Journal
DALTON TRANSACTIONS
Volume 44, Issue 8, Pages 3624-3632Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c4dt03819c
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Funding
- Warwick Centre for Analytical Science (EPSRC) [EP/F034210/1]
- European Research Council [247450]
- Bruker Daltonics
- Warwick Collaborative Postgraduate Research Scholarships (WCPRS)
- Key International (Regional) Joint Research Program of NSF [2014456]
- National Science Foundation (NSF) [21171095]
- Engineering and Physical Sciences Research Council [EP/J000302]
- EPSRC [EP/J000302/1, EP/F034210/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [EP/J000302/1, EP/F034210/1] Funding Source: researchfish
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The Os-II arene anticancer complex [(eta(6)-bip)Os(en)Cl](+) (Os1-Cl; where bip = biphenyl, and en = ethylene-diamine) 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 {(eta(6)-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 G(3) a strong binding site for {(eta(6)-bip)Os(en)}(2+) but, unexpectedly, so too is cytosine C-10. Interestingly, the G(3)/C-10 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.
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