Stability and Mitochondrial Localization of a Highly Cytotoxic Organogold(III) Complex with Diphosphine Ancillary Ligand in Lung Cancer Cells.

We present a comprehensive study on the chemical reactivity in the gas phase, with amino acids and peptides, and in the cell, the anticancer activity and localization of a series of seven cationic biphenyl gold(III) complexes with aryl, alkyl, and chiral diphosphine ancillary ligands. Despite some structural differences, all the complexes similarly featured high stability toward reduction or ligand exchange in cell-free conditions. The biphenyl Au(III) complex including the 1,2-diphenylphosphinoethane (dppe) ligand manifested the same high stability in a cellular setting, as attested by a combination of cryo-Synchrotron Radiation-X-Ray Fluorescence (cryo-SR-XRF) nano-imaging and cryo-Synchrotron Radiation-X-ray Absorption Spectroscopy (cryo-SR-XAS) measurements. Tandem cryo-SR-XRF elemental mapping and confocal fluorescence microscopy demonstrated the selective accumulation of the dppe complex in mitochondria. This represents the first study of the speciation and distribution of an organogold(III) complex in cancer cells.