The biological inorganic chemistry of zinc ions

Abstract

The solution and complexation chemistry of zinc ions is the basis for zinc biology. In living organisms, zinc is redox-inert and has only one valence state: Zn(II). Its coordination environment in proteins is limited by oxygen, nitrogen, and sulfur donors from the side chains of a few amino acids. In an estimated 10% of all human proteins, zinc has a catalytic or structural function and remains bound during the lifetime of the protein. However, in other proteins zinc ions bind reversibly with dissociation and association rates commensurate with the requirements in regulation, transport, transfer, sensing, signalling, and storage. In contrast to the extensive knowledge about zinc proteins, the coordination chemistry of the “mobile” zinc ions in these processes, i.e. when not bound to proteins, is virtually unexplored and the mechanisms of ligand exchange are poorly understood. Knowledge of the biological inorganic chemistry of zinc ions is essential for understanding its cellular biology and for designing complexes that deliver zinc to proteins and chelating agents that remove zinc from proteins, for detecting zinc ion species by qualitative and quantitative analysis, and for proper planning and execution of experiments involving zinc ions and nanoparticles such as zinc oxide (ZnO). In most investigations, reference is made to zinc or Zn2+ without full appreciation of how biological zinc ions are buffered and how the d-block cation Zn2+ differs from s-block cations such as Ca2+ with regard to significantly higher affinity for ligands, preference for the donor atoms of ligands, and coordination dynamics. Zinc needs to be tightly controlled. The interaction with low molecular weight ligands such as water and inorganic and organic anions is highly relevant to its biology but in contrast to its coordination in proteins has not been discussed in the biochemical literature. From the discussion in this article, it is becoming evident that zinc ion speciation is important in zinc biochemistry and for biological recognition as a variety of low molecular weight zinc complexes have already been implicated in biological processes, e.g. with ATP, glutathione, citrate, ethylenediaminedisuccinic acid, nicotianamine, or bacillithiol.

Metal-coupled folding as the driving force for the extreme stability of Rad50 zinc hook dimer assembly

“…S3 and Fig. S4)1526. Both potentiometric and CD titrations of Hk peptides with Zn 2+ indicated that Zn 2+ -mediated dimers (Zn(Hk) 2 ) are formed preferentially at pH 7.4 (Fig.…”

Drawbacks of Dialysis Procedures for Removal of EDTA

“…For this we took advantage of the ability of the compound 4-(2-pyridylazo)-resorcinol (PAR) to form a colored 2:1 complex with zinc with high affinity (effective dissociation constant of the Zn(PAR) 2 complex, at pH 7.0, 2.1 x 10 −12 M 2 [17]), which presents an absorption maximum at 492 nm and can be measured spectrophotometrically. In turn, EDTA forms a 1:1 complex with zinc of extremely high affinity: 6 x 10 −14 M at pH 7.0 [18]. Therefore, solutions containing EDTA should compete with PAR for zinc binding, in such a way that the decrease in the absorption at 492 nm measured at the equilibrium can be used to infer the concentration of EDTA present in the sample.…”

Techniques for measuring cellular zinc

“…Below we turn to recent work that points to the need for careful controls in the application of these molecules and the importance of understanding of the underlying chemistry that allows these molecules to detect Zn 2+ . We also refer the reader to an excellent recent review that discusses the complex solution chemistry and speciation of zinc ions in biological environments [5]…”

“…Mammalian cells maintain a total concentration of Zn 2+ in the hundreds of micromolar [4]. While most of this Zn 2+ is bound to proteins and inaccessible, a pool of labile Zn 2+ , which is non-protein bound and complexed to a variety of small molecule ligands [5], has been detected in the cytosol with a concentration in the hundreds of picomolar. Furthermore, there is growing evidence of a labile Zn 2+ pool in organelles [4, 6].…”