Issue 8, 2015

Binding of an organo–osmium(ii) anticancer complex to guanine and cytosine on DNA revealed by electron-based dissociations in high resolution Top–Down FT-ICR mass spectrometry

Abstract

The OsII arene anticancer complex [(η6-bip)Os(en)Cl]+ (Os1-Cl; where bip = biphenyl, and en = ethylenediamine) binds strongly to DNA. Here we investigate reactions between Os1-Cl and the self-complementary 12-mer oligonucleotide 5′-TAGTAATTACTA-3′ (DNA12) using ultra high resolution Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS). Identification of the specific sites of DNA osmiation with {(η6-bip)Os(en)}2+ was made possible by the use of Electron Detachment Dissociation (EDD) which produced a wide range of assignable osmiated MS/MS fragments. In contrast, the more commonly used CAD and IRMPD techniques produced fragments which lose the bound osmium. These studies reveal that not only is guanine G3 a strong binding site for {(η6-bip)Os(en)}2+ but, unexpectedly, so too is cytosine C10. Interestingly, the G3/C10 di-osmiated adduct of DNA12 also formed readily but did not undergo such facile fragmentation by EDD, perhaps due to folding induced by van der Waal's interactions of the bound osmium arene species. These new insights into osmium arene DNA adducts should prove valuable for the design of new organometallic drugs and contribute to understanding the lack of cross resistance of this organometallic anticancer complex with cisplatin.

Graphical abstract: Binding of an organo–osmium(ii) anticancer complex to guanine and cytosine on DNA revealed by electron-based dissociations in high resolution Top–Down FT-ICR mass spectrometry

Supplementary files

Article information

Article type
Paper
Submitted
12 Dec 2014
Accepted
21 Jan 2015
First published
04 Feb 2015
This article is Open Access
Creative Commons BY license

Dalton Trans., 2015,44, 3624-3632

Binding of an organo–osmium(II) anticancer complex to guanine and cytosine on DNA revealed by electron-based dissociations in high resolution Top–Down FT-ICR mass spectrometry

C. A. Wootton, C. Sanchez-Cano, H. Liu, M. P. Barrow, P. J. Sadler and P. B. O'Connor, Dalton Trans., 2015, 44, 3624 DOI: 10.1039/C4DT03819C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements