Binding of Organometallic Ruthenium(II) and Osmium(II) Complexes to an Oligonucleotide: A Combined Mass Spectrometric and Theoretical Study

Ru(II) and Os(II) p-cymene dichloride complexes with either a pta (1,3,5-triaza-7-phosphatricyclo[]decane) or [pta-Me]Cl ligand which exhibit anticancer activity were prepd. and characterized by 1H and 31P NMR spectroscopy and mass spectrometry. Three of the complexes, viz. [Os(h6-p-cymene)Cl2(pta)] and [M(h6-p-cymene)Cl2(pta-Me)]Cl (M = Ru, Os), also were characterized by single-crystal x-ray diffraction. The pta complexes are selective anticancer agents, whereas the pta-Me+ complexes are indiscriminate and damage both cancer and healthy cells but represent models for the protonated pta adduct which was implicated in drug activity. To establish a link between their biol. activity and the effect they have on DNA (a likely in vivo target), the reactivity of the complexes toward a 14-mer oligonucleotide (5'-ATACATGGTACATA-3') was studied using electrospray ionization mass spectrometry. The complexes bind to the oligonucleotide with loss of chloride and in some cases loss of the arene. Loss of arene appears to be most facile with the Ru-pta complexes but also takes place with the Ru-pta-Me complexes, whereas arene loss is not obsd. for the Os complexes. As pH is reduced, increased binding to the oligonucleotide is obsd., as evidenced from mass spectrometric relative intensities. Binding energies between the metal centers and the surrounding ligands were calcd. using d. functional theory (DFT). The calcd. energies rationalize the exptl. obsd. tendencies for arene loss and show that the pta ligands are relatively strongly bound. Exchange of metal center (Ru vs. Os), methylation or protonation of the pta ligand, or change of the arene (p-cymene vs. benzene) results in significant differences in the metal-arene binding energies while leaving the metal-phosphine bond strength essentially unchanged. Significantly lower binding energies and reduced hapticity are predicted for the exchange of arene by nucleobases. The latter show higher binding energies for N s-bonding than for p-bonding. [on SciFinder (R)]

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Organometallics, 24, 9, 2114-2123

 Record created 2006-02-27, last modified 2018-03-08

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