title: Thiolate bridging and metal exchange in adducts of a zinc finger model and Pt(II) complexes: biomimetic studies of protein/Pt/DNA interactions.
abstract: 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 (195)Pt 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-(mu-SR)-Pt bridges followed by zinc ejection from the N2S2 coordination sphere and subsequent formation of a trimetallic Zn-(mu-SR)2-Pt-(mu-SR)2-Zn-bridged species. The isolation of Zn-(mu-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 Pt(2+). 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, (195)Pt NMR spectroscopy, and molecular structures of the di- and trinuclear complexes will be discussed, as they provide insight into the metal-exchange mechanism.
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, Texas 77843, USA.
authors.forename: Elky
authors.initials: E
authors.lastname: Almaraz
authors.forename: Queite A
authors.initials: QA
authors.lastname: de Paula
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Reibenspies
authors.forename: Marcetta Y
authors.initials: MY
authors.lastname: Darensbourg
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Farrell
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry; D002945:Cisplatin / Q000031:analogs & derivatives / Q000737:chemistry; D018736:DNA Adducts / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D009944:Organoplatinum Compounds / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry; D016335:Zinc Fingers
chemical_list: D018736:DNA Adducts; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D013438:Sulfhydryl Compounds; C032799:chlorodiethylenetriamine platinum; D010984:Platinum; C021975:chloroterpyridineplatinum(II); D015032:Zinc; D002945:Cisplatin