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2-(3,5-Dibromo-4-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthrolinoruthenium(II) complexes: synthesis, characterization, cytotoxicity, apoptosis, DNA-binding and antioxidant activity

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Abstract

A new ligand DBHIP and its two ruthenium(II) complexes [Ru(dmb)2(DBHIP)](ClO4)2 (1) and [Ru(dmp)2(DBHIP)](ClO4)2 (2) have been synthesized and characterized. The cytotoxicity of DBHIP and complexes 1 and 2 has been assessed by MTT assay. The apoptosis studies were carried out with acridine orange/ethidium bromide (AO/EB) staining methods. The binding behaviors of these complexes to calf thymus DNA (CT-DNA) were studied by absorption titration, viscosity measurements, thermal denaturation and photoactivated cleavage. The DNA-binding constants of complexes 1 and 2 were determined to be 8.64 ± 0.16 × 104 (s = 1.34) and 2.79 ± 0.21 × 104 (s = 2.17) M−1. The results suggest that these complexes interact with DNA through intercalative mode. The studies on the mechanism of photocleavage demonstrate that superoxide anion radical (O2 •–) and singlet oxygen (1O2) may play an important role in the DNA cleavage. The experiments on antioxidant activity show that these compounds also exhibit good antioxidant activity against hydroxyl radical (OH).

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Abbreviations

DBHIP:

2-(3,5-Dibromo-4-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline

dmb:

4,4′-Dimethyl-2,2′-bipyridine

dmp:

2,9-Dimethyl-1,10-phenanthroline

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

AO/EB:

Acridine orange/ethidium bromide

DMSO:

Dimethyl sulfoxide

RPMI:

Roswell Park Memorial Institute

DMF:

N,N-Dimethylformamide

CT-DNA:

Calf thymus DNA

MLCT:

Metal to ligand charge transfer

Tris:

Tris(hydroxymethyl)aminomethane

ES–MS:

Electrospray mass spectroscopy

NAMI-A:

[ImH][trans-RuCl4(DMSO)(Im)]

KP1019:

[IndH][trans-RuCl4(Ind)2]

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Acknowledgements

This work is supported by the National Nature Science Foundation of China (30800227), the Science and Technology Foundation of Guangdong Province (2009B030803057) and Guangdong Pharmaceutical University for financial support.

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Correspondence to Yun-Jun Liu, Hong-Liang Huang or Fu-Hai Wu.

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Liu, YJ., Liang, ZH., Li, ZZ. et al. 2-(3,5-Dibromo-4-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthrolinoruthenium(II) complexes: synthesis, characterization, cytotoxicity, apoptosis, DNA-binding and antioxidant activity. Biometals 23, 739–752 (2010). https://doi.org/10.1007/s10534-010-9340-2

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