Picture of wind turbine against blue sky

Open Access research with a real impact...

The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs.

The Energy Systems Research Unit (ESRU) within Strathclyde's Department of Mechanical and Aerospace Engineering is producing Open Access research that can help society deploy and optimise renewable energy systems, such as wind turbine technology.

Explore wind turbine research in Strathprints

Explore all of Strathclyde's Open Access research content

Penetrative DNA intercalation and G-base selectivity of an organometallic tetrahydroanthracene RuII anticancer complex

Liu, Hong-Ke and Parkinson, John and Bella, Juraj and Wang, Fuyi and Sadler, Peter (2010) Penetrative DNA intercalation and G-base selectivity of an organometallic tetrahydroanthracene RuII anticancer complex. Chemical Science, 1 (2). pp. 258-270. ISSN 2041-6520

[img]
Preview
PDF
ChemSci2010_1_258_270.pdf - Final Published Version

Download (350kB) | Preview

Abstract

The organometallic RuII arene complex [(eta6-tha)Ru(en)Cl]+ (1), where tha= tetrahydroanthracene and en= ethylenediamine, is potently cytotoxic towards cancer cells. We have used a combination of HPLC, ESI-MS, 1D- and 2D-NMR, including [1H, 1H] ROESY, NOESY, [1H, 15N] HSQC (using 15N-1), and [1H, 31P] experiments to elucidate the role of the non-aromatic, bulky rings of tha in adducts with the DNA hexamer d(CGGCCG), since DNA is a potential target for this drug. Reactions of 1 with single-stranded d(CGGCCG) gave rise to ruthenation at each of the three G bases, whereas reactions of the duplex d(CGGCCG)2 with 1 mol equiv. 1 led to exclusive ruthenation of G3 and G6 (and G9, G12) and not G2 (or G8). Addition of a second mol equiv. of 1 gave di-ruthenated adducts (major sites G3/G6, G6/G9, G2/G6), and on reaction with a third mol equiv. tri-ruthenation (G2, G3/G6/G12).The NMR data are indicative of the coordinative binding of Ru-tha specifically to G3 and G6, together with penetrative intercalation of the bulky non-coordinated tha rings B and C of 1′, selectively between two base pairs G3/C10:C4/G9 and G6/C7:C5/G8. Intercalation at GpC base steps by tha has a lower energy penalty compared to intercalation at GpG base steps, thereby allowing accommodation of tha. Monointercalation of tha reduced the strength of H-bonding between en-NH and GO6. These differences in structural distortions compared to cisplatin induced by the coordinative binding of Ru-tha to GN7 may contribute to the differences in mechanism of action, including protein recognition of the metallated lesions, and lack of cross resistance.