New 7-azaindole palladium and platinum complexes: crystal structures and theoretical calculations. In vitro anticancer activity of the platinum compounds

• Published in: Dalton transactions : an international journal of inorganic chemistry Vol. 39; no. 13; pp. 3290 - 3301
• Main Authors: Ruiz, José, Rodríguez, Venancio, de Haro, Concepción, Espinosa, Arturo, Pérez, José, Janiak, Christoph
• Format: Journal Article
• Language: English
• Published: England 01.01.2010
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; Cell Line, Tumor; Circular Dichroism; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - toxicity; Crystallography, X-Ray; DNA Adducts - chemistry; Humans; Hydrogen Bonding; Indoles - chemistry; Kinetics; Molecular Conformation; Palladium - chemistry; Platinum - chemistry; Thermodynamics
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/b920854b

A series of new 7-azaindolyl palladium and platinum complexes have been prepared. The X-ray structure determinations of [NBu(4)][M(C(6)F(5))(2)(Haza-N7)(aza-N1)].Haza [M = Pd, Pt; aza = 7-azaindolate (lH-pyrrolo[2,3-b]pyridinate)] have established for the first time the coordination to the same metal centre of both neutral and anionic forms of the ligand. Theoretical calculations at the mPW1B95/aug6-31G**/StRSCecp level show that both kinetic and thermodynamic arguments support the observed coordination and H-bonding interaction of the pyrrolo and pyridine moieties of the neutral and deprotonated heterocyclic ligands. At 48 h incubation time the new platinum complex [Pt(dmba)(aza-N1)(DMSO)] (dmba = N,N-dimethylbenzylamine-kappaN,kappaC) shows sub-micromolar activity both in A2780 and T47D [IC(50) (microM) = 0.34 and 0.53, respectively]. The DNA adduct formation of the new platinum complexes was followed by circular dichroism and electrophoretic mobility.