title: 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.
abstract: The two MeCN ligands in [Ru(2-C6H4-2'-Py-κC,N)(Phen, trans-C)(MeCN)2]PF6 (1), both trans to a sp(2) 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.
authors.forename: Ana Soraya Lima
authors.initials: AS
authors.lastname: Barbosa
authors.forename: Christophe
authors.initials: C
authors.lastname: Werlé
authors.affiliation: §Instituto de Química, UNAM, Circuito Exterior s/n, Ciudad Universitaria, Mexico, D. F. 04510, Mexico.
authors.forename: Claudia Olivia Oliva
authors.initials: CO
authors.lastname: Colunga
authors.affiliation: §Instituto de Química, UNAM, Circuito Exterior s/n, Ciudad Universitaria, Mexico, D. F. 04510, Mexico.
authors.forename: Cecilia Franco
authors.initials: CF
authors.lastname: Rodríguez
authors.affiliation: §Instituto de Química, UNAM, Circuito Exterior s/n, Ciudad Universitaria, Mexico, D. F. 04510, Mexico.
authors.forename: Ruben Alfredo
authors.initials: RA
authors.lastname: Toscano
authors.affiliation: §Instituto de Química, UNAM, Circuito Exterior s/n, Ciudad Universitaria, Mexico, D. F. 04510, Mexico.
authors.forename: Ronan
authors.initials: R
authors.lastname: Le Lagadec
authors.forename: Michel
authors.initials: M
authors.lastname: Pfeffer
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D010720:Phosphines / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D009942:Organometallic Compounds; D010720:Phosphines; D014867:Water; D002244:Carbon; D012428:Ruthenium; C044646:phosphine; D004121:Dimethyl Sulfoxide