Ab initio study of Cd–thiol complexes: application to the modelling of the metallothionein active site

The metallothionein active site in vacuo was studied using ab initio methods as a necessary step in order to understand the relationship between the structure and the efficiency of the protein in binding cadmium ions. The natural Cd₄Cys₁₁ cluster located in the protein α-domain was represented by cadmium–thiolate complexes. First, it was shown, by comparison with available experimental results, that the geometry and the binding energy of cadmium coordination complexes can be correctly predicted at the RHF-MP2 theory level using the effective core potentials (ECP) and the double-ζ basis sets of Hay–Wadt, improved with polarization and diffuse functions. The computed geometry of the model system of the α-domain active site was then compared with that extracted from the X-ray crystal structure of the metallothionein. The significant difference between the two structures was attributed to the external constraints imposed in the natural cluster by the surrounding protein structure. The nature of the Cd–thiolate bond was further examined by calculating natural atomic populations and localizing the molecular orbitals. A good correlation between the Cd–S bond length and the amount of charge transferred from the ligand to the cadmium ion was found allowing an explanation of the effects of ligand protonation on the structure of mixed cadmium–thiol/thiolate complexes.