A theoretical study of Zn++ interacting with models of ligands present at the thermolysin active site.

The binding energy and the geometrical arrangements of the complexes formed by the zinc dication with OH-, one, four, five or six water molecules, SH-, H2S, formic acid, the formate anion, imidazole, its anion and formamide are calculated using the MNDO method. The comparison of the results obtained with those of ab initio computations on the same complexes induced us to propose for Zn++ a set of parameters different from the one determined by Dewar for the neutral metal atom. Using the two MNDO parametrizations, similar calculations are carried out for Zn++ interacting with two molecules of 2-aminoethanethiol and with models of the four ligands which are present at the thermolysin active site, in order to evaluate the possibilities and limitations of this semiempirical method for theoretical studies concerning zinc metalloenzymes. In the last case, the results obtained suggest that, in the crystal state, the water molecule could be deprotonated. This finding is discussed in relation with the mechanism of action of the enzyme which has been proposed.