Efficient increase of DNA cleavage activity of a diiron(III) complex by a conjugating acridine group

Xiao Qiang Chen, Xiao Jun Peng, Jing Yun Wang, Yan Wang, Song Wu, Li Zhu Zhang, Tong Wu, Yun Kou Wu

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43 Scopus citations

Abstract

A new diferric complex, Fe2Lb, in which a DNA intercalator (acridine) is linked to a precursor diferric complex (Fe 2La), has been designed and synthesised as a hydrolytic cleaving agent of DNA. Compared with Fe2La (without the DNA intercalator) (La: 2,6-bis{[(2-hydroxybenzyl)(pyridin-2-yl) methylamino]methyl}-4-methylphenol), Fe2Lb [Lb: 5-(acridin-9-yl)-N-(3,5-bis{[(2-hydroxybenzyl)(pyridin-2-yl)methylamino]- methyl}-4-hydroxybenzyl)pentanamide] leads to a 14-fold increase in the cleavage efficiency of plasmid DNA due to the binding interaction between DNA and the acridine moiety. The interaction has been demonstrated by UV/Vis absorption, CD spectroscopy, viscidity experiments and thermal denaturation studies. The hydrolytic mechanism is supported by evidence from T4 DNA ligase assay, reactive oxygen species (ROS) quenching and BNPP [bis(4-nitrophenyl) phosphate, a DNA model] cleavage experiments. The pH dependence of the BNPP cleavage by Fe 2La in aqueous buffer media shows a bell-shaped pH-k obs profile with an optimum point around a pH of 7.0 which is in good agreement with the maximum point of the pH-dependent relative concentration curve of active species from the pH titration experiments. The determination of the initial rates at a pH of 7.36 as a function of substrate concentration reveals saturation kinetics with Michaelis-Menten-like behaviour and Fe 2La shows a rate acceleration increase of 4.7 × 106 times in the hydrolysis of BNPP.

Original languageEnglish (US)
Pages (from-to)5400-5407
Number of pages8
JournalEuropean Journal of Inorganic Chemistry
Issue number34
DOIs
StatePublished - Dec 18 2007

Keywords

  • Acridine
  • DNA cleavage
  • Diiron(III) complex
  • Intercalator
  • Iron complex

ASJC Scopus subject areas

  • Inorganic Chemistry

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    Chen, X. Q., Peng, X. J., Wang, J. Y., Wang, Y., Wu, S., Zhang, L. Z., Wu, T., & Wu, Y. K. (2007). Efficient increase of DNA cleavage activity of a diiron(III) complex by a conjugating acridine group. European Journal of Inorganic Chemistry, (34), 5400-5407. https://doi.org/10.1002/ejic.200700383