Further Insight into the Lability of MeCN Ligands of Cytotoxic Cycloruthenated Compounds: Evidence for the Antisymbiotic Effect Trans to the Carbon Atom at the Ru Center

The two MeCN ligands in [Ru­(2-C6H4-2′-Py-κC,N)­(Phen, trans-C)­(MeCN)2]­PF6 (1), both trans to a sp2 hybridized N atom,
cannot be substituted by any other ligand. In contrast, the isomerized
derivative [Ru­(2-C6H4-2′-Py-κC,N)­(Phen, cis-C)­(MeCN)2]­PF6 (2),
in which one MeCN ligand is now trans to the C atom
of the phenyl ring orthometalated to Ru, leads to fast and quantitative
substitution reactions with several monodentate ligands. With PPh3, 2 affords [Ru­(2-C6H4-2′-Py-κC,N)­(Phen, cis-C)­(PPh3)­(MeCN)]­PF6 (3), in which PPh3 is trans to the C σ
bound to Ru. Compound 3 is not kinetically stable, because,
under thermodynamic control, it leads to 4, in which
the PPh3 is trans to a N atom of the Phen
ligand. Dimethylsulfoxide (DMSO) can also substitute a MeCN ligand
in 2, leading to 5, in which DMSO is coordinated
to Ru via its S atom trans to the N atom of the Phen
ligand, the isomer under thermodynamic control being the only compound
observed. We also found evidence for the fast to very fast substitution
of MeCN in 2 by water or a chloride anion by studying
the electronic spectra of 2 in the presence of water
or NBu4Cl, respectively. An isomerization related to that
observed between 3 and 4 is also found for
the known monophosphine derivative [Ru­(2-C6H4-2′-Py-κC,N)­(PPh3, trans-C)­(MeCN)3]­PF6 (10), in which
the PPh3 is located trans to the C of
the cyclometalated 2-phenylpyridine, since, upon treatment by refluxing
MeCN, it leads to its isomer 11, [Ru­(2-C6H4-2′-Py-κC,N)­(PPh3, cis-C)­(MeCN)3]­PF6. Further substitutions are also
observed on 11, whereby N^N chelates (N^N = 2,2′-bipyridine
and phenanthroline) substitute two MeCN ligands, affording [Ru­(2-C6H4-2′-Py-κC,N)­(PPh3, cis-C)­(N^N)­(MeCN)]­PF6 (12a and 12b). Altogether, the behavior of the obtained complexes by
ligand substitution reactions can be rationalized by an antisymbiotic
effect on the Ru center, trans to the C atom of the
cyclometalated unit, leading to compounds having the least nucleophilic
ligand trans to C whenever an isomerization, involving
either a monodentate or a bidentate ligand, is possible.