Binding of DNA purine sites to dirhodium compounds probed by mass spectrometry

The adducts formed between the antitumor active compounds [Rh-2(O2CCH3)(2)(CH3CN)(6)](BF4)(2), Rh-2(O2CCH3)(4), and Rh-2(O2CCF3)(4) with DNA oligonucleotides have been assessed by matrix-assisted laser desorption ionization (MALDI) and nanoelectrospray (nanoESI) coupled to time-of-flight mass spectrometry (TOF MS). A series of MALDI studies performed on dipurine (AA, AG, GA, and GG)-containing single-stranded oligonucleotides of different lengths (tetra-to dodecamers) led to the establishment of the relative reactivity cis-[Pt(NH3)(2)(OH2)(2)](2+) (activated cisplatin) approximate to Rh-2(O2CCF3)(4) > cis-[Pt(NH3)(2)Cl-2] (cisplatin) much greater than [Rh-2(O2CCH3)(2)(CH3CN)(6)](BF4)(2) > Rh-2(O2CCH3)(4) approximate to Pt(C6H6O4)(NH3)(2) (carboplatin). The relative reactivity of the complexes is associated with the lability of the leaving groups. The general trend is that an increase in the length of the oligonucleotide leads to enhanced reactivity for Rh-2(O2CCH3)(2)(CH3CN)(6)](BF4)(2) and Rh-2(O2CCH3)(4) (except for the case of [Rh-2(O2CCH3)(2)(CH3CN)(6)](2+), which reacts faster with the GG octamers than with the dodecamers), whereas the reactivity of Rh-2(O2CCF3)(4) is independent of the oligonucleotide length. When monitored by ESI, the dodecamers containing GG react faster than the respective AA oligonucleotides in reactions with Rh-2(O2CCF3)(4) and Rh-2(O2CCH3)(2)(CH3CN)(6)](BF4)(2), whereas AA oligonucleotides react faster with Rh-2(O2CCH3)(4). The mixed (AG, GA) purine sequences exhibit comparable rates of reactivity with the homopurine (AA, GG) dodecamers in reactions with Rh2(02CCH3)4. The observation of initial dirhodium-DNA adducts with weak axial (ax) interactions, followed by rearrangement to more stable equatorial (eq) adducts, was achieved by electrospray ionization; the Rh-Rh bond as well as coordinated acetate or acetonitrile ligands remain intact in these dirhodium-DNA adducts. MALDI in-source decay (ISD), collision-induced dissociation (CID) MS-MS, and enzymatic digestion studies followed by MALDI and ESI MS reveal that, in the dirhodium compounds studied, the purine sites of the DNA oligonucleotides interact with the dirhodium core. Ultimately, both MALDI and ESI MS proved to be complementary, valuable tools for probing the identity and stability of dinuclear metal-DNA adducts.