The Uptake, Transport, and Storage of Nickel in Cells: A Modeling Study of MN2S2 Complexes and Their Derivatives

Abstract

Nickel is an essential metal in biological systems and numerous studies have investigated the import, regulation, utilization, and export in cells and the proteins involved. Coordination complexes of nickel have been aimed at providing background information on exchange of nickel from N-rich binding sites used for import and storage to S-rich sites of the active enzymes. The model compounds were used to investigate a range of metal exchange reactions that are plausible during nickel homeostasis in cells.

A comprehensive review has examined the MN2S2 complexes that have been synthesized-to-date and their structural aggregation properties when two to four metals bind to the available lone pair on the thiolate in MN2S2 complexes. The review summarized a wide range of modifications that are possible for MN2S2 complexes ranging from the metal used to the organic linker between the N and S donor atoms. The aggregation modes are largely determined by the coordination number preferences of the secondary metal(s). Another project attempted to quantify the electron donor properties and steric requirements of such MN2S2 metalloligands. Electronic donor properties were measured using the IR stretches in metal carbonyl reporter units. Attempts to quantify the spacial requirements of MN2S2 metalloligands were challenging due to the asymmetry of such ligands and several approaches were utilized such as the ligand cone angles (related to the famous Tolman cone angle) for monodentate binding, wedge angles for bidentate binding, or percent buried volume computations for both cases.

A series of MN2S2O2 complexes was synthesized and metal exchange properties examined. The complexes could be obtained from S-modification of MN2S2 compounds of from the free N2S2 ligand followed by metallation. The study showed the hierarchy of metal exchange followed the Irving-Williams series of stability for first row transition metals: Fe2+ < Co2+ < Ni2+ < Cu2+ > Zn2+. The mechanism of exchange appears to occur through a ligand unwrapping/wrapping process similar to the previously investigated M(EDTA) systems by Margerum in the 1960’s.

A wide range of biomimetic and inorganic compounds structures were solved using X-ray diffraction methods and figures for the finalized structures are presented.