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Preferential DNA photocleavage potency of Zn(II) over Ni(II) derivatives of carboxymethyl tetracationic porphyrin: the role of the mode of binding to DNA

  • Kovaleva, Oxana A.1, 2
  • Tsvetkov, Vladimir B.3, 4
  • Mamaeva, Olga K.1
  • Ol’shevskaya, Valentina A.5
  • Makarenkov, Anton V.5
  • Dezhenkova, Lyubov G.6
  • Semeikin, Alexander S.7
  • Borisova, Olga F.1
  • Shtil, Alexander A.8, 9
  • Shchyolkina, Anna K.1
  • Kaluzhny, Dmitry N.1
  • 1 Russian Academy of Sciences, Engelhardt Institute of Molecular Biology, Moscow, 119991, Russia , Moscow (Russia)
  • 2 Moscow Institute of Physics and Technology (State University), Dolgoprudny, 141700, Russia , Dolgoprudny (Russia)
  • 3 Institute for Physical Chemical Medicine, Moscow, 117312, Russia , Moscow (Russia)
  • 4 Russian Academy of Sciences, Topchiev Institute of Petrochemical Synthesis, Moscow, 119991, Russia , Moscow (Russia)
  • 5 Russian Academy of Sciences, Nesmeyanov Institute of Organoelement Compounds, Moscow, 119991, Russia , Moscow (Russia)
  • 6 Gause Institute of New Antibiotics, Moscow, 119021, Russia , Moscow (Russia)
  • 7 Ivanovo State University of Chemistry and Technology, Ivanovo, 153000, Russia , Ivanovo (Russia)
  • 8 Blokhin Cancer Center, Moscow, 115478, Russia , Moscow (Russia)
  • 9 Moscow Engineering and Physics Institute, Moscow, 115409, Russia , Moscow (Russia)
Published Article
European Biophysics Journal
Publication Date
Aug 28, 2014
DOI: 10.1007/s00249-014-0984-7
Springer Nature


The porphyrin-based photosensitizers capable of binding to DNA are perspective drug candidates. Here we report the interactions with calf thymus DNA of 5,10,15,20-tetrakis(N-carboxymethyl-4-pyridinium)porphyrin (P1) and its derivatives containing Zn(II) or Ni(II) in the coordination sphere. These interactions were studied with absorption and circular dichroism spectroscopy. NiP1 and ZnP1 formed different types of complexes with DNA. NiP1 intercalated into the double helix, whereas ZnP1 bound the DNA groove. Compound P1 displayed both binding modes. The ZnP1-DNA binding constant was approximately three times smaller than the respective values for P1-DNA and NiP1-DNA complexes. Light induced degradation of the reactive oxygen species (ROS) trap 1,3-diphenylisobenzofuran in the presence of P1 and its metal derivatives revealed that NiP1 was a weaker photooxidative agent, whereas P1 and ZnP1 generated ROS to similar extents. Nevertheless, the DNA photodamaging effect of ZnP1 was the most pronounced. Illumination of the supercoiled plasmid caused single-strand DNA photocleavage in the presence of P1 and ZnP1; double strand breaks were detectable with micromolar concentrations of ZnP1. The concentration of ZnP1 required for plasmid photonicking was two times smaller than that of P1 and ~20 times lower than that for NiP1. Thus, the modes of P1, NiP1 and ZnP1 binding to DNA determine the differential photodamaging potency of these porphyrins. A greater accessibility to the solvent of the groove binder ZnP1, compared to the shielded intercalator NiP1 and the intercalated P1 molecules, allows for an efficient local generation of ROS followed by DNA photocleavage.

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