Thiolate Bridging and Metal Exchange in Adducts of a Zinc Finger Model and Pt^II Complexes: Biomimetic Studies of Protein/Pt/DNA Interactions

To provide precedents for the possible interactions of platinum DNA adducts with zinc finger proteins, the complexes [Pt(dien)Cl]Cl (dien = diethylenetriamine) and [Pt(terpy)Cl]Cl (terpy = 2,2′:6′,2′′-terpyridine) were exposed to the N,N′-bis(2-mercaptoethyl)-1,4-diazacycloheptanezinc(II) dimer, [Zn(bme-dach)]2, and the products defined by electrospray ionization mass spectrometry (ESI−MS), X-ray crystallography and 195Pt NMR spectroscopy. The presence of a leaving chloride in both platinum(II) complexes facilitates electrophilic substitution involving sulfur-containing zinc finger synthetic models or, as in previous studies, zinc finger peptidic sequences. Monitored via ESI−MS, both reactants yielded evidence for Zn−(μ-SR)−Pt bridges followed by zinc ejection from the N2S2 coordination sphere and subsequent formation of a trimetallic Zn−(μ-SR)2−Pt−(μ-SR)2−Zn-bridged species. The isolation of Zn−(μ-SR)−Pt-bridged species [(Zn(bme-dach)Cl)(Pt(dien))]Cl is, to our knowledge, the first Zn−Pt bimetallic thiolate-bridged model demonstrating the interaction between Zn-bound thiolates and Pt2+. In the case of the [Pt(terpy)Cl]Cl reaction with the [Zn(bme-dach)]2, ESI−MS analysis further suggests metal exchange by formation of [Zn(terpy)Cl]+, whereas the [Pt(dien)Cl]Cl reaction does not yield the corresponding [Zn(dien)Cl]+ ion. Direct synthesis of the Zn−Pt thiolate-bridged species and the Pt(N2S2) chelate, where Pt has displaced the Zn from the chelate core, permitted the isolation of X-ray-quality crystals to confirm the bridging and metal-exchanged structures. The ESI−MS, 195Pt NMR spectroscopy, and molecular structures of the di- and trinuclear complexes will be discussed, as they provide insight into the metal-exchange mechanism.