Efficient Increase of DNA Cleavage Activity of a Diiron(III) Complex by a Conjugating Acridine Group

A new diferric complex, Fe 2 L b , in which a DNA intercalator (acridine) is linked to a precursor diferric complex (Fe 2 L a ), has been designed and synthesised as a hydrolytic cleaving agent of DNA. Compared with Fe 2 L a (without the DNA intercalator) (L a : 2,6‐bis{[(2‐hydroxybenzyl)(pyridin‐2‐yl)methylamino]methyl}‐4‐methylphenol), Fe 2 L b [L b : 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 2 L a 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 2 L a shows a rate acceleration increase of 4.7 × 10 6 times in the hydrolysis of BNPP. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)