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

• Published in: Inorganic chemistry 2015-08, Vol.54 (15), p.7617-7626
• Main Authors: Barbosa, Ana Soraya Lima, Werlé, Christophe, Colunga, Claudia Olivia Oliva, Rodríguez, Cecilia Franco, Toscano, Ruben Alfredo, Le Lagadec, Ronan, Pfeffer, Michel
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Carbon; Carbon - chemistry; Coordination compounds; Dimethyl Sulfoxide - chemistry; Isomerization; Isomers; Ligands; Models, Molecular; Molecular Conformation; Nuclei; Organometallic Compounds - chemistry; Phosphines - chemistry; Ruthenium - chemistry; Stereoisomerism; Substitution reactions; Thermodynamics; Water - chemistry
• ISSN: 0020-1669; 1520-510X
• DOI: 10.1021/acs.inorgchem.5b01236

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.