Selective binding of an organoruthenium complex to G-rich human telomeric sequence by tandem mass spectrometry

Human telomeric DNA is reported to be a potential target for anticancer organometallic ruthenium(II) complexes, however, the interaction sites were not clearly discriminated and identified.

In the current study, tandem mass spectrometry (MS/MS) using collision-induced dissociation (CID) was firstly introduced to identify the interaction sites of an organometallic ruthenium(II) complex [(η⁶ -biphenyl)Ru(en)Cl][PF₆ ] (1; en = ethylenediamine) with 5'-T₁ T₂ A₃ G₄ G₅ G₆ -3' (I), the repeating unit of human telomeric DNA, in both positive- and negative-ion mode at a low reaction molar ratio (1/I = 0.2) which was applied to preserve the site selectivity.

Mass spectrometric results showed that mono-ruthenated I was the main product under the conditions. In positive-ion mode, MS/MS results indicated that ruthenium complex 1 binds to T₂ or G₆ in strand I. However, in negative-ion mode, no efficient information was obtained for exact identification of ruthenation sites which may be attributed to losses of fragment ions due to charge neutralization by the coordination of the positively charged ruthenium complex to the short MS/MS fragments.

This is the first report of using top-down MS to characterize the interactions of organometallic ruthenium(II) complexes and human telomeric DNA. Thymine can be thermodynamically competitive with guanine for binding to ruthenium complexes even at low reaction molar ratio, which inspired us to explore in greater depth the significance of thymine binding.