Novel Timine Ruthenium derivatives

Ruthenium complexes have proved to exhibit antineoplastic activity1,2 related to the interaction of metal ion with DNA nucleobases. It is indeed of great interest to provide new insights on theses cutting-edge studies such as the identification of different coordinative modes of DNA binding sites. This report deals with the reaction between dihydride Ruthenium complex [(PPh3)3Ru(CO)(H)2], 1, and the Thymine Acetic Acid N[CHC(CH3)C(O)NH]CH2C(O)OH THA, as model for nucleobases. The reaction of 1 with THA affords an unstable monohapto acetate hydride complex, which rapidly evolves into elusive intermediates whose nature was evidenced by NMR spectra and proposed by DFT calculation. Crystallizations enable to freeze the species [(PPh3)2Ru(CO)(1-THA)(2-THA)],4, adopting concomitant monohapto (1-O) in the species 2 and the chelate (2-O,O) coordinative fashion modes as in 3. Investigations by the analogue reactions of 1 with acetic acid confirmed the proposed mechanism. Further, the unexpected isolation of intermolecular dimeric crystalline species, [Ru(CO)(PPh3)2(2-N,O[THA(A)];1-O[THA(B)]]2, 3 whose X-ray structure, beside the monohapto acetate coordination, shows a reciprocal interannular four-membered (2-N,O) chelation. This fashion binding mode, displacing phosphine ligand, enables to stabilize the less stable tautomeric form (+10.1 kcalmol-1,calculated at B3LYP/Def2-TZVP level) of thymine. The spectroscopic features will be presented and discussed in comparison with X-ray molecular structures and DFT calculations.