Thermodynamic stability versus kinetic lability of ZnS₄ core

Density Functional Theory and post-Hartree Fock calculations reveal an unusual energy profile for Zn-S and Zn-N bond dissociation reactions in several [Zn(SR)₄]^2- and [Zn(Im)(SR)₃]^- complexes. The Zn-S bond dissociation in tetrathiolate dia- nions, which is highly exothermic in the gas phase, proceeds through a late transition state which can be rationalized on the basis of an avoided crossing resulting from Coulomb repulsion between the anionic fragments and ligand-to-metal charge-transfer in the Zn(SR)₄]^2- complexes. When solvation models for water, DMSO, or acetoni- trile are included, some complexes become stable while others are meta- stable, so this constitutes the first theoretical model which is in full agreement with the experimental data for various Zn(SR)₄]^2-, Zn(SR)₃]^- and Zn(SR)₃]^- complexes. The analysis given here indicates that the Zn- (Cys)₄ and Zn(His)(Cys)₃ cores of numerous proteins are metastable with respect to Zn-S and Zn-N bond dissociation, respectively. This is consistent with the kinetic lability at the zinc-centers and illustrates that in nature, ther- modynamic stability is imparted upon the zinc cores by the protein environment.