Metabolite profiling in rat urine by liquid chromatography/electrospray ion trap mass spectrometry. Application to the study of heavy metal toxicity

This work reports the use of reverse-phase liquid chromatography coupled to electrospray ion trap (QIT) mass spectrometry for the analysis of the metabolome in rat urine. An injection of 20 microL of urine into the chromatographic system is followed by a slow gradient elution and mass spectrometric detection in the scanning mode from m/z 100-1000 in both positive and negative modes. Over a time scale of 90 min, 30 and 20 resolved peaks were observed in the positive and the negative modes, respectively, corresponding to the presence of a few hundred m/z ratios. By using a QIT analyzer, data-dependent tandem mass spectrometry of selected m/z ratios identified several compounds in rat urine and characterized various chemical families, including carboxylic acids, amines, sulfated compounds, glucuronides and glycosides, by the observation of characteristic fragment ions or neutral losses. The method has been applied to the investigation of the chronic toxicity of heavy metals in rat urine. A few tens of m/z ratios, differing in intensity more than threefold from control values, were observed in both positive and negative modes. The time variations for some selected ions suggest that LC/ESI-MS could allow selective characterization of biomarkers in response to specific toxic compounds.     

Tetrakis(diethyl‐phosphonat)‐, Tetrakis(ethyl‐phenylphosphinat)‐ und Tetrakis(diphenylphosphin‐oxid)‐substituierte Phthalocyanine

Tetrakis(diethyl phosphonate), Tetrakis(ethyl phenylphosphinate)‐, and Tetrakis(diphenylphosphine oxide)‐Substituted Phthalocyanines The title compounds 7, 9 , and 11 are obtained by tetramerization of diethyl (3,4‐dicyanophenyl)phosphonate ( 5 ), ethyl (3,4‐dicyanophenyl)phenylphosphinate ( 8 ), and 4‐(diphenylphosphinyl)benzene‐1,2‐dicarbonitrile ( 10 ). The ³¹P‐NMR spectra of the phthalocyanines 7, 9 , and 11 and of their metal complexes present five to eight signals confirming the formation of four constitutional isomers with the expected C_4h, D_2h, C_2v, and C_s symmetry. In the FAB‐MS of the Zn, Cu, and Ni complexes of 7 and 9 , the peaks of dimeric phthalocyanines are observed. By gel‐permeation chromatography, the monomeric complex [Ni( 7 )] and a dimer [Ni( 7 )]₂ can be separated. These dimers differ from the known phthalocyanine dimers, i.e., possibly the P(O)(OEt)₂ and P(O)(Ph)(OEt) substituents in 7 and 9 are involved in complexation. The free phosphonic acid complex [Zn( 12 )] and [Cu( 12 )] are H₂O‐soluble. In the FAB‐MS of [Zn( 12 )], only the peaks of the dimer are present; the ESI‐MS confirms the existence of the dimer and the metal‐free dimer. In the UV/VIS spectrum of [Zn( 12 )], the hypsochromic shift characteristic for the known type of dimers from 660–700 nm to 620–640 nm is observed. As in the FAB‐MS of [Zn( 12 )], the free phosphinic acid complex [Zn( 13 )] shows only the monomer, an ESI‐MS cannot be obtained for solubility problems. The UV/VIS spectrum of [Zn( 13 )] demonstrates the existence of the monomer as well as of the dimer.     

Carbazole compounds as host materials for triplet emitters in organic light-emitting diodes: polymer hosts for high-efficiency light-emitting diodes

A carbazole homopolymer and carbazole copolymers based on 9,9'-dialkyl-[3,3']-bicarbazolyl, 2,5-diphenyl-[1,3,4]-oxadiazole and 9,9-bis(4-[3,7-dimethyloctyloxy]phenyl)fluorene were synthesized and their electrical and photophysical properties were characterized with respect to their application as host in phosphorescent polymer light-emitting diodes. It is shown that the triplet energy of a polymer depends on the specific connections between its building blocks. Without changing the composition of the polymer, its triplet energy can be increased from 2.3 to 2.6 eV by changing the way in which the different building blocks are coupled together. For poly(9-vinylcarbazole) (PVK), a carbazole polymer often used as host for high-energy triplet emitters in polymer light-emitting diodes, a large hole-injection barrier of about 1 eV exists due to the low-lying HOMO level of PVK. For all carbazole polymers presented here, the HOMO levels are much closer to the Fermi level of a commonly used anode such as ITO and/or a commonly used hole-injection layer such as PEDOT:PSS. This makes high current densities and consequently high luminance levels possible at moderate applied voltages in polymer light-emitting diodes. A double-layer polymer light-emitting diode is constructed comprising a PEDOT:PSS layer as hole-injection layer and a carbazole-oxadiazole copolymer doped with a green triplet emitter as emissive layer that shows an efficacy of 23 cd/A independent of current density and light output.     

Hydrogen Bonding in Pyridine N-Oxide/Acid Systems: Proton Transfer and Fine Details Revealed by FTIR, NMR, and X-ray Diffraction

The H-bonded complexes of pyridine N-oxide (PyO) with H(2)O, acetic, cyanoacetic, propiolic, tribromoacetic, trichloroacetic, trifluoroacetic, hydrochloric, and methanesulfonic acids have been studied by FTIR and NMR spectroscopy, X-ray diffraction, and quantum chemical DFT calculations. Correlations between vibrational frequencies of the NO stretching and PyO ring modes and geometric parameters of the H-bond have been established. FTIR experiments show and DFT calculations confirm that definite discontinuity is present in the vicinity of the midpoint in the proton transfer pathway. The established correlations significantly aid in the understanding of fine effects such as the isotope (deuteration) effect, crystal-to-solution transition, or criticality of aqueous solutions induced by ionic pairs. Geometric isotope effect in the ionic H-bond aggregate of PyO·H(D)Cl was found to be extraordinary large. Measured FTIR, CP/MAS, and high-resolution (13)C NMR spectra indicate that H-bond in the PyO·HCl complex in polar solvent can potentially be more ionic than in the crystal. Vibrational modes of ionic pairs originating via proton transfer in H-bond complexes can provide new information concerning the interionic interaction and its role in the phase separation and mezo-structuring processes. The results are compared to the relevant data for PyO·HCl complex in argon matrix.     

Enolethers. XXI. Synthesis of 5,5′-disubstituted 4,4′-bipyrimidines

1,6-Dialkoxy-3,4-diones 3 are easily accessible by acylation of enol ethers 1 with oxalyl chloride and subsequent elimination of hydrogen chloride using triethylamine. The open-chain 2,5-dimethyl derivative 3b is converted with amidines 4a-c and S-methylisothiourea (4d) , respectively, to give 2,2′-disubstituted 5,5′-dimethyl-4,4′-bipyrimidines 5a-d . The dihydrofuran and dihydropyran derivatives 3c and 3d , however, react with benzamidine (4c) in dimethylformamide only in the presence of calcium hydride as condensation agent yielding 5,5′-bis(2-hydroxyethyl)- and 5,5′-bis(3-hydroxypropyl)-2,2′-diphenyl-4,4′-bipyrimidine 6a and b.     

(Z)-1-[2-(Triarylstannyl)vinyl]-1-cycloheptanols: Synthesis, characterization, halodemetallation and crystal structures

The synthesis and characterization by ¹H, ¹³C, ¹¹⁹Sn NMR and ¹¹⁹Sn Mössbauer spectroscopy of (Z)-1-[2-(triphenylstannyl)vinyl]-1-cycloheptanol,

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(1), and (Z)-1-[2-tri-p-tolylstannyl)vinyl-1-cycloheptanol,

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(2), are described, together with their halodemetallation by I₂, Br₂ and ICIl to yield derivatives of the types

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(Ar = phenyl or p-tolyl, N = 1, 2; X = I, Br, Cl, respectively). The solid-state structures of four compounds have been determined by X-ray diffraction analysis. In the crystals of

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(1) and

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(2) the Sn atom has a tetrahedral geometry distorted towards trigonal bipyramid as a consequence of a close intramolecular contact with the hydroxyl O(1) atom of 2.742(3) Å and 2.768(3) Å, respectively. A trigonal bipyramidal geometry is found in

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(12) and

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(4), in which significant Sn---O(1) interactions are noted [2.437(8) Å and 2.407(8) Å, respectively].     

Hexaphenylbenzene-based polymers of intrinsic microporosity

Microporous polymers derived from the 1,2- and 1,4-regioisomers of di(3',4'-dihydroxyphenyl)tetraphenylbenzene have very different properties with the former being composed predominantly of cyclic oligomers whereas the latter is of high molar mass suitable for the formation of robust solvent-cast films of high gas permeability.     

Novel polyesteramide-based di- and triblock copolymers: From thermo-mechanical properties to hydrolytic degradation

Two types of biodegradable poly(ε-caprolactone (CLo))-co-poly(ε-caprolactam (CLa)) copolymers were prepared by catalyzed hydrolytic ring-opening polymerization. For the first type of materials, the respective cyclic comonomers were added simultaneously in the reaction medium leading to the formation of copolymers having a random distribution of co-units within the polyesteramide sequence, as evidenced by ¹H and ¹³C NMR. For the second type of copolymers, the cyclic comonomers were added sequentially in the reaction medium yielding diblock polyesteramides, again evidenced by NMR. The thermal and thermo-mechanical properties of the copolymers were investigated by DSC and DMA and correlated with the copolymer topology and composition. The copolymers were characterized by a storage modulus and α transition temperature intermediate to the modulus and T_g of the corresponding homopolymers. The chemical composition and molecular weight of the copolymers proved to have only a limited effect on the thermo-mechanical properties of the materials. The hydrolytic degradation of random copolymers was studied in a phosphate buffer at 60 °C and discussed in terms of chemical composition and molecular weight of the copolymers.     

Sun Exposure over a Lifetime in Australian Adults from Latitudinally Diverse Regions

Spatio‐temporal patterns in sun exposure underlie variations in skin cancer incidence and vitamin D deficiency, indicate effectiveness of sun protection programs and provide insights into future health risks. From 558 adults across four regions of Australia (Brisbane (27°S), Newcastle (33°S), Geelong and the Western Districts of Victoria (37°S) and Tasmania (43°S)), we collected: self‐report data on time‐in‐the‐sun from age 6 years; natural skin color and ethnicity; silicone skin casts (for cumulative skin damage); and serum for vitamin D status. Ambient ultraviolet radiation (UVR) at the location of residence, with time‐in‐the‐sun, was used to calculate a “UVR dose” for each year of life. Individuals maintained their ranking compared to their peers for time‐in‐the‐sun in summer compared to winter and across ages (Spearman rho 0.24–0.84, all P < 0.001). Time‐in‐the‐sun decreased with age in all birth cohorts, and over calendar time. Summer time‐in‐the‐sun increased with increasing latitude (P < 0.001). Seasonal variation in vitamin D status had greater amplitude and vitamin D deficiency increased with increasing latitude. Temporal patterns are consistent with effectiveness of sun protection programs. Higher relative time‐in‐the‐sun persists from childhood through adulthood. Lower summer time‐in‐the‐sun in the warmest location may have implications for predictions of UVR‐related health risks of climate change.