title: Isomerization of platinum-coordinated iminoethers induced by spectator ligands: stabilization of the Z anti configuration.
abstract: Iminoether derivatives of the formula trans-[PtCl2{HN═C(R)OR'}2] proved to be endowed with remarkable antitumor activity in vivo. Moreover, these trans compounds were more cytotoxic than their cis congeners, a trend opposite to that generally observed for corresponding platinum complexes with ammines. The imino ligands can have either E or Z configuration about the C═N double bond, and in the case of R = R' = Me, the E configuration is by far thermodynamically preferred. However, substitution of chloride anions with neutral ligands (L) alters the relative stability of the E and Z isomers. Upon investigation of the derivatives with L = PPh3, AsPh3, Me2S═O, and (H2N)2C═S, it has been concluded that an electrostatic interaction between the oxygen lone pair of the iminoether and the platinum center, fostered by the net positive charge of the complex and the low dielectric constant around the metal core provided by the hydrophobic L ligands, stabilizes the Z configuration. The same factors can favor iminoether isomerization. These conclusions are fully supported by X-ray crystal data. In the case of a reaction with thiourea, an aminic group of thiourea can substitute the methoxy group of a cis-iminoether, leading to the formation of a cyclic compound in a process reminiscent of the McLafferty rearrangement. Such a rearrangement could play a role in the interaction of the platinum-iminoether compounds with target DNA and proteins.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro , via E. Orabona 4, 70125 Bari, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Giardina-Papa
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Intini
authors.forename: Concetta
authors.initials: C
authors.lastname: Pacifico
authors.forename: Giovanni
authors.initials: G
authors.lastname: Natile
mesh_terms: D018360:Crystallography, X-Ray; D007097:Imines / Q000737:chemistry*; D007536:Isomerism; D008958:Models, Molecular; D009944:Organoplatinum Compounds / Q000737:chemistry*; D013890:Thiourea / Q000737:chemistry
chemical_list: D007097:Imines; D009944:Organoplatinum Compounds; D013890:Thiourea