetracoordinated boron intermediates. A metal free diastereo- and regioselective Petasis aryl and allyl boration of ninhydrins.

Metal- and Additive-Free Intermolecular Aziridination of Olefins Using N-Boc-O-tosylhydroxylamine

AbstractA metal and additive-free stereospecific direct N-H and N-Me aziridination of inactivated olefins is disclosed using N-Boc-O-tosyl­hydroxylamine (TsONHBoc) as an aminating agent in hexafluoroisopropanol (HFIP). The use of TsONHBoc, which generates the free aminating agent in situ under the reaction conditions, has several inherent advantages over other similar agents, such as low cost, easy access, and stability (non-explosiveness) during storage over a longer time.

Photoredox-catalyst-controlled divergent alkylation of α-CF3-olefins

In this issue of Chem Catalysis , Shen and coworkers report a photoredox-catalyzed divergent radical alkylation of α-CF 3 -olefins through a juidicious choice of photocatalysts with suitable reduction potentials, delivering a series of gem -difluoroalkenes and trifluoromethyl alkanes from α-CF 3 olefins. The use of hexafluoroisopropanol (HFIP) as an additive is important to the selective construction of trifluoromethyl alkanes. In this issue of Chem Catalysis , Shen and coworkers report a photoredox-catalyzed divergent radical alkylation of α-CF 3 -olefins through a juidicious choice of photocatalysts with suitable reduction potentials, delivering a series of gem -difluoroalkenes and trifluoromethyl alkanes from α-CF 3 olefins. The use of hexafluoroisopropanol (HFIP) as an additive is important to the selective construction of trifluoromethyl alkanes.

Plasma Etching of SiO2 Contact Holes Using Hexafluoroisopropanol and C4F8

This study presents the feasibility of the use of hexafluoroisopropanol (HFIP) as a substitute to perfluorocarbon (PFC) for the plasma etching of SiO2 to confront the continuous increase in demand for PFC emission reduction. SiO2 etching is conducted in HFIP/Ar and C4F8/Ar plasmas, respectively, and its characteristics are compared. The SiO2 etch rates in the HFIP/Ar plasma are higher compared with those in the C4F8/Ar plasma. The thickness of the steady-state fluorocarbon films formed on the surface of SiO2 are lower in the HFIP/Ar plasma compared with in the C4F8/Ar plasma. Higher SiO2 etch rates and thinner fluorocarbon films in the HFIP/Ar plasma are attributed to the oxygen atoms in HFIP, which generate oxygen radicals that react with the fluorocarbon films to turn into volatile products. Due to the higher dissociation of C-F bonds in CF4 compared with in HFIP, the etch rates of SiO2 in the C4F8/Ar plasma increase more rapidly with the magnitude of the bias voltage compared with those in the HFIP/Ar plasma. The etch profiles of the 200 nm diameter SiO2 contact holes with an aspect ratio of 12 show that fairly anisotropic SiO2 contact hole etching was achieved successfully using the HFIP/Ar plasma.

Improving mechanical properties and biodegradation of polyvinyl alcohol material using poly(D,L-lactic acid-co-glycolic acid)

ABSTRACT Green polyvinyl alcohol/poly(D,L-lactide-co-glycolide) (PVA/PLGA) composite materials were developed by dissolving PVA and PLGA in hexafluoroisopropanol (HFIP), followed by the subsequent layout of PVA/PLGA/HFIP liquid film and the removal of HFIP. Interestingly, the PVA/PLGA composite materials display remarkedly enhanced tensile strength, elongation at break, biodegradability and biocompatibility. Systematic investigations have been completed to reveal the effects of PVA/PLGA mass ratio on the tensile strength, elongation at break, biodegradability and biocompatibility. Meanwhile, the morphology, crystallinity and chemical structure of the PVA/PLGA material and possible interaction between PVA and PLGA are also investigated using scanning electron micrograph, infrared spectra and X-ray diffraction techniques.

Palladium-Catalyzed Regioselective B(9)-Amination of o-Carboranes and m-Carboranes in HFIP with Broad Nitrogen Sources.

Amination of carboranes has a good application prospect in organic and pharmaceutical synthesis. However, the current methods used for this transformation suffer from limitations. Herein, we report a practical method for a highly regioselective formation of a B-N bond by Pd(II)-catalyzed B(9)-H amination of o- and m-carboranes in hexafluoroisopropanol (HFIP) with different nitrogen sources under air atmosphere. The silver salt and HFIP solvent play critical roles in the present protocol. The mechanistic study reveals that the silver salt acts as a Lewis acid to promote the electrophilic palladation step by forming a heterobimetallic active catalyst PdAg(OAc)3; the strong hydrogen-bond-donating ability and low nucleophilicity of HFIP enhance the electrophilic ability of Pd(II). It is believed that these N-containing carboranes are potentially of great importance in the synthesis of new pharmaceuticals.

Pulse-field gradient nuclear magnetic resonance of protein translational diffusion from native to non-native states.

Hydrodynamic radii (Rh -values) calculated from diffusion coefficients measured by pulse-field-gradient nuclear magnetic resonance are compared for folded and unfolded proteins. For native globular proteins, the Rh -values increase as a power of 0.35 with molecular size, close to the scaling factor of 0.33 predicted from polymer theory. Unfolded proteins were studied under four sets of conditions: in the absence of denaturants, in the presence of 6M urea, in 95% dimethyl sulfoxide (DMSO), and in 40% hexafluoroisopropanol (HFIP). Scaling factors under all four unfolding conditions are similar (0.49-0.53) approaching the theoretical value of 0.60 for a fully unfolded random coil. Persistence lengths are also similar, except smaller in 95% DMSO, suggesting that the polypeptides are more disordered on a local scale with this solvent. Three of the proteins in our unfolded set have an asymmetric sequence-distribution of charged residues. While these proteins behave normally in water and 6M urea, they give atypically low Rh -values in 40% HFIP and 95% DMSO suggesting they are forming electrostatic hairpins, favored by their asymmetric sequence charge distribution and the low dielectric constants of DMSO and HFIP. While diffusion-ordered NMR spectroscopy can separate small molecules, we show a number of factors combine to make protein-sized molecules much more difficult to resolve in mixtures. Finally, we look at the temperature dependence of apparent diffusion coefficients. Small molecules show a linear temperature response, while large proteins show abnormally large apparent diffusion coefficients at high temperatures due to convection, suggesting diffusion reference standards are only useful near 25°C.

Three-Component Friedel-Crafts Transformations: Synthesis of Alkyl and Alkenyl Trifluoromethyl Sulfides and Alkenyl Iodides.

Straightforward and mild hexafluoroisopropanol (HFIP)-mediated, metal-free, three-component Friedel-Crafts approaches are reported for the synthesis of alkenyl and alkyl trifluoromethyl sulfides from arenes, (PhSO2)2NSCF3, and alkynes or alkenes, respectively. The transformations proceed with high regio- and stereochemical control via the initial formation of cationic thiirenium and thiiranium intermediates, respectively, followed by Friedel-Crafts reactions with the arene. A mechanistically related three-component synthesis of alkenyl iodides from arenes, alkenes, and N-iodosuccinimide is also reported.