Symmetric Mixed Sulfur-Selenium Fused Ring Systems as Potential Materials for Organic Field-Effect Transistors.

A reliable synthetic protocol toward a series of fused chalcogenopheno[1]benzochalcogenophene (CBC) building blocks was developed based on a Fiesselmann reaction. The obtained CBC units were applied in McMurry and Stille coupling reactions toward symmetric regioisomeric ene-linked dimers. These π-conjugated compounds were characterized regarding their photophysical and electrochemical properties and proved to be materials with reduced HOMO-LUMO gaps compared to their sulfur-based analogues. Single-crystal X-ray diffraction experiments revealed strong intermolecular selenium-selenium and selenium-carbon interactions depending on the position and number of incorporated selenium atoms. Good field-effect transistor performance with charge carrier mobilities up to 4×10-3  cm2 V-1 s-1 and high on/off ratios could be observed.

Thienopyrrolo[3,2,1-jk]carbazoles: Building Blocks for Functional Organic Materials.

The facile preparation of three regioisomeric thienopyrrolo[3,2,1-jk]carbazoles applying a convenient C-H activation approach is presented. The incorporation of thiophene into the triarylamine framework significantly impacted the molecular properties in comparison to the analogous indolo[3,2,1-jk]carbazole scaffold. Dependent on the exact substitution pattern, the absorption onsets of the new materials are shifted toward slightly higher wavelengths compared to the analogous indolo[3,2,1-jk]carbazole, whereas the emission maxima of the sulfur derivatives is shifted from 375 to 410 nm. In analogy, the HOMO-LUMO energy gap of the thienopyrrolo[3,2,1-jk]carbazoles is reduced compared to indolo[3,2,1-jk]carbazole. Therefore, the developed thienopyrrolo[3,2,1-jk]carbazoles enrich the family of triarylamine donors and constitute a novel building block for functional organic materials.

Azaindolo[3,2,1-jk]carbazoles: New Building Blocks for Functional Organic Materials.

The preparation and characterization of 12 azaindolo[3,2,1-jk]carbazoles is presented. Ring-closing C-H activation allowed for the convenient preparation of six singly and six doubly nitrogen-substituted indolo[3,2,1-jk]carbazole derivatives in which ten of the materials have not been described in the literature before. The detailed photophysical and electrochemical characterization of the developed materials revealed a significant impact of the incorporation of pyridine-like nitrogen into the fully planar indolo[3,2,1-jk]carbazole backbone. Furthermore, the nitrogen position decisively impacted intermolecular hydrogen bonding and thus the solid-state alignment. Ultimately, the versatility of the azaindolo[3,2,1-jk]carbazoles scaffold makes this class of materials an attractive new building block for the design of functional organic materials.

Chemical synthesis of culmorin metabolites and their biologic role in culmorin and acetyl-culmorin treated wheat cells.

The Fusarium metabolite culmorin (1) is receiving increased attention as an "emerging mycotoxin". It co-occurs with trichothecene mycotoxins and potentially influences their toxicity. Its ecological role and fate in plants is unknown. We synthesized sulfated and glucosylated culmorin conjugates as potential metabolites, which are expected to be formed in planta, and used them as reference compounds. An efficient procedure for the synthesis of culmorin sulfates was developed. Diastereo- and regioselective glucosylation of culmorin (1) was achieved by exploiting or preventing unexpected acyl transfer when using different glucosyl donors. The treatment of a wheat suspension culture with culmorin (1) revealed an in planta conversion of culmorin into culmorin-8-glucoside (6) and culmorin acetate, but no sulfates or culmorin-11-glucoside (7) was found. The treatment of wheat cells with the fungal metabolite 11-acetylculmorin (2) revealed its rapid deacetylation, but also showed the formation of 11-acetylculmorin-8-glucoside (8). These results show that plants are capable of extensively metabolizing culmorin.

Tracking emerging mycotoxins in food: development of an LC-MS/MS method for free and modified Alternaria toxins.

Mycotoxins produced by Alternaria fungi are ubiquitous food contaminants, but analytical methods for generating comprehensive exposure data are rare. We describe the development of an LC-MS/MS method covering 17 toxins for investigating the natural occurrence of free and modified Alternaria toxins in tomato sauce, sunflower seed oil, and wheat flour. Target analytes included alternariol (AOH), AOH-3-glucoside, AOH-9-glucoside, AOH-3-sulfate, alternariol monomethyl ether (AME), AME-3-glucoside, AME-3-sulfate, altenuene, isoaltenuene, tenuazonic acid (TeA), tentoxin (TEN), altertoxin I and II, alterperylenol, stemphyltoxin III, altenusin, and altenuic acid III. Extensive optimization resulted in a time- and cost-effective sample preparation protocol and a chromatographic baseline separation of included isomers. Overall, adequate limits of detection (0.03-9 ng/g) and quantitation (0.6-18 ng/g), intermediate precision (9-44%), and relative recovery values (75-100%) were achieved. However, stemphyltoxin III, AOH-3-sulfate, AME-3-sulfate, altenusin, and altenuic acid III showed recoveries in wheat flour below 70%, while their performance was stable and reproducible. Our pilot study with samples from the Austrian retail market demonstrated that tomato sauces (n = 12) contained AOH, AME, TeA, and TEN in concentrations up to 20, 4, 322, and 0.6 ng/g, while sunflower seed oil (n = 7) and wheat flour samples (n = 9) were contaminated at comparatively lower levels. Interestingly and of relevance for risk assessment, AOH-9-glucoside, discovered for the first time in naturally contaminated food items, and AME-3-sulfate were found in concentrations similar to their parent toxins. In conclusion, the established multi-analyte method proved to be fit for purpose for generating comprehensive Alternaria toxin occurrence data in different food matrices. Graphical abstract ᅟ.

A novel selenoalkenyl-isoxazole based donor-acceptor nonlinear optical material.

The structure property relationships of untwinned enantiomorphic Z-(methylseleno)alkenyl-substituted phenyl-isoxazole and its isostructural triazole congener both crystallizing in the P212121 space group were investigated with respect to UV/vis absorption, thermal behaviour, and second harmonic generation ability. Differential scanning calorimetry revealed a significantly higher melting point of the novel isoxazole compound compared to the triazole derivative and therefore a broader thermal application window. The SHG efficiency of the isoxazole derivative is approximately two thirds the value of the triazole compound and approximately 27 times higher than potassium dihydrogen phosphate. Thus, the developed molecular scaffold represents an interesting novel type of nonlinear optical (NLO) chromophore.

Chemical Glucosylation of Labile Natural Products Using a (2-Nitrophenyl)acetyl-Protected Glucosyl Acetimidate Donor.

The synthesis of (2-nitrophenyl)acetyl (NPAc)-protected glucosyl donors is described that were designed for the neighboring-group assisted glucosylation of base-labile natural products also being sensitive to hydrogenolysis. Glycosylation conditions were optimized using a trichloroacetimidate glucosyl donor, and cyclohexylmethanol and (+)-menthol as model acceptors. The approach was then extended to a one-pot procedure for the synthesis of 1,2-trans-glycosides. This method was finally applied for improved synthesis of the masked mycotoxin T2-O-ß,d-glucoside.

Color Fine-Tuning of Optical Materials Through Rational Design.

We report on the feasibility for color fine-tuning of optical materials using rational design principles based on chemical reasoning. For this purpose, a modular framework for the construction of symmetrical cap-linker-cap compounds, using triarylamine caps and oligothiophene linkers, is applied. The chosen structural scaffolds are heavily used in recent industrial applications and provide five possibilities for altering their electronic and steric properties: electron donor/acceptor groups, planarization/deplanarization, and modulation of the π-conjugation length. Permutation of the used building blocks leads to a set of 54 different molecules, out of which 32 are synthesized and characterized in solution as well as in example fabricated OLED devices. This setup allows for color fine-tuning in the range of 412 nm to 540 nm with typical steps of 4 nm. In addition, to further benefit from the large experimental data set the spectroscopic results are used to benchmark quantum chemical computations, which show excellent agreement thus highlighting the potential of these calculations to guide future syntheses.

[18F]Fluoroalkyl azides for rapid radiolabeling and (Re)investigation of their potential towards in vivo click chemistry.

In recent years, radiofluorinated alkyl azides have been reported for click radiolabeling and pretargeted PET imaging, but only little is known about the biodistribution and metabolism of these compounds. In this work, we present a significantly improved procedure for the synthesis of [18F]fluoroethyl azide and reinvestigated this radiolabeled probe in detail showing poor stability and very restricted suitability for in vivo application. Therefore, modified low-molecular-weight [18F]fluoroalkyl azides were developed. Propargyl-tagged endomorphin-1 (as model compound) was successfully radiolabeled in high yield and short reaction time making these probes useful and efficient bioorthogonal tools for rapid radiolabeling. Biodistribution, pharmacokinetics and in vivo stability were studied by preclinical PET/MR scanning and metabolite analysis. The results of this study revealed only limited applicability of [18F]fluoroalkyl azides for in vivo application.

Charge-transfer states in triazole linked donor-acceptor materials: strong effects of chemical modification and solvation.

A series of 1,2,3-triazole linked donor-acceptor chromophores are prepared by Click Chemistry from ene-yne starting materials. The effects of three distinct chemical variations are investigated: enhancing the acceptor strength through oxidation of the sulphur atom, alteration of the double bond configuration, and variation of the triazole substitution pattern. A detailed photophysical characterization shows that these alterations have a negligible effect on the absorption while dramatically altering the emission wavelengths. In addition, strong solvatochromism is found leading to significant red shifts in the case of polar solvents. The experimental findings are rationalized and related to the electronic structure properties of the chromophores by time-dependent density functional theory as well as the ab initio algebraic diagrammatic construction method for the polarization propagator in connection with a new formalism allowing to model the influence of solvation onto long-lived excited states and their emission energies. These calculations highlight the varying degree of intramolecular charge transfer character present for the different molecules and show that the amount of charge transfer is strongly modulated by the conducted chemical modifications, by the solvation of the chromophores, and by the structural relaxation in the excited state. It is, furthermore, shown that enhanced charge separation, as induced by chemical modification or solvation, reduces the singlet-triplet gaps and that two of the investigated molecules possess sufficiently low gaps to be considered as candidates for thermally activated delayed fluorescence.

Impact of phase I metabolism on uptake, oxidative stress and genotoxicity of the emerging mycotoxin alternariol and its monomethyl ether in esophageal cells.

Studies on the genotoxicity of Alternaria mycotoxins focus primarily on the native compounds. Alternariol (AOH) and its methyl ether (AME) have been reported to represent substrates for cytochrome P450 enzymes, generating hydroxylated metabolites. The impact of these phase I metabolites on genotoxicity remains unknown. In the present study, the synthesis and the toxicological effects of the metabolites 4-hydroxy alternariol (4-OH-AOH) and 4-hydroxy alternariol monomethyl ether (4-OH-AME) are presented and compared to the effects of the parent molecules. Although the two phase I metabolites contain a catecholic structure, which is expected to be involved in redox cycling, only 4-OH-AOH increased reactive oxygen species (ROS) in human esophageal cells (KYSE510), 4 times more pronounced than AOH. No ROS induction was observed for 4-OH-AME, although the parent compound showed some minor impact. Under cell-free conditions, both metabolites inhibited topoisomerase II activity comparable to their parent compounds. In KYSE510 cells, both metabolites were found to enhance the level of transient DNA-topoisomerase complexes in the ICE assay. Although the level of ROS was significantly increased by 4-OH-AOH, neither DNA strand breaks nor enhanced levels of formamidopyrimidine-DNA-glycosylase (FPG)-sensitive sites were observed. In contrast, AOH induced significant DNA damage in KYSE510 cells. Less pronounced or even absent effects of hydroxylated metabolites compared to the parent compounds might at least partly be explained by their poor cellular uptake. Glucuronidation as well as sulfation appear to have only a minor influence. Instead, methylation of 4-OH-AOH seems to be the preferred way of metabolism in KYSE510 cells, whereby the toxicological relevance of the methylation product remains to be clarified.

A Versatile One-Pot Access to Cyanoarenes from ortho- and para-Quinones: Paving the Way for Cyanated Functional Materials.

A generally applicable direct synthesis of cyanoarenes from quinones is presented. Particular emphasis is placed on the preparation of precursors and target molecules relevant for organic materials, including halogenated cyanoarenes and larger cyanated acenes. The reaction and work-up protocols are adjusted for the challenges presented by the different substrates and products. Screening results of the initial reaction optimization are given to further facilitate adaptation to other synthetic problems. The universality of the reaction is finally highlighted by successful substitution of para-quinones by an ortho-quinone as the starting material.

Structure-Property Relationships in Click-Derived Donor-Triazole-Acceptor Materials.

To shed light on intramolecular charge-transfer phenomena in 1,2,3-triazole-linked materials, a series of 1,2,3-triazole-linked push-pull chromophores were prepared and studied experimentally and computationally. Investigated modifications include variation of donor and/or acceptor strength and linker moiety as well as regioisomers. Photophysical characterization of intramolecular charge-transfer features revealed ambipolar behavior of the triazole linker, depending on the substitution position. Furthermore, non-centrosymmetric materials were subjected to second-harmonic generation measurements, which revealed the high nonlinear optical activity of this class of materials.

Deoxynivalenol-sulfates: identification and quantification of novel conjugated (masked) mycotoxins in wheat.

We report the identification of deoxynivalenol-3-sulfate and deoxynivalenol-15-sulfate as two novel metabolites of the trichothecene mycotoxin deoxynivalenol in wheat. Wheat ears which were either artificially infected with Fusarium graminearum or directly treated with the major Fusarium toxin deoxynivalenol (DON) were sampled 96 h after treatment. Reference standards, which have been chemically synthesized and confirmed by NMR, were used to establish a liquid chromatography-electrospray ionization (LC-ESI)-MS/MS-based "dilute and shoot" method for the detection, unambiguous identification, and quantification of both sulfate conjugates in wheat extracts. Using this approach, detection limits of 0.003 mg/kg for deoxynivalenol-3-sulfate and 0.002 mg/kg for deoxynivalenol-15-sulfate were achieved. Matrix-matched calibration was used for the quantification of DON-sulfates in the investigated samples. In DON-treated samples, DON-3-sulfate was detected in the range of 0.29-1.4 mg/kg fresh weight while DON-15-sulfate concentrations were significantly lower (range 0.015-0.061 mg/kg fresh weight). In Fusarium-infected wheat samples, DON-3-sulfate was the only detected sulfate conjugate (range 0.022-0.059 mg/kg fresh weight). These results clearly demonstrate the potential of wheat to form sulfate conjugates of DON. In order to test whether sulfation is a detoxification reaction in planta, we determined the ability of the sulfated DON derivatives to inhibit in vitro protein synthesis of wheat ribosomes. The results demonstrate that both DON-sulfates can be regarded as detoxification products. DON-15-sulfate was about 44× less inhibitory than the native toxin, and no toxicity was observed for DON-3-sulfate in the tested range.

Methylthiodeoxynivalenol (MTD): insight into the chemistry, structure and toxicity of thia-Michael adducts of trichothecenes.

Methylthiodeoxynivalenol (MTD), a novel derivative of the trichothecene mycotoxin deoxynivalenol (DON), was prepared by applying a reliable procedure for the formal Michael addition of methanethiol to the conjugated double bond of DON. Structure elucidation revealed the preferred formation of the hemiketal form of MTD by intramolecular cyclisation between C8 and C15. Computational investigations showed a negative total reaction energy for the hemiketalisation step and its decrease in comparison with theoretical model compounds. Therefore, this structural behaviour seems to be a general characteristic of thia-Michael adducts of type B trichothecenes. MTD was shown to be less inhibitory for a reticulocyte lysate based in vitro translation system than the parent compound DON, which supports the hypothesis that trichothecenes are detoxified through thia-adduct formation during xenobiotic metabolism.

Isolation and structure elucidation of pentahydroxyscirpene, a trichothecene Fusarium mycotoxin.

Pentahydroxyscirpene, a novel trichothecene-type compound, was isolated from Fusarium-inoculated rice. The structure of pentahydroxyscirpene was elucidated by 1D and 2D NMR spectroscopy and X-ray single-crystal diffraction. The conformation in solution was determined by NOESY experiments supported by quantum chemical calculations. In vitro toxicity tests showed that pentahydroxyscirpene inhibits protein synthesis as do other trichothecenes.

Sulfation of deoxynivalenol, its acetylated derivatives, and T2-toxin.

The synthesis of several sulfates of trichothecene mycotoxins is presented. Deoxynivalenol (DON) and its acetylated derivatives were synthesized from 3-acetyldeoxynivalenol (3ADON) and used as substrate for sulfation in order to reach a series of five different DON-based sulfates as well as T2-toxin-3-sulfate. These substances are suspected to be formed during phase-II metabolism in plants and humans. The sulfation was performed using a sulfuryl imidazolium salt, which was synthesized prior to use. All protected intermediates and final products were characterized via NMR and will serve as reference materials for further investigations in the fields of toxicology and bioanalytics of mycotoxins.

Crystal structures of 2,5-di-azido-1,4-phenyl-ene di-acetate and 2,5-di-azido-1,4-phenyl-ene dibutyrate.

The asymmetric units of the title compounds, C10H8N6O4, (I), and C14H16N6O4, (II), each contain half of the respective mol-ecule which is completed by inversion symmetry. The two molecules differ in the ester moiety (acetate versus butyrate) and the crystal symmetry is different, i.e. triclinic for (I) and monoclinic for (II). The di-azido-phenyl-ene moieties are essentially planar [maximum deviation of 0.0216 (7) Šfor (I) and 0.0330 (14) Šfor (II)], and the ester functionalities are almost perpendicular to these planes, making dihedral angles of 79.93 (3)° for (I) and 79.42 (6)° for (II). In the crystals of both (I) and (II), there are no significant inter-molecular inter-actions present.

Isotypic crystal structures of 2,6-di-bromo-N,N-bis-(4-nitro-phen-yl)aniline and 2,6-di-chloro-N,N-bis-(4-nitro-phen-yl)aniline.

In the mol-ecules of the two isotypic title compounds, C18H11Br2N3O4 (I) and C18H11Cl2N3O4 (II), the tri-phenyl-amine N atoms show no sign of pyramidalization, with marginal displacements of the N atoms from the mean plane of the three connecting C atoms: 0.0058 (13) Šfor the Br compound (I) and 0.0074 (9) Šfor the Cl compound (II). In the crystals, mol-ecules are linked through C-H⋯O hydrogen bonds between phenyl rings and nitro groups and by X⋯O (X = Br, Cl) inter-actions, that are shorter than the sum of the van der Waals radii, leading to a three-dimensional network.

Crystal structure of trans-1,4-bis-[(tri-methyl-sil-yl)-oxy]cyclo-hexa-2,5-diene-1,4-dicarbo-nitrile.

The asymmetric unit of the title compound, C14H22N2O2Si2, contains one half of the mol-ecule, which is completed by inversion symmetry. The cyclo-hexa-2,5-diene ring is exactly planar and reflects the bond-length distribution of a pair of located double bonds [1.3224 (14) Å] and two pairs of single bonds [1.5121 (13) and 1.5073 (14) Å]. The tetra-hedral angle between the sp (3)-C atom and the two neighbouring sp (2)-C atoms in the cyclo-hexa-2,5-diene ring is enlarged by about 3°.