Histidine Targeting Heterobimetallic Ruthenium(II)-Gold(I) Complexes

Inspired by the preferential, allosteric binding of RAPTA-T and auranofin to the nucleosome core particle, we describe the design and synthesis of a series of heterobimetallic ruthenium(II)-gold(I) complexes with varying spacer lengths ranging from four to eight polyethylene glycol units. Evaluation of their cytotoxicity reveals IC50 values in the low micromolar range against cisplatin sensitive and resistant human ovarian carcinoma (A2780, A2780cisR) and nontumoral human embryonic kidney (HEK293) cell lines. Binding studies monitored via mass spectrometry revealed an affinity for histidine residues on a fragment of the amyloid beta-protein (residues 1-16, employed as a model system), which is in accordance with the binding sites of parent drugs, RAPTA-C and auranofin, to the nucleosome core particle.