@article{GeroldingerTonnerFudickaretal.2018,
  author    = {Geroldinger, Gerald and Tonner, Matthias and Fudickar, Werner and De Sarkar, Sritama and Dighal, Aishwarya and Monzote, Lianet and Staniek, Katrin and Linker, Torsten and Chatterjee, Mitali and Gille, Lars},
  title     = {Activation of anthracene endoperoxides in leishmania and impairment of mitochondrial functions},
  series = {Molecules},
  volume    = {23},
  journal   = {Molecules},
  number    = {7},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {1420-3049},
  doi       = {10.3390/molecules23071680},
  pages     = {22},
  year      = {2018},
  abstract  = {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.},
  language  = {en}
}
@article{FudickarLinker2019,
  author    = {Fudickar, Werner and Linker, Torsten},
  title     = {Theoretical insights into the effect of solvents on the [4+2] cycloaddition of singlet oxygen to substituted anthracenes},
  series = {Journal of physical organic chemistry},
  volume    = {32},
  journal   = {Journal of physical organic chemistry},
  number    = {7},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {0894-3230},
  doi       = {10.1002/poc.3951},
  pages     = {9},
  year      = {2019},
  abstract  = {The [4 + 2] cycloadditions of singlet oxygen to 9,10-diphenylanthracene (1) and the meta and para isomers of 9,10-dipyridylanthracene (2m/p) and 9,10-methoxyphenylanthracene (3m/p) have been studied by density functional calculations in the gas phase at the UB3LYP/6-31G* level and for the first time in solvents at the conductor-like polarizable continuum model (CPCM) UM062X/6-31G* level. The differences in calculated transition state (TS) energies derived from this method are in line with experimentally observed reactivity orders in solution. For the gas-phase reaction, the first TS of the stepwise pathway (TS1) has biradical character, and its energy lies below the energy of the TS of the concerted path (TSconc). In contrast, in the solvent acetonitrile, TS1 resembles a zwitterion and lies significantly higher than the TSconc. Thus, a concerted mechanism applies in solvents, and the energy gap between the TS of the two processes decreases with decreasing polarity. A change from a pyridyl against a methoxyphenyl substituent in the para position causes a maximal reduction of the activation barrier by approximately 1.7 kcal/mol, resulting in a fivefold increased reactivity.},
  language  = {en}
}