Issue 13, 2011

Interaction of rac-[M(diimine)3]2+ (M = Co, Ni) complexes with CT DNA: role of 5,6-dmp ligand on DNA binding and cleavage and cytotoxicity

Abstract

The complexes [Co(diimine)3](ClO4)21–3 and [Ni(diimine)3](ClO4)24–6, where diimine = 1,10-phenanthroline (phen) (1,4), 5,6-dimethyl-1,10-phenanthroline (5,6-dmp) (2,5) and dipyrido[3,2-d:2′,3′-f]quinoxaline (dpq) (3,6), have been isolated, characterized and their interaction with CT DNA studied by using a host of physical methods. The X-ray crystal structures of rac-[Co(5,6-dmp)3](ClO4)22 and rac-[Ni(5,6-dmp)3](ClO4)25 have been determined and the isostructural and also isomorphous complex cations possess distorted octahedral coordination geometries. The absorption spectral titrations of the complexes with DNA reveal that the CT DNA binding affinity (Kb) of the complexes varies as 3 > 2 > 1; 6 > 5 > 4. The Ni(II) complexes display DNA binding stronger than the corresponding Co(II) analogues, which is expected of their bigger sizes. The higher DNA binding affinity of 3 and 6 is due to the involvement in partial insertion of the extended phen ring in between the DNA base pairs. In contrast, 2 and 5 interact with DNA in the major groove through hydrophobic forces involving the methyl groups on the 5,6 positions of phen ring. An enhancement in relative viscosities of DNA upon binding to 1–6 is consistent with the DNA binding affinities. The CD spectral studies show only an induced CD band on the characteristic positive band of CT DNA for both the phen (1,4) complexes. In contrast, the 5,6-dmp (2,5) and dpq (3,6) complexes bound to CT DNA exhibit biphasic CD signals in place of the positive CD band and the negative helicity band disappears. This reveals that the complexes bind to DNA enantiopreferentially and effect changes in secondary structure of DNA. The CV and DPV responses indicate that the DNA-bound dpq complexes are stabilized in the lower oxidation state of Co(II) more than in the Co(III) oxidation state. The prominent DNA cleavage abilities of 1–3 observed in the presence of H2O2 (200 μM) follows the order 2 > 1 > 3 with efficiencies of more than 90% even at 10 μM complex concentration. Interestingly, Ni(II) complexes 4–6 exhibit higher cytotoxicity (IC50: 1, 28.0; 2, 15.0; 3, 20.0; 4, 8.0; 5, 2.0; 6, 2.0 μM at 48 h; IC50: 1, 30.0; 2, 20.0; 3, 25.0; 4, 10.0; 5, 3.0; 6, 3.0 μM at 24 h) against human breast cancer (MCF 7) cell lines than the Co(II) complexes 1–3 as well as cisplatin in spite of their inability to cleave DNA. Also, the 5,6-dmp complex 5 shows cytotoxicity higher than the dpq complex 6 at 24 h incubation time and both 5 and 6 display apoptotic and necrotic modes of cell death.

Graphical abstract: Interaction of rac-[M(diimine)3]2+ (M = Co, Ni) complexes with CT DNA: role of 5,6-dmp ligand on DNA binding and cleavage and cytotoxicity

Supplementary files

Article information

Article type
Paper
Submitted
08 Oct 2010
Accepted
12 Jan 2011
First published
28 Feb 2011

Dalton Trans., 2011,40, 3245-3256

Interaction of rac-[M(diimine)3]2+ (M = Co, Ni) complexes with CT DNA: role of 5,6-dmp ligand on DNA binding and cleavage and cytotoxicity

S. Ramakrishnan, E. Suresh, A. Riyasdeen, M. A. Akbarsha and M. Palaniandavar, Dalton Trans., 2011, 40, 3245 DOI: 10.1039/C0DT01360A

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