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Efficient copper-based DNA cleavers from carboxylate benzimidazole ligands

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Abstract

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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Acknowledgements

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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Authors and Affiliations

  1. Departamento de Química Inorgánica, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, 04510, Mexico City, Mexico

    Víctor A. Barrera-Guzmán, Edgar O. Rodríguez-Hernández & Norah Barba-Behrens

  2. Departamento de Química, Cinvestav, A. P. 14-740, 07000, Mexico City, Mexico

    Naytzé Ortíz-Pastrana

  3. Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, 04510, Mexico City, Mexico

    Ricardo Domínguez-González

  4. Departament de Química Inorgánica y Orgánica, Universitat de Barcelona, Martí I Franqués 1-11, 08028, Barcelona, Spain

    Ana B. Caballero & Patrick Gamez

  5. Institute of Nanoscience and Nanotechnology (IN2UB), Martí i Franquès 1-11, 08028, Barcelona, Spain

    Ana B. Caballero & Patrick Gamez

  6. Catalan Institution for Research and Advanced Studies, Passeig Lluís Companys 23, 08010, Barcelona, Spain

    Patrick Gamez

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  1. Víctor A. Barrera-Guzmán
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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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  • DOI: https://doi.org/10.1007/s00775-018-1598-9

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