Heterobimetallic propargyl gold complexes with π-bound copper or silver with enhanced anticancer activity

Abstract

Several propargyl functionalised substrates with different heteroatoms (N, O or S) have been used for the preparation of propargyl gold(I) phosphine complexes. The complexes were prepared in high yields either by reaction of the substrate with [Au(acac)PPh₃] or by reaction of [AuCl(PPh₃)] with potassium hydroxide and the substrate in methanol. Several of the complexes have been characterised by X-ray diffraction showing the presence of secondary bonds such as π-stacking and aurophilic interactions. The reaction of the propargyl gold(I) phosphine complexes with [Cu(NO₃)(PPh₃)₂] or [Ag(OTf)(PPh₃)₂] afforded heterobimetallic complexes with π-coordination of {Cu(PPh₃)₂} or {Ag(PPh₃)₂} to the alkyne bond. When the substituent of the propargyl unit contained more strongly coordinating pyridine moieties, [(PyCH₂)₂NCH₂CCAuPPh₃], coordination of the heterometal to the pyridine units occurred, displacing the phosphine groups and giving rise to a dimeric structure. The antiproliferative activity of the complexes against cisplatin resistant lung cancer cell line A549 was determined by MTT assay. The mononuclear gold complexes showed excellent activities with IC₅₀ values < 14 μM. Coordination of copper of silver to the alkynyl fragment resulted in a significant increase in activity suggesting a synergistic effect between the two metal centres.