Abstract
Knowledge of the nature of the bonding in organic and inorganic mercury compounds is important for understanding the mechanism of heavy metal poisoning. Thus, we have computed the Hg□L bond energies and formation free energies of organic and inorganic mercury complexes, [H3C□Hg□L]1+z and [H2O□Hg□L]2+z, with ligands of biological interest are predicted and rationalized using density functional theory. In contrast to the hard and soft acid and base principle, calculation of the Hg-L bond energies in the model organic and inorganic mercury complexes reveals that the soft metal center of Hg(II) prefers N ligands over S ligands. The result that the complexation energies in organic mercury compounds are less stable than inorganic analogues parallels the experimental findings of thermodynamically unstable Hg-C bond and kinetic lability of methylmercury cation. The concept of orbital-symmetry-based energy decomposition has been employed to determine the contributions from σ and π orbital interactions, electrostatics, and Pauli repulsion to the Hg-L bond energy. The calculations indicate that the bonding in the complexes with soft S ligands is more covalent than with hard N ligands by evaluating the electrostatic and the orbital interaction terms between the metal and ligand fragments. This remarkable result may help unravel the contradictory preference of Hg(II) for N ligands over S ligands. The stability of the complexes in different biological environments has been estimated systematically through the dependence of the dielectric constant □. In good agreement with experimentally observed high affinity for soft metal, MeS□□has been found to be the most thermodynamically preferable ligand for both mercury complexes. The factors governing metal cation selectivity by proteins are investigated. The finding that Hg can successfully compete with Zn in more solvent-exposed sites and in the reorganization of coordination modes may help predict the structural changes upon using Hg for determination of protein structures in X-ray crystallography. Moreover, the predicted geometries of organic and inorganic mercury complexes provide valuable knowledge in suggesting potential cellular targets and proposing possible mechanisms for the heavy metal poisoning in living cells for future studies.