Synthesis of purines and adenines containing the hexafluoroisopropyl group.

Several new derivatives of adenine, purine, and theophylline containing the (CF3)2CH group connected to a nitrogen atom of the imidazole ring were prepared by the reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (1) with the corresponding substrates, resulting in the selective alkylation of one of the nitrogen atoms of the imidazole ring. The reaction proceeds under mild conditions in a polar solvent, giving the alkylated products in 47-78% yield. While for purine and 4- and 5-azabenzimidazole, the reaction led to a mixture of two isomers, the reaction of adenine and the corresponding 2-fluoro derivative was regioselective, resulting in the formation of only one isomer in each case. The alkylation of theophylline led to the formation of a new derivative of caffeine.

Diels-Alder reactions of "in situ" generated perfluorinated thioketones.

A simple and general procedure for the preparation of Diels-Alder adducts of perfluorinated thioketones and various dienes is reported. The corresponding Diels-Alder adducts were prepared in 30-78% yield under mild conditions via a reaction of a mixture of fluoroolefins, sulfur, diene and CsF as a catalyst.

Broadband 19F TOCSY using BURBOP-based spin lock.

A train of BURBOP universal rotation pulses has been used to generate a spin lock sufficient to observe TOCSY correlations over a 46 kHz 19F spectral window (i.e. 122 ppm on a 9.4 T spectrometer). This spin lock requires lower RF field (γB1 = 15 kHz), and was employed over a wider spectral window, than previously reported DIPSI-2 spin locks. The BURBOP-based spin lock was effected for 80-160 ms periods with a 2% duty cycle without evidence of harm to the RF coil of the probehead. Spectral separation and full set of correlations were obtained for a mixture of perfluorocarbons.

Comparison of 1H-19F two-dimensional NMR scalar coupling correlation pulse sequences.

The effectiveness of hetero-COSY, HETCOR, HMQC, and HSQC two-dimensional NMR pulse sequences for detection of (19)F-(1)H correlations by scalar coupling was evaluated on monofluorinated and polyfluorinated test compounds. All four of these sequences were effective in observing (1)H-(19)F correlations, using either (19) F or (1)H as the observe nucleus. All four sequences were amenable, to some degree, to adjustment to observe larger or smaller couplings preferentially. A 1/2J echo filter was effectively applied to remove artifacts from (2)JFF strong coupling. The HETCOR experiments afforded the best overall combination of sensitivity, resolution and selectivity for JHF.

Discrimination of pseudo-meta and pseudo-para diamino-octafluoro[2.2]paracyclophanes by (1)H, (19)F, and (13)C NMR.

Pseudo-meta and pseudo-para diamino-octafluoro[2.2]paracyclophanes are challenging to separate either by chromatography or recrystallization, but through the use of a mixture of the two isomers, the (1)H, (19)F, and (13)C NMR spectra of these compounds have been fully and unambiguously assigned using (1)H COSY, (1)H-(19)F HOESY, (1)H-(13)C HSQC, (1)H-(13)C HMBC, and (19)F-(13)C HSQC techniques. This permits the easy identification of either of the individual isomers. In addition, the (13)C spectrum of the pseudo-ortho analogue is reported and assigned for the first time. The gem shift effect in this series of bridge-fluorinated paracyclophanes serves to deshield (1)H resonances and shield (13)C.

Two-dimensional NMR correlation experiments in the gas phase.

The application of common two-dimensional NMR correlation experiments to gaseous analytes for structural elucidation is reported. Standard sequences such as COSY, HSQC, and HMBC are readily applied to volatile hydrocarbons and fluorocarbons. In experiments using (19)F or (13)C as the observed nucleus, it is possible to take advantage of efficient spin-rotation relaxation to perform common experiments swiftly (a (19)F COSY acquired in 6s is shown) or to render insensitive experiments possible on a practical timescale (e.g. a gas phase INADEQUATE at natural isotopic abundance in 14h). NOE-based experiments were not successful on the gaseous systems studied.

Spectral separation of gaseous fluorocarbon mixtures and measurement of diffusion constants by 19F gas phase DOSY NMR.

Diffusion-ordered (DOSY) NMR techniques have for the first time been applied to the spectral separation of mixtures of fluorinated gases by diffusion rates. A mixture of linear perfluoroalkanes from methane to hexane was readily separated at 25 degrees C in an ordinary experimental setup with standard DOSY pulse sequences. Partial separation of variously fluorinated ethanes was also achieved. The constants of self-diffusion of a set of pure perfluoroalkanes were obtained at pressures from 0.25 to 1.34 atm and temperatures from 20 to 122 degrees C. Under all conditions there was agreement within 20% of experimental self-diffusion constant D and values calculated by the semiempirical Fuller method.

Investigation of the correlations between (19)F and (1)H NMR signals for various mono- and di-substituted octafluoro[2.2]paracyclophanes.

A selection of mono- and pseudo ortho di-substituted octafluoro[2.2]paracyclophane derivatives were analyzed using (19)F-(1)H HOESY, (1)H COSY and (19)F COSY techniques. This resulted in the unambiguous assignment of the (19)F and (1)H NMR resonances, and also revealed interesting solvent effects and noteworthy coupling patterns for various J(HH), J(HF), and J(FF) interactions, including observable through bond (7)J(FF) and (8)J(FF) couplings. For the four mono-substituted derivatives, the assignments were achieved through the combination of (19)F-(1)H HOESY, (1)H COSY and (19)F COSY techniques. The C(2) symmetry of the six pseudo ortho di-substituted derivatives that were examined produced simplified spectra, and careful inspection of the characteristic (1)H coupling patterns led to the assignment of (1)H signals. Therefore only (19)F-(1)H HOESY experiments were required to complete the assignments for those molecules. Refinements and alternative strategies for previous protocols are presented for the molecules that were less responsive to nuclear Overhauser effect (nOe) experiments.

Complete multinuclear magnetic resonance characterization of a set of polyfluorinated acids and alcohols.

A complete (1)H, (19)F, and (13)C NMR assignment of a homologous series of polyfluorinated acids and alcohols is reported. These assignments were obtained chiefly through single and multiple-bond (1)H-(13)C and (19)F-(13)C correlation experiments (HSQC, HMBC). (19)F NOESY experiments were required for assignment of two compounds with diastereotopic (19)F nuclei in the CF(2)chain of the molecule.

Estimation of atmospheric lifetimes of hydrofluorocarbons, hydrofluoroethers, and olefins by chlorine photolysis using gas-phase NMR spectroscopy.

An empirical correlation has been derived between accepted atmospheric lifetimes of a set of hydrofluorocarbons and hydrofluoroethers and relative rates of reaction with photolyzed chlorine in excess at ambient temperature. These kinetic systems were studied by nuclear magnetic resonance (NMR) spectroscopy in the gas phase, marking the first application of NMR spectroscopy to this field. The square of the Pearson coefficient R for the linear correlation between observed reaction rates and accepted atmospheric lifetimes was 0.87 for compounds of lifetime less than 20 years. The method was extended to the study of ethene and propene; the rate of reaction of propene was found to be 1.25 times that of ethene at 23 degrees C. The chief advantage of this method is its simplicity and reliance only on common tools and techniques of an industrial chemical laboratory.

Comparative pulmonary toxicity assessments of C60 water suspensions in rats: few differences in fullerene toxicity in vivo in contrast to in vitro profiles.

It has previously been reported that the in vitro cytotoxic effects of water-soluble fullerene species are a sensitive function of their surface derivatization status. In a recent study, it was reported that doses of an aggregated form of underivatized C60, termed nano-C60, were 3-4 orders of magnitude more toxic to human dermal fibroblasts, lung epithelial cells, and normal human astrocytes when compared to identical exposures of these cell types to a fully derivatized, highly water-soluble derivative, C60(OH)24. Accordingly, the aim of this study was to test and validate these in vitro findings by comparing the in vivo pulmonary toxicity effects in rats of intratracheally instilled nano-C60 and C60(OH)24. In two combined studies, groups of rats were instilled with doses of either 0.2, 0.4, 1.5, or 3.0 mg/kg of nano-C60, C60(OH)24, or alpha-quartz particle types using Milli-Q water as the vehicle. Subsequently, the lungs of vehicle and particle-exposed rats were assessed using bronchoalveolar lavage (BAL) fluid biomarkers, oxidant and glutathione endpoints, airway and lung parenchymal cell proliferation methods, and histopathological evaluation of lung tissue at 1 day, 1 week, 1 month, and 3 months postinstillation exposure. Exposures to both nano-C60 or water-soluble C60(OH)24 produced only transient inflammatory and cell injury effects at 1 day postexposure (pe) and were not different from water instilled controls at any other pe time periods. An increase in lipid peroxidation endpoints vs controls was measured in BAL fluids of rats exposed to 1.5 and 3 mg/kg of nano-C60 at 1 day and 3 month pe time points. In addition, no adverse lung tissue effects were measured at 3 months postinstillation exposures to the highest dose of the two types of fullerenes. In contrast, pulmonary exposures to quartz particles in rats produced dose-dependent lung inflammatory responses characterized by neutrophils and foamy lipid-containing alveolar macrophage accumulation as well as evidence of early lung tissue thickening consistent with the development of pulmonary fibrosis. The results demonstrated little or no difference in lung toxicity effects between the two fullerene samples when compared to controls, and these data are not consistent with the previously reported in vitro effects. The findings exemplify both the difficulty in interpreting and extrapolating in vitro toxicity measurements to in vivo effects and highlight the complexities associated with probing the relevant toxicological responses of fullerene nanoparticle systems.

Full multinuclear resonance analysis of 4-amino-1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane.

The complete assignment of 19F, 1H and 13C NMR spectra for a monosubstituted octafluoro[2.2]paracyclophane derivative is described for the first time. The unambiguous assignments were achieved through the combination of 19F--1H HOESY, 1H COSY and 19F COSY techniques and then further confirmed employing a complementary approach using a Karplus-dependent 3JCF interaction. Interesting aspects of the coupling patterns for various JHH, JHF, JCF and JFF interactions are also discussed.

Vapor pressure and intramolecular hydrogen bonding in fluorotelomer alcohols.

Vapor pressure and aqueous solubility are important parameters used to estimate the potential for transport of chemical substances in the atmosphere. For fluorotelomer alcohols (FTOHs), currently under scrutiny by environmental scientists as potential precursors of persistent perfluorocarboxylates (PFCAs), vapor pressure is the more significant property since these compounds are only very sparingly soluble in water. We have measured the vapor pressures of a homologous series of fluorotelomer alcohols, F(CF2CF2)nCH2CH2OH (n = 2-5), in the temperature range 21-250 degrees C by three independent methods: (a) a method suitable for very low vapor pressures at ambient temperatures (gas-saturation method), (b) an improved boiling point method at controlled pressures (Scott method), and (c) a novel method, requiring milligram quantities of substance, based on gas-phase NMR, a technique largely unfamiliar to chemists and holding promise for studies of relevance to environmental chemistry. The concordant values obtained indicate that recently published vapor pressure data overestimate the vapor pressure at ambient temperature, and therefore the volatility, of this series of fluorinated compounds. It was suggested that substantial intramolecular -O-H...F- hydrogen bonding between the hydroxylic proton and the two fluorines next to the ethanol moiety was responsible for their putative high volatility. Therefore, we have used gas-phase NMR, gas-phase FTIR, 2D NMR heteronuclear Overhauser effect measurements, and high-level ab initio computations to investigate the intramolecular hydrogen bonding in fluorotelomer alcohols. Our studies unequivocally show that hydrogen bonding of this type is not significant and cannot contribute to and cause unusual volatility. The substantially lower vapor pressure at ambient temperatures than previously reported resulting from our work is important in developing a valid understanding of the environmental transport behavior of this class of compounds.