Skip to main content

Efficient copper-based DNA cleavers from carboxylate benzimidazole ligands

JBIC Journal of Biological Inorganic Chemistry volume 23, pages 1165–1183 (2018)Cite this article

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.

Graphical abstract

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Scheme 1
Fig. 1: a
Fig. 2
Fig. 3: a
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8: a
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16
Fig. 17
Fig. 18
Fig. 19

References

  1. Tullius TD (1989) Metal-DNA chemistry. ACS Symposium Series, vol 402. American Chemical Society, Washington DC

    Book  Google Scholar 

  2. Loehrer PJ, Einhorn LH (1984) Ann Intern Med 100:704–713

    Article  CAS  Google Scholar 

  3. Lippert B (1999) Cisplatin: chemistry and biochemistry of a leading anticancer drug. VHCA & Wiley-VCH, Zurich

    Book  Google Scholar 

  4. Cuello-Garibo JA, James CC, Siegler MA, Bonnet S (2017) Chem Sq 1:2

    Article  Google Scholar 

  5. Stern BR (2010) J Toxicol Environ Health Part A 73:114–127

    Article  CAS  Google Scholar 

  6. Lippard SJ, Berg JM (1994) Principles of bioinorganic chemistry. Mill Valley, California

    Google Scholar 

  7. Jagadeesh M, Kalangi SK, Krishna LS, Reddy AV (2014) Spectrochim Acta, Part A 118:552–556

    Article  CAS  Google Scholar 

  8. Sayen S, Carlier A, Tarpin M, Guillon E (2013) J Inorg Biochem 120:39–43

    Article  CAS  Google Scholar 

  9. Duff B, Thangella VR, Creaven BS, Walsh M, Egan DA (2012) Eur J Pharmacol 689:45–55

    Article  CAS  Google Scholar 

  10. Ali I, Wani WA, Saleem K, Hseih M-F (2013) Polyhedron 56:134–143

    Article  CAS  Google Scholar 

  11. Li G-Y, Du K-J, Wang J-Q, Liang J-W, Kou J-F, Hou X-J, Ji L-N, Chao H (2013) J Inorg Biochem 119:43–53

    Article  CAS  Google Scholar 

  12. Silveira VC, Benezra H, Luz JS, Georg RC, Oliveira CC, Ferreira AMC (2011) J Inorg Biochem 105:1692–1703

    Article  Google Scholar 

  13. Patel MN, Dosi PA, Bhatt BS, Thakkar VR (2011) Spectrochim Acta Part A 78:763–770

    Article  Google Scholar 

  14. Kellett A, Howe O, Connor MO, McCann M, Creaven BS, McClean S, Kia AF-A, Casey A, Devereux M (2012) Free Radical Biol Med 53:564–576

    Article  CAS  Google Scholar 

  15. Kashanian S, Khodaei MM, Roshanfekr H, Shahabadi N, Mansouri G (2012) Spectrochim Acta Part A 86:351–359

    Article  CAS  Google Scholar 

  16. Grau J, Renau C, Caballero AB, Caubet A, Pockaj M, Lorenzo J, Gamez P (2018) Dalton Trans 47:4902–4908

    Article  CAS  Google Scholar 

  17. Schreiber JP, Deune M (1969) Biopolymers 8:139–152

    Article  CAS  Google Scholar 

  18. Chikira M, Inue M, Negane R, Harada W, Shindo H, Antholine WE (2000) J Inorg Biochem 78:243–249

    Article  Google Scholar 

  19. Morrow JR, Iranzo O (2004) Curr Opin Chem Biol 8:192–200

    Article  CAS  Google Scholar 

  20. Erxleben A Interactions of copper complexes with nucleic acids

  21. Spingler B, Da Pieve C (2005) Dalton Trans 1637–1643

  22. Medina-Molner A, Rohner M, Pandiarajan D, Spingler B (2015) Dalton Trans 44:3664–3672

    Article  CAS  Google Scholar 

  23. Harada W, Nojima T, Shibayama A, Ueda H, Sindo H, Chikira M (1996) J Inorg Biochem 64:273–285

    Article  CAS  Google Scholar 

  24. Negane R, Chikira M, Oumi M, Shindo H, Antholine WE (2000) J Inorg Biochem 78:243–249

    Article  Google Scholar 

  25. Li D-D, Tian J-L, Gu W, Liu X, Zeng H-H, Yan S-P (2011) J Inorg Biochem 105:894–901

    Article  CAS  Google Scholar 

  26. Suntharalingam K, White AJP, Vilar R (2010) Inorg Chem 49:8371–8380

    Article  CAS  Google Scholar 

  27. Suntharalingam K, Hunt DJ, Duarte AA, White AJP, Mann DJ, Vilar R (2012) Chem Eur J 41:4955–4965

    Google Scholar 

  28. Skinnerm WA, Schelstraete MGM, Baker BR (1959) J Org Chem 24:1827

    Article  Google Scholar 

  29. Biron KK (2006) Antivir Res 71:154–163

    Article  CAS  Google Scholar 

  30. Middleton T, Lim HB, Montgomery D, Rockway T, Tang H, Cheng X, Lu L, Mo H, Kohlbrenner WE, Molla A, Kati WM (2004) Antivir Res 64:35–45

    Article  CAS  Google Scholar 

  31. Labanauskas L, Brukštus A, Udre˙ naite˙ E, Gaidelis P, Bucˇinskaite˙ V (2003) Chemija (Vilnius) 14:49

    CAS  Google Scholar 

  32. Sari H, Covington AK (2005) J Chem Eng Data 50:1425–1429

    Article  CAS  Google Scholar 

  33. Meaney M, Allister J, McKinstry B, McLaughlin K, Brennan GP, Forbes AB, Fairweather I (2007) Parasitol Res 100:1091–1104

    Article  CAS  Google Scholar 

  34. Mirskova AN, Levkovskaya GG, Mirskov RG, Voronkov MG (2008) Russ J Org Chem 44:1478–1485

    Article  CAS  Google Scholar 

  35. Luneau D, Rey P (2005) Coord Chem Rev 249:2591–2611

    Article  CAS  Google Scholar 

  36. Kabatc J, Jurek K (2012) Polymer 53:1973–1980

    Article  CAS  Google Scholar 

  37. Yoe F, Flores-Álamo M, Morales F, Escudero R, Cortés-Hernández H, Castro M, Barba-Behrens N (2014) Inorg Chim Acta 423:36–45

    Article  CAS  Google Scholar 

  38. Sheldrick GM (2015) Acta Cryst. A71:3–8

    Google Scholar 

  39. Hübschle CB, Sheldrick GM, Dittrich B (2011) J Appl Crystallogr 44:1281–1284

    Article  Google Scholar 

  40. Spek AL (2015) Acta Cryst. C71:9–18

    Google Scholar 

  41. Reichmann MF, Rice SA, Thomas CA, Doty P (1954) J Am Chem Soc 76:3047–3053

    Article  CAS  Google Scholar 

  42. Wolfe A, Shimer GHJ, Meehan T (1987) Biochemistry 26:6392–6396

    Article  CAS  Google Scholar 

  43. Lakowicz JR, Weber G (1973) Biochemistry 12(21):4161–4170

    Article  CAS  Google Scholar 

  44. Shubsda MF, Goodisman J, Dabrowiak JC (1997) J Biochem Biophys Methods 34:73–79

    Article  CAS  Google Scholar 

  45. Patel MN, Dosi PA, Bhatt BS (2010) Polyhedron 29:3238–3245

    Article  CAS  Google Scholar 

  46. Lever ABP (1968) J Chem Ed 45:711–712

    Article  CAS  Google Scholar 

  47. Valderrama-Negrón AC, Alves WA, Cruz ÁS, Rogero SO, de Oliveira Silva D (2011) Inorg Chim Acta 367:58–92

    Article  Google Scholar 

  48. Nakamoto K (1986) Infrared and Raman Spectra of Inorganic and Coordination Compounds. Wiley-Interscience

  49. Addison AW, Rao TN, Reedijk J, van Rijn J, Verschoor GCJ (1984) Chem Soc 7:1349–1356

    Google Scholar 

  50. Klein A, Neugebauer E, Krest A, Lüning A, Garbe S, Arefyeva N, Schlörer N (2015) Inorganics 3:118–138

    Article  CAS  Google Scholar 

  51. Jahn HA, Teller E (1937) Proc R Soc Lond Ser A161:220–235

    Article  Google Scholar 

  52. Matthews CJ, Heath SL, Elsegood MRJ, Clegg W, Leese TA, Lockhart JC (1998) J Chem Soc Dalton Trans 12:1973–1977

    Article  Google Scholar 

  53. Kelly JM, Tossi AB, McConnell DJ, OhUigin C (1985) Nucleic Acids Res 13:6017–6034

    Article  CAS  Google Scholar 

  54. Meenongwa A, Chaveerach U, Siriwong K (2011) Inorg Chim Acta 366:357–365

    Article  CAS  Google Scholar 

  55. Chaveerach U, Meenongwa A, Trongpanich Y, Soikum C, Chaveerach P (2010) Polyhedron 29:731–738

    Article  CAS  Google Scholar 

  56. Marmur J (1961) J Mol Biol 3:208–218

    Article  CAS  Google Scholar 

  57. Meenongwa A, Brissos RF, Soikum C, Chaveerach P, Gamez P, Trongpanich Y, Chaveerach U (2015) N J Chem 39:664–675

    Article  CAS  Google Scholar 

  58. Nyarko E, Hanada N, Habib A, Tabata M (2004) Inorg Chim Acta 357:739–745

    Article  CAS  Google Scholar 

  59. Silveira VC, Benezra H, Luz JS, Georg RC, Oliveira CC, Ferreira AMC (2011) J Inorg Biochem 105:1692–1703

    Article  Google Scholar 

  60. Ling X, Zhong W, Huang Q, Ni K (2008) J Photochem Photobiol B 93:172–176

    Article  CAS  Google Scholar 

  61. Ivanov VI, Minchenkova LE, Schyolkina AK, Poletayev AI (1973) Biopolymers 12:89–110

    Article  CAS  Google Scholar 

  62. Collins CH, Lyne PM (1970) Microbiological methods. University Park Press, Baltimore

    Google Scholar 

  63. Sigman DS, Chen C-HB (1986) Acc Chem Res 19:180–186

    Article  CAS  Google Scholar 

Download references

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.

Author information

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

Authors
  1. Víctor A. Barrera-Guzmán
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Edgar O. Rodríguez-Hernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naytzé Ortíz-Pastrana
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ricardo Domínguez-González
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ana B. Caballero
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Patrick Gamez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Norah Barba-Behrens
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Patrick Gamez or Norah Barba-Behrens.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 262 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-018-1598-9

Keywords

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