Ru(II), Os(II) and RH(III) complexes of PTA : their reactivity towards nucleotides and oligonucleotides

A series of ruthenium, osmium and rhodium complexes utilizing pta, (1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane) and pta-Me+, its N-methyl derivative, have been synthesized. Their characterization by 1H and 31P NMR spectroscopy, ESI-MS and single crystal X-Ray diffraction are described. The mechanism of hydrolysis for [Ru(η6-C10H14)Cl2(pta)] has been studied and two watertype adducts, [Ru(η6-C10H14)Cl(OH2)(pta)][Cl] and [Ru(η6-C10H14)(OH2)2(pta)][Cl]2, have been characterized by 1H and 31P NMR spectroscopy and ESI-MS. The pKa of the pta moiety for the mono-aqua complex has been determined to be 2.33 ± 0.07, and the one of bis-aqua estimated to be between 2 and 2.1 units of pH. Although it was not possible to measure the pKa of the coordinated water, it is expected to be higher than 8 for the mono-aqua and 6.5 for the bis-qua complexes. The reactivity of the above described complexes towards guanine and adenine in which N9 position is blocked by a methyl or ribose substituent, has been investigated. The coordination of the complexes through the N7 center has been demonstrated by 1H NMR spectroscopy, and ESI-MS, which has also shown the formation of η2-(N6,N7) coordination mode for the adenine derivatives. The pKa for [Ru(η6-C10H14)Cl2(guanosine)(pta)] has been determined as 2.54 ± 0.03. A second model was devised based on a 14-mer strand (5'-ATACATGGTACATA-3') and ESI-MS has been used to demonstrate specific reactivity of the complexes. The interaction of pta and pta derivatives has been confirmed, however, no correlation between the reactivity toward the DNA strand and antineoplastic activity was found. Ruthenium, especially with hydrogen bonding capable substituents, is able to dissociate the arene group, which is not observed for the osmium cases, and it is believed that the water solubility of the arene, rather the strength of the arene – ruthenium bond plays more of a role.