Metal ion selectivity of hydroxamates: A density functional study

First principles density functional calculations are performed on a number of square planar hydroxamate chelates of several divalent metal ions in order to determine their respective affinities for some biologically important ligands. The structures of the complexes are discussed, and the calculated binding mode is in agreement with experimental results. Extensive calculations have shown that, although the interactions are dominated mainly by electrostatic forces, there is a covalent contribution as well that introduces subtle variations in binding affinities of various metal ions. Thus, although a reasonable correlation is found between the complexation energies and reciprocals of the ionic radii of the metal ions, deviations may be attributed to some covalent character of the metal-ligand bonds, which modify a ligand's affinity for a metal ion and introduce subtle variations that are ultimately responsible for their biological action. A linear relationship between the partial charge on the metal ion and the LUMO energy shows that metal ions with lower lying vacant orbitals are able to form covalent coordination with the ligand. The affinity of the formohydroxamate ion for Ni(II) is satisfactorily explained on this basis. The bonding characteristics of the investigated complexes are discussed, as is the optimum size of the metal binding site. Some other hydroxamic acids are also investigated in this work. The electronic structures of urease from two microorganisms, and their acetohydroxamate complexes are also investigated in order to understand the inhibition mechanism. This study should prove useful not only for the understanding of coordination bonding, but also in the investigation of metalloenzymes and their inhibition.