Structural Characterization, Solution Studies and DFT Calculations on a Series of Binuclear Gold(III) Oxo Complexes: Relationships to Biological Properties

A series of structurally related oxo-bridged binuclear gold(III) compounds, [Au2(μ-O)2(N^N)2](PF6)2, where N^N is 2,2′-
bipyridine or a substituted 2,2′-bipyridine, have recently been shown to exhibit appreciable stability under physiologicallike
conditions and to manifest important antiproliferative effects toward selected human tumor cell lines (J. Med. Chem.
2006, 49, 5524). The crystal structures of four members of this series, namely, [Au2(μ-O)2(bipy)2](PF6)2, cis-[Au2(μ-O)2(6-
Mebipy)2](PF6)2, trans-[Au2(μ-O)2(6-oXylbipy)2](PF6)2, and [Au2(μ-O)2(6,6′-Me2bipy)2](PF6)2, have been solved here and
the respective structural parameters comparatively analyzed. Remarkably, all of the compounds contain a common structural
motif consisting of a Au2O2 “diamond core” linked to two bipyridine ligands in a roughly planar arrangement. Interestingly,
introduction of different kinds of alkyl or aryl substituents on the 6 (and 6′) position(s) of the bipyridine ligand leads to
small structural changes that nonetheless greatly affect the reactivity of the metal centers. The chemical behavior of
these compounds in solution has been studied in detail, focusing in particular on the electrochemical properties. Some
initial correlations among the structural parameters, the chemical behavior in solution, and the known cytotoxic effects of
these compounds are proposed. Notably, we have found that the 6,6′-dimethyl-2,2′-bipyridine derivative, which showed
the largest structural deviations with respect to the model compound [Au2(μ-O)2(bipy)2](PF6)2, also had the highest oxidizing
power, the least thermal stability, and the greatest cytotoxic activity. The positive correlation that exists between the
oxidizing power and the antiproliferative effects seems to be of particular interest. Moreover, the electronic structures of
these compounds were extensively analyzed using DFT methods, and the effects of the various substituents on reactivity
were predicted; overall, very good agreement between theoretical expectations and experimental data was achieved. In
turn, theoretical predictions offer interesting hints for the design of new, more active binuclear gold(III) compounds.