DNA cleavage induced by [Cu(L)x(NO3)2] (L = 2,2′-dipyridylamine, 2,2′-bipyridine, dipicolylamine, x = 1 or 2): Effect of the ligand structure

Ji Hye Kwon, Hee Jin Park, Nataraj Chitrapriya, Tae Sub Cho, Soojin Kim, Jinheung Kim, In Hong Hwang, Cheal Kim, Seog K. Kim

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14 Scopus citations

Abstract

The efficiency of [Cu(2,2′-bipyridine)2(NO 3)]NO3, [Cu(2,2′-dipyridylamine)2(NO 3)2], and [Cu(dipicolylamine)2(NO 3)2] complexes (complex 1, 2 and 3, respectively) in oxidative DNA cleavage was examined by electrophoresis and linear dichroism (LD). Among the three Cu complexes, complex 1 showed the highest efficiency in super-coiled DNA (scDNA) cleavage in electrophoresis. The presence of tiron, a superoxide radical scavenger, suppressed the reaction almost completely. The LD signal at 260 nm decreased gradually as the time passed. The decrease in LD magnitude was explained best by the sum of the two single exponential curves. This suggests that the cleavage reaction involves two first order kinetic processes; an increase in flexibility due to scission of one of the strands and a shortening in the DNA stem due to cut of both strands of double stranded DNA (dsDNA). In agreement with the electrophoresis data, complex 1 exhibited the highest efficiency with the superoxide radical found to be the essential reactive oxygen species. The order of efficiency in both scDNA and dsDNA was as follows: complex 1 > complex 2 > complex 3. The electrochemical properties alone were insufficient to explain the observed efficiencies, even though reduction of the central Cu ion is essential for the oxidative DNA cleavage. This highlights the importance of an ability to ligate the molecular oxygen (or hydrogen peroxide) to the central Cu ion to produce the superoxide radical, in addition to the reduction of Cu ion, in oxidative DNA cleavage.

Original languageEnglish
Pages (from-to)79-86
Number of pages8
JournalJournal of Inorganic Biochemistry
Volume131
DOIs
StatePublished - 2014

Bibliographical note

Funding Information:
This work was supported by National Research Foundation of Korea (Grant number: 2012-008875 ).

Keywords

  • Cu complex
  • DNA
  • DNA cleavage
  • Linear dichroism
  • Oxidation

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