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  - Release of Singlet Oxygen from Organic Peroxides under Mild Conditions
JF  - ChemPhotoChem
N2  - Singlet oxygen can be released in the dark in nearly quantitative yield from endoperoxides of naphthalenes, anthracenes and pyridones as an alternative to its generation by photosensitization. Recently, new donor systems have been designed which operate at very low temperatures but which are prepared from their parent forms at acceptable rates. Enhancement of the reactivity of donors is conveniently achieved by the design of the substitution pattern or through the use of plasmonic heating of nanoparticle-bound donors. The most important aim of these donor molecules is to transfer singlet oxygen in a controlled and directed manner to a target. Low temperatures and the linking between donors and acceptors reduce the random walk of oxygen and may force an attack at the desired position. By using chiral donor systems, new stereocenters might be introduced into prochiral acceptors.
KW  - donor-acceptor systems
KW  - oxygenation
KW  - peroxides
KW  - polycycles
KW  - retro reactions
Y1  - 2018
U6  - https://doi.org/10.1002/cptc.201700235
SN  - 2367-0932
VL  - 2
IS  - 7
SP  - 548
EP  - 558
PB  - Wiley-VCH
CY  - Weinheim
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  -