Reactivity of NiII, PdII and PtII complexes bearing phosphine ligands towards ZnII displacement and hydrolysis in Cis2His2 and Cis3His zinc-fingers domains

Abstract

A systematic study of the effect of phosphine and bis-phosphine ligands in the interaction of Ni^II, Pd^II, and Pt^II complexes with two classes of zinc fingers was performed. The Cys₂His₂, finger 3 of specific protein-1, and the Cys₂HisCys C-terminal zinc finger of nucleocapsid protein 7 of the HIV-1 were used as models of the respective class. In general, phosphine ligands favor the metal binding to the peptide, although the bis-phosphine ligands produce more specific binding than the monodentate. In the case of nickel complexes, the interaction of Ni^II ions with the sequence SKH, present in Cys₂His₂, results in hydrolysis, contrasting to the preferred zinc ejection produced by the Ni^II complexes with chelating phosphines, producing Ni(bis-phosphine) fingers. In the absence of the SKH sequence, zinc ejection is observed with the formation of nickel fingers, with reactivity dependent on the phosphine. On the other hand, Pd(phosphines) produces Pd₂ fingers in the case of triphenylphosphine with the phosphine coordinated as intermediate species. The bis-phosphine ligands produce very clean spectra and a stable signal Pd(bis-phosphine)finger. Interestingly, phosphines produce very reactive platinum complexes, which eject zinc and promote peptide hydrolysis. The results reported here are relevant to the understanding of the mechanism of these interactions and how to modulate metallocompounds for zinc finger interference.

Keywords: Bioinorganic chemistry; Coordination chemistry; Mass spectrometry; Metal interaction; Phosphines; Zinc finger.