Efficient copper-based DNA cleavers from carboxylate benzimidazole ligands


Four copper(II) coordination compounds from 2-benzimidazole propionic acid (Hbzpr) and 4-(benzimidazol-2-yl)-3-thiobutanoic acid (Hbztb) were synthesized and fully characterized by elemental analyses, electronic spectroscopy, FT-IR and mass spectrometry. The molecular structure for the four complexes was confirmed by single-crystal X-ray crystallography. The DNA-interacting properties of the two trinuclear and two mononuclear compounds were investigated using different spectroscopic techniques including absorption titration experiments, fluorescence spectroscopy and circular dichroism spectroscopy. Trinuclear [Cu3(bzpr)4(H2O)2](NO3)2·3H2O·CH3OH (2) and [Cu3(bzpr)4Cl2]·3H2O (3) bind to DNA through non-intercalative interactions, while for mononuclear [Cu(bzpr)2(H2O)]·2H2O (1) and [Cu(bztb)2]·2H2O (4), at minor concentrations in relation to the DNA, a groove binding interaction is favored, while at higher concentrations an intercalative mode is preferred. The nuclease properties of all complexes were studied by gel electrophoresis, which showed that they were able to cleave supercoiled plasmid DNA (form I) to the nicked form (form II). Compound 4 is even capable of generating linear form III (resulting from double-strand cleavage). The proposed mechanism of action involves an oxidative pathway (Fenton-type reaction), which produces harmful reactive species, like hydroxyl radicals.

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The financial support from CONACYT, grant CB2012-178851 and DGAPA-UNAM for grant IN224516 is acknowledged. V.A.B.-G. thanks a CONACYT scholarship. P.G. acknowledges the financial support from the Ministerio de Ciencia, Innovación y Universidades (projects CTQ2015-70371-REDT and CTQ2017-88446-R AEI/FEDER, UE). We thank P. Fierro for technical support.

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Correspondence to Patrick Gamez or Norah Barba-Behrens.

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Barrera-Guzmán, V.A., Rodríguez-Hernández, E.O., Ortíz-Pastrana, N. et al. Efficient copper-based DNA cleavers from carboxylate benzimidazole ligands. J Biol Inorg Chem 23, 1165–1183 (2018). https://doi.org/10.1007/s00775-018-1598-9

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  • Copper(II) complexes
  • 2-Carboxylate benzimidazoles
  • ct-DNA
  • pBr322 DNA
  • DNA-cleaving properties