Jump to main content
Jump to site search
PLANNED MAINTENANCE Close the message box

Scheduled maintenance work on Wednesday 27th March 2019 from 11:00 AM to 1:00 PM (GMT).

During this time our website performance may be temporarily affected. We apologise for any inconvenience this might cause and thank you for your patience.


Issue 11, 2017
Previous Article Next Article

Interstrand DNA covalent binding of two dinuclear Ru(II) complexes. Influence of the extra ring of the bridging ligand on the DNA interaction and cytotoxic activity

Author affiliations

Abstract

In this work, we report experimental and computational evidence for the intercalation into the DNA base-pairs of the free quinones quinizarin (Q) and naphthazarin (N) and the interstrand covalent binding of their p-cymene di-ruthenium(II) complexes (Cl2Ru2X, with X = N, Q bridging ligands). The intercalation extent for the N complex was larger than that for Q, which is in good agreement with the higher relative contour length and melting temperature for the same CX/CDNA ratio and with the computational mean stacking distances between the ligand and the nearest base-pair (3.34 Å and 3.19 Å) for N and Q, respectively. However, the apparent binding constant of Q/DNA, two orders higher than that of N/DNA, indicates that the thermal stability of the X/DNA complex is more related to the degree of intercalation than to the magnitude of the binding constant. Cl2Ru2X complexes undergo aquation, forming the aqua-derivatives [(H2O)2Ru2X]2+. These can further bind covalently to DNA via interstrand crosslinking, through both Ru centres and two N7 sites of consecutive guanines, to give (DNA1,2)Ru2X complexes, by a mechanism similar to that of cisplatin. To the best of our knowledge, this type of interaction with dinuclear Ru(II) complexes has not been reported hitherto. The experimental and computational results reveal that the number of rings of the aromatic moiety and the covalent binding to DNA play a key role in the behaviour of the quinones and their Ru(II) derivatives. The cytotoxicity of the ligands and the corresponding Ru(II) complexes was evaluated in MCF-7, A2780, A2780cis tumour cells and in the healthy cell line MRC-5. The cytotoxic activity was notable for N and negligible for Q. The IC50 values and the resistance (RF) and selectivity (SF) factors show that the Cl2Ru2N complex is the most promising among the four studied anticancer drugs.

Graphical abstract: Interstrand DNA covalent binding of two dinuclear Ru(ii) complexes. Influence of the extra ring of the bridging ligand on the DNA interaction and cytotoxic activity

Back to tab navigation

Supplementary files

Publication details

The article was received on 27 Dec 2016, accepted on 14 Feb 2017 and first published on 15 Feb 2017


Article type: Paper
DOI: 10.1039/C6DT04888A
Citation: Dalton Trans., 2017,46, 3611-3622

  •   Request permissions

    Interstrand DNA covalent binding of two dinuclear Ru(II) complexes. Influence of the extra ring of the bridging ligand on the DNA interaction and cytotoxic activity

    H. J. Lozano, N. Busto, G. Espino, A. Carbayo, J. M. Leal, J. A. Platts and B. García, Dalton Trans., 2017, 46, 3611
    DOI: 10.1039/C6DT04888A

Search articles by author

Spotlight

Advertisements