Fluoroalkene chemistry: Part 3. Reactions of arylthiols with perfluoroisobutene, perfluoropropene and chlorotrifluoroethene

Reactions of perfluoroisobutene (PFIB), perfluoropropene (PFP) and chlorotrifluoroethene (CTFE) with benzenethiol and 2-methoxybenzenethiol in acetonitrile, with potassium carbonate as base, were compared. PFIB reacted with benzenethiol to give ketene thioacetal (CF₃)₂CC(SAr)₂ and with 2-methoxybenzenethiol to give mono- and bis-vinyl species (CF₃)₂CCFSAr and (CF₃)₂CC(SAr)₂. PFP reacted with both thiols to give the addition product CF₃CFHCF₂SAr and vinyl isomers CF₃CFCFSAr (6:1 E/Z ratio). CTFE reacted with several methoxy-substituted arylthiols to give addition products of structure CFClHCF₂SAr. The arylthiols used throughout the study imitate biological thiols. Inhalation toxicities of the fluoroalkenes decrease in the order PFIB > PFP > CTFE and correlate with their reactivities towards the model thiols, supporting the current view that their toxicity relates to their ability to react with biological thiols.     

Langmuir-Blodgett thin films of quantum dots: synthesis, surface modification, and fluorescence resonance energy transfer (FRET) studies

We describe herein studies on as-prepared hydrophobic ZnS-CdSe quantum dots (QDs) at the air-water interface. Surface pressure-area (pi-A) isotherms have been used to study the monolayer behavior. Uniform, lamellar multilayer thin films of QDs were deposited by the Langmuir-Blodgett (LB) technique. The role of two different surfactant systems commonly employed in the synthesis of these QDs (trioctylphosphine oxide-octadecylamine (TOPO-ODA) system and trioctylphosphine oxide-tetradecylphosphonic acid (TOPO-TDPA) system) on the monolayer behavior and the quality of thin films produced has been investigated. The thin films were characterized by quartz crystal microgravimetry (QCM), contact angle measurements, fluorescence spectroscopy, and transmission electron microscopy (TEM). These QD films were further modified by an amphiphilic polymer, poly(maleic anhydride-alt-1-tetradecene) (PMA). The hydrophobic interaction between the polymers and the surfactants attached to the QDs drove the self-assembly process. The carboxylic acid functional groups in the polymer were also used to immobilize avidin. We have demonstrated a proof of concept for the biosensing strategy wherein the avidin-coated QD films attracted biotinylated gold nanoparticles, resulting in fluorescence resonance energy transfer (FRET) quenching of the thin films.     

Facile synthesis of unsymmetrical 9-phospha- and 9-arsafluorenes

Unsymmetrical 9-chloro-9-phosphafluorenes (dibenzophospholes) and 9-chloro-9-arsafluorenes (dibenzoarsoles) have been obtained by simple thermolysis of m-terphenyldichlorophosphines and -arsines in close to quantitative yields. The reaction temperatures are about 200 degrees C for the phosphines and 140 degrees C for the arsine, and the reactions are complete within 5 min. Alternatively, these compounds can be synthesized through an AlCl3-catalyzed Friedel-Crafts type ring-closure reaction at low temperatures, but this method suffers from difficult workup procedures. The P(As)-Cl functionality is readily alkylated. Methylation of m-xylyl derivative 4 afforded 1-(3,5-dimethylphenyl)-6,8,9-trimethyl-9-phosphafluorene, 11. The latter compound formed the complexes 11 x Fe(CO)4, 12, and 11 x RuCl2(eta(6)-p-cymene), 13, indicating its good donor properties. The new compounds have been characterized by 1H, 13C{1H}, and 31P{1H} NMR spectroscopy; mass spectrometry; and single-crystal X-ray crystallography in the case of 11, 12, and 13.     

Using Electron Induced Dissociation (EID) on an LC Time-Scale to Characterize a Mixture of Analogous Small Organic Molecules

LC ESI FTICR MS of a sample of cediranib identified this pharmaceutical target molecule plus an additional 10 compounds of interest, all of which were less than 10% total ion current (TIC) peak intensity relative to cediranib. LC FTICR tandem mass spectrometry using electron induced dissociation (EID) has been achieved and has proven to be the best way to generate useful product ion information for all of these singly protonated molecules. Cediranib [M + H]⁺ fragmented by EID to give 29 product ions whereas QTOF-CID generated only one very intense product ion, and linear ion trap-CID, which generated 10 product ions, but all with poor S/N. Twenty-six of the EID product ions were unique to this fragmentation technique alone. By considering the complementary LC-EID and LC-CID data together, all 10 unknown compounds were structurally characterized and proven to be analogous to cediranib. Of particular importance, EID produced unique product ion information for one of the low level cediranib analogues that enabled full characterization of the molecule such that the presence of an extra propylpyrrolidine group was discovered and proven to be located on the pyrrolidine ring of cediranib, solving an analytical problem that could not be solved by collision induced dissociation (CID). Thus, it has been demonstrated that EID is in harmony with the chromatography duty-cycle and the dynamic concentration range of synthetic compounds containing trace impurities, providing crucial analytical information that cannot be obtained by more traditional methodologies.     

Removal of exogenously bound elements from human hair by various washing procedures and determination by inductively coupled plasma mass spectrometry

A review of the literature shows that a variety of washing procedures to remove external contamination from hair have been proposed, but as yet no standardised procedures are available. In this study, methods for the pre-treatment and determination of antimony, arsenic, cadmium, chromium, lead, mercury and selenium in human hair by inductively coupled plasma mass spectrometry (ICP-MS) are developed.Investigations of various washing procedures to remove external contaminants show that in unexposed hair samples cadmium, lead and mercury are significantly removed from hair using a 0.1 M HCl wash, with 87, 73 and 5%, respectively being washed-off. The removal of antimony, arsenic and chromium from unexposed hair is, however, more efficient with 1% (v/v) sodium lauryl sulphate (SLS), with 43, 40 and 13% of each element, respectively being washed-off. Selenium is not removed from the hair by any of the washing methods studied. For the digestion of hair samples a digestion mixture of nitric acid and hydrogen peroxide is used.Experiments with simulated sweat spiked with each of these elements show that exogenously bound chromium, cadmium and lead are removed after washing with 0.1 M HCl. In contrast, antimony, arsenic, selenium and mercury irreversibly bind and, thus, are not removed with any of the washing solutions investigated. This work also compares hair levels of these elements in an unexposed and exposed group using the method developed.     

Lysozyme purification from tobacco extract by polyelectrolyte precipitation

Tobacco is widely used as a model plant for feasibility studies of recombinant protein production from transgenic plants. However, dealing with large quantities of biomass to recover recombinant proteins is a challenge for down-stream processing. In this study, the effect of isoelectric precipitation on native tobacco protein was first studied. Among the three acids studied, hydrochloric acid is shown to be more effective than acetic or citric acid, and at pH 4, 60% of native tobacco protein was precipitated by HCl. Egg white lysozyme was used as the model protein to test the feasibility of polyelectrolyte precipitation in protein recovery from tobacco extract. Precipitation of lysozyme at pH 7 was shown ineffective probably because of the interference of polyphenolic acids. However, after isoelectric precipitation at pH 5 poly(acrylic) acid (PAA) was shown to precipitate 85% of the soluble lysozyme when the polymer dosage was increased to 1.5 mg polymer/mg lysozyme, while negligible amounts of native tobacco protein was co-precipitated. Lysozyme precipitation by PAA in tobacco extract obtained at pH 5 was also studied, and lysozyme yield was significant improved.     

Semidefinite diagonal directions Monte Carlo algorithms for detecting necessary linear matrix inequality constraints

Hit-and-run algorithms are Monte Carlo methods for detecting necessary constraints in convex programming including semidefinite programming. The well known of these in semidefinite programming are semidefinite coordinate directions (SCD), semidefinite hypersphere directions (SHD) and semidefinite stand-and-hit (SSH) algorithms. SCD is considered to be the best on average and hence we use it for comparison.We develop two new hit-and-run algorithms in semidefinite programming that use diagonal directions. They are the uniform semidefinite diagonal directions (uniform SDD) and the original semidefinite diagonal directions (original SDD) algorithms. We analyze the costs and benefits of this change in comparison with SCD. We also show that both uniform SDD and original SDD generate points that are asymptotically uniform in the interior of the feasible region defined by the constraints.     

Odor Provocation Test for Laryngeal Hypersensitivity

This study was to present an odor provocation/challenge test for laryngeal hypersensitivity in a suspected odor induced dysphonic patient. The second aim was to rule out secondary gain from organic laryngeal hypersensitivity. Two steps were taken for this purpose. First, because the evaluation of hypersensitivity may be affected by the perception of odor, the study investigated laryngeal hypersensitivity during nasal and oral breathing separately to disentangle possible cognitive reactions to odors. Second, a healthy control (HC) participant was used with the identical testing protocol for nasal breathing to minimize unbiased results. The HC's response to nasal breathing of the odors showed no response to all the stimuli. The participant with possible secondary gain issues responded differently to the odors when presented nasally versus orally. Oral breathing showed less severe and less frequent laryngeal hypersensitive reactions. This suggests that laryngeal hypersensitivity was either due to the odor, cognitive information, sensory changes in olfaction leading to psychological conditioning, or for any possible secondary gain. Hence, it is difficult to indicate the precise reason (cause and effect) for the participant's laryngeal hypersensitivity; however, this study describes the first structured, controlled, repeatable, and randomized design to investigate odor induced laryngeal hypersensitivity and decipher possible secondary gain from true laryngeal hypersensitivity.