Fluorescent analogues of quinoline reveal amine ligand loss from cis and trans platinum(II) complexes in cancer cells

Analogues of cytotoxic cis and trans dichloridoplatinum(II) complexes with one ammonia and one aromatic amine (cis- and trans-[PtCl2(aromatic amine)(NH3)]) were synthesised in which the aromatic group was replaced by the fluorescent ligand 7-azaindole (1). Coordination resulted in almost complete quenching of the fluorescence and the ligand had a effect on the biological activities of the cis and trans isomers similar to that previously reported for aromatic amines as is exemplified by them having similar cytotoxicities (IC50 3.6(5) and 6.0(19) μM, respectively). Observation of fluorescence following treatment of the cis complex with cysteine, glutathione, or methionine suggests labilisation and subsequent loss of the putative non-leaving group ligands. No such effect was observed for the trans complex which does not experience trans labilisation. Two-photon excitation of cells that had been treated with the complexes gave rise to observable fluorescence, suggesting ligand displacement for both complexes. The fluorescence appears to be localised in the lysosomes or late endosomes. These complexes are excellent models of analogues of cytotoxic cis and trans complexes with aromatic amine ligands and can be used to study the metabolism of the non-leaving group positions.