TY - JOUR A1 - Zehm, Daniel A1 - Fudickar, Werner A1 - Hans, Melanie A1 - Schilde, Uwe A1 - Kelling, Alexandra A1 - Linker, Torsten T1 - 9,10-Diarylanthracenes as molecular switches : syntheses, properties, isomerisations and their reactions with singlet oxygen N2 - A series of 9,10-diarylanthracenes with various substituents at the ortho positions have been synthesised by palladium-catalysed cross-coupling reactions. Such compounds exhibit interesting physical properties and can be applied as molecular switches. Despite the high steric demand of the substituents, products were formed in moderate-to-good yields. In some cases, microwave conditions further improved yields. Bis-coupling afforded two isomers (syn and anti) that do not interconvert at room temperature. These products were easily separated and their relative stereochemistries were unequivocally assigned by NMR spectroscopy and X-ray analysis. The syn and anti isomers exhibit different physical properties (e.g., melting points and solubilities) and interconversion by rotation around the aryl-aryl axis commences at <100 °C for fluoro-substituted diarylanthracenes and at >300 °C for alkyl- or alkoxy-substituted diarylanthracenes. The reactions with singlet oxygen were studied separately and revealed different reactivities and reaction pathways. The yields and reactivities depend on the size and electronic nature of the substituents. The anti isomers form the same 9,10-endoperoxides as the syn species, occasionally accompanied by unexpected 1,4-endoperoxides as byproducts. Thermolysis of the endoperoxides exclusively yielded the syn isomers. The interesting rotation around the aryl-aryl axis allows the application of 9,10-diarylanthracenes as molecular switches, which are triggered by light and air under mild conditions. Finally, the oxygenation and thermolysis sequence provides a simple, synthetic access to a single stereoisomer (syn) from an unselective coupling step. Y1 - 2008 SN - 0947-6539 ER - TY - JOUR A1 - Linker, Torsten A1 - Fudickar, Werner A1 - Kelling, Alexandra A1 - Schilde, Uwe T1 - Crystal structure of dimethyl 1,4-dioxaspiro[4,5]dec-6-ene-(8R)-[(3,5-dinitrobenzoyl)oxa]-(2R,3R)-dica rboxylate, C19H18N2O12 JF - Zeitschrift für Kristallographie : international journal for structural, physical and chemical aspects of crystalline materials ; New crystal structures N2 - C19H18N2O12, orthorhombic, P2(1)2(1)2(1) (no. 19), a = 6.2472(6) angstrom, b = 17.576(2) angstrom, c = 18.848(3) angstrom, V = 2069.6 angstrom(3), Z = 4, R-gt(F) = 0.0393, wR(ref)(F-2) = 0.0694, T = 210 K. Y1 - 2013 U6 - https://doi.org/10.1524/ncrs.2013.0123 SN - 1433-7266 VL - 228 IS - 2 SP - 241 EP - 242 PB - De Gruyter Oldenbourg CY - München ER - TY - JOUR A1 - Haubitz, Toni A1 - Fudickar, Werner A1 - Linker, Torsten A1 - Kumke, Michael Uwe T1 - pH-sensitive fluorescence switching of pyridylanthracenes BT - the effect of the isomeric pattern JF - The journal of physical chemistry : A, Molecules, spectroscopy, kinetics, environment & general theory N2 - 9,10-substituted anthracenes are known for their useful optical properties like fluorescence, which makes them frequently used probes in sensing applications. In this article, we investigate the fundamental photophysical properties of three pyridyl-substituted variants. The nitrogen atoms in the pyridinium six-membered rings are located in the ortho-, meta-, and para-positions in relation to the anthracene core. Absorption, fluorescence, and transient absorption measurements were carried out and were complemented by theoretical calculations. We monitored the photophysics of the anthracene derivatives in chloroform and water investigating the protonated as well as their nonprotonated forms. We found that the optical properties of the nonprotonated forms are strongly determined by the anthracene chromophore, with only small differences to other 9,10-substituted anthracenes, for example diphenyl anthracene. In contrast, protonation leads to a strong decrease in fluorescence intensity and lifetime. Transient absorption measurements and theoretical calculations revealed the formation of a charge-transfer state in the protonated chromophores, where electron density is shifted from the anthracene moiety toward the protonated pyridyl substituents. While the para- and ortho-derivatives' charge transfer is still moderately fluorescent, the meta-derivative is affected much stronger and shows nearly no fluorescence. This nitrogen-atom-position-dependent sensitivity to hydronium activity makes a combination of these fluorophores very attractive for pH-sensing applications covering a broadened pH range. KW - Absorption KW - Aromatic compounds KW - Fluorescence KW - Hydrocarbons KW - Reaction mechanisms Y1 - 2020 U6 - https://doi.org/10.1021/acs.jpca.0c09911 SN - 1089-5639 SN - 1520-5215 VL - 124 IS - 52 SP - 11017 EP - 11024 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Geroldinger, Gerald A1 - Tonner, Matthias A1 - Fudickar, Werner A1 - De Sarkar, Sritama A1 - Dighal, Aishwarya A1 - Monzote, Lianet A1 - Staniek, Katrin A1 - Linker, Torsten A1 - Chatterjee, Mitali A1 - Gille, Lars T1 - Activation of anthracene endoperoxides in leishmania and impairment of mitochondrial functions JF - Molecules N2 - Leishmaniasis is a vector-borne disease caused by protozoal Leishmania. Because of resistance development against current drugs, new antileishmanial compounds are urgently needed. Endoperoxides (EPs) are successfully used in malaria therapy, and experimental evidence of their potential against leishmaniasis exists. Anthracene endoperoxides (AcEPs) have so far been only technically used and not explored for their leishmanicidal potential. This study verified the in vitro efficiency and mechanism of AcEPs against both Leishmania promastigotes and axenic amastigotes (L. tarentolae and L. donovani) as well as their toxicity in J774 macrophages. Additionally, the kinetics and radical products of AcEPs’ reaction with iron, the formation of radicals by AcEPs in Leishmania, as well as the resulting impairment of parasite mitochondrial functions were studied. Using electron paramagnetic resonance combined with spin trapping, photometry, and fluorescence-based oximetry, AcEPs were demonstrated to (i) show antileishmanial activity in vitro at IC50 values in a low micromolar range, (ii) exhibit host cell toxicity in J774 macrophages, (iii) react rapidly with iron (II) resulting in the formation of oxygen- and carbon-centered radicals, (iv) produce carbon-centered radicals which could secondarily trigger superoxide radical formation in Leishmania, and (v) impair mitochondrial functions in Leishmania during parasite killing. Overall, the data of different AcEPs demonstrate that their structures besides the peroxo bridge strongly influence their activity and mechanism of their antileishmanial action. KW - Leishmania KW - endoperoxides KW - EPR spectroscopy KW - mitochondria KW - radicals Y1 - 2018 U6 - https://doi.org/10.3390/molecules23071680 SN - 1420-3049 VL - 23 IS - 7 PB - MDPI CY - Basel ER - TY - JOUR A1 - Fudickar, Werner A1 - Vomdran, Katja A1 - Linker, Torsten T1 - Auxiliary controlled singlet-oxygen ene reactions of cyclohexenes JF - Tetrahedron N2 - The photooxygenation of homochiral cyclohexene ketals, which are easily available from 2-cyclohexenone and L-tartrates, affords hydroperoxides and after reduction the corresponding allylic alcohols in good yields and high regioselectivities. This can be rationalized by electronic repulsions in a perepoxide intermediate and provides evidence for unfavorable 1,3 diaxial interactions with a dioxolane oxygen atom. Only low stereoselectivities were observed, due to the flexibility of the cyclohexene ring. However, the diastereomers could be separated and after cleavage of the auxiliary, 4-hydroxy-2-cyclohexen-1-one was isolated in enantiomerically pure form, which can serve as a building block for natural product synthesis. KW - singlet oxygen KW - auxiliary control KW - regioselectivity KW - stereoselectivity Y1 - 2006 U6 - https://doi.org/10.1016/j.tet.2006.07.104 SN - 0040-4020 VL - 62 IS - 46 SP - 10639 EP - 10646 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Fudickar, Werner A1 - Roder, Phillip A1 - Listek, Martin A1 - Hanack, Katja A1 - Linker, Torsten T1 - Pyridinium alkynylanthracenes as sensitizers for photodynamic therapy JF - Photochemistry and photobiology N2 - Photodynamic therapy (PDT) is a mild but effective method to treat certain types of cancer upon irradiation with visible light. Here, three isomeric methylpyridinium alkynylanthracenes 1op were evaluated as sensitizers for PDT. Upon irradiation with blue or green light, all three compounds show the ability to initiate strand breaks of plasmid DNA. The mayor species responsible for cleavage is singlet oxygen (O-1(2)) as confirmed by scavenging reagents. Only isomers 1m and 1p can be incorporated into HeLa cells, whereas isomer 1o cannot permeate through the membrane. While isomer 1m targets the cell nucleus, isomer 1p assembles in the cellular cytoplasm and impacts the cellular integrity. This is in accordance with a moderate toxicity of 1p in the dark, whereas 1m exhibits no dark toxicity. Both isomers are suitable as PDT reagents, with a CC50 of 3 mu m and 75 nm, for 1p and 1m, respectively. Thus, derivative 1m, which can be easily synthesized, becomes an interesting candidate for cancer therapy. Y1 - 2021 U6 - https://doi.org/10.1111/php.13554 SN - 0031-8655 SN - 1751-1097 VL - 98 IS - 1 SP - 193 EP - 201 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Fudickar, Werner A1 - Pavashe, Prashant A1 - Linker, Torsten T1 - Thiocarbohydrates on Gold Nanoparticles: Strong Influence of Stereocenters on Binding Affinity and Interparticle Forces JF - Chemistry - a European journal N2 - Carbohydrates carrying thiol groups at the C-2 position have been attached to gold nanoparticles (AuNPs) with stereocenters in close proximity to the surface for the first time. Their configurations can be clearly distinguished by the tendency of particle aggregation. AuNP surface plasmon resonance (SPR), X-ray photoelectron spectroscopy (XPS), and IR spectroscopy indicate that the thiocarbohydrates replace citrate molecules at different rates, causing aggregation and eventually precipitation. A quantitative formulation of this aggregation process shows that reactivities can vary by several magnitudes. Adsorption isotherms and kinetics also demonstrate that the number of thiocarbohydrates varies by a factor of two. Molecular mechanics force field (MMFF) calculations reveal their relative orientations. Based on these models, the different binding behavior can be ascribed to attractive van der Waals forces and hydrogen bonds. Such interactions occur either between the carbohydrate and AuNPs, by lateral intermolecular forces at the surface, or by interparticle attraction, in analogy to cell-surface carbohydrates of biological recognition systems. Aggregation of NPs therefore act as an indicator to differentiate between various carbohydrates with defined configurations. KW - carbohydrate recognition KW - citrate displacement KW - gold nanoparticles KW - plasmon spectroscopy KW - thiols Y1 - 2017 U6 - https://doi.org/10.1002/chem.201700846 SN - 0947-6539 SN - 1521-3765 VL - 23 SP - 8685 EP - 8693 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Fudickar, Werner A1 - Metz, Melanie A1 - Mai-Linde, Yasemin A1 - Krüger, Tobias A1 - Kelling, Alexandra A1 - Sperlich, Eric A1 - Linker, Torsten T1 - Influence of functional groups on the ene reaction of singlet oxygen with 1,4-cyclohexadienes JF - Photochemistry and photobiology : the official journal of the American Society for Photobiology N2 - The photooxygenation of 1,4-cyclohexadienes has been studied with a special focus on regio- and stereoselectivities. In all examples, only the methyl-substituted double bond undergoes an ene reaction with singlet oxygen, to afford hydroperoxides in moderate to good yields. We explain the high regioselectivities by a "large-group effect" of the adjacent quaternary stereocenter. Nitriles decrease the reactivity of singlet oxygen, presumably by quenching, but can stabilize proposed per-epoxide intermediates by polar interactions resulting in different stereoselectivities. Spiro lactams and lactones show an interesting effect on regio- and stereoselectivities of the ene reactions. Thus, singlet oxygen attacks the double bond preferentially anti to the carbonyl group, affording only one regioisomeric hydroperoxide. If the reaction occurs from the opposite face, the other regioisomer is exclusively formed by severe electrostatic repulsion in a perepoxide intermediate. We explain this unusual behavior by the fixed geometry of spiro compounds and call it a "spiro effect" in singlet oxygen ene reactions. Y1 - 2021 U6 - https://doi.org/10.1111/php.13422 SN - 0031-8655 SN - 1751-1097 VL - 97 IS - 6 SP - 1289 EP - 1297 PB - Wiley CY - Malden, Mass. ER - TY - JOUR A1 - Fudickar, Werner A1 - Linker, Torsten T1 - Release of Singlet Oxygen from Aromatic Endoperoxides by Chemical Triggers JF - Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition N2 - The generation of reactive singlet oxygen under mild conditions is of current interest in chemistry, biology, and medicine. We were able to release oxygen from dipyridylanthracene endoperoxides (EPOs) by using a simple chemical trigger at low temperature. Protonation and methylation of such EPOs strongly accelerated these reactions. Furthermore, the methyl pyridinium derivatives are water soluble and therefore serve as oxygen carriers in aqueous media. Methylation of the EPO of the ortho isomer affords the parent form directly without increasing the temperature under very mild conditions. This exceptional behavior is ascribed to the close contact between the nitrogen atom and the peroxo group. Singlet oxygen is released upon this reaction, and can be used to oxygenate an acceptor such as tetramethylethylene in the dark with no heating. Thus, a new chemical source of singlet oxygen has been found, which is triggered by a simple stimulus. KW - anthracenes KW - donor-acceptor systems KW - mild reaction conditions KW - selective oxidations KW - singlet oxygen Y1 - 2018 U6 - https://doi.org/10.1002/anie.201806881 SN - 1433-7851 SN - 1521-3773 VL - 57 IS - 39 SP - 12971 EP - 12975 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Fudickar, Werner A1 - Linker, Torsten T1 - Synthesis of Pyridylanthracenes and Their Reversible Reaction with Singlet Oxygen to Endoperoxides JF - The journal of organic chemistry N2 - The ortho, meta, and para isomers of 9,10-dipyridylanthracene 1 have been synthesized and converted into their endoperoxides 1-O-2 upon oxidation with singlet oxygen. The kinetics of this reaction can be controlled by the substitution pattern and the solvent: in highly polar solvents, the meta isomer is the most reactive, whereas the ortho isomer is oxidized fastest in nonpolar solvents. Heating of the endoperoxides affords the parent anthracenes by release of singlet oxygen. Y1 - 2017 U6 - https://doi.org/10.1021/acs.joc.7b01765 SN - 0022-3263 VL - 82 SP - 9258 EP - 9262 PB - American Chemical Society CY - Washington ER -