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Indexed by:期刊论文

Date of Publication:2007-12-01

Journal:EUROPEAN JOURNAL OF INORGANIC CHEMISTRY

Included Journals:SCIE、Scopus

Issue:34

Page Number:5400-5407

ISSN No.:1434-1948

Key Words:DNA cleavage; iron complex; diiron(III) complex; intercalator; acridine

Abstract:A new diferric complex, Fe2Lb, in which a DNA intercalator (acridine) is linked to a precursor diferric complex (Fe2La), has been designed and synthesised as a hydrolytic cleaving agent of DNA. Compared with Fe2La (without the DNA intercalator) (L-a: 2,6-bis{[(2-hydroxybenzyl)(pyridin-2-yl)methylamino]methyl)-4-methylphenol), Fe2Lb [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 Fe2La 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 Fe2La shows a rate acceleration increase of 4.7 x 10(6) times in the hydrolysis of BNPP. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)