Theoretical studies of metal ion selectivity.: 2.: DFT calculations of complexation energies of selected transition metal ions (Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Hg2+) in metal-binding sites of metalloproteins

To obtain a deeper understanding of metal ion selectivity exhibited by different sites in biomolecules, the interactions of selected transition metal (TM) ions with model functional groups are further studied. The hypothesis is proposed that complexation energies of TM ions in metal-binding sites of a general formula [MXn](2+) can be estimated from the interaction energies of these ions with model functional groups X-i's and the quantitative evaluation of the cooperative effect. This effect is defined as the nonadditive part of the substitution energy of two functional groups for two water molecules in an [M(H2O)(n)](2+) complex (reference state) in comparison with the sum of the substitution energies of the respective monosubstitutions (defining the interaction energy of X-i). The model functional groups used for the evaluation of the cooperative effect are OH-, H2S, SH-, HCHO, HCOO-, NH3, and CH3NCH, Four coordination geometries (linear, tetrahedral, square planar, and octahedral), six transition metal ions (Co2+, Ni2+ Cu2+, Zn2+, Cd2+, Hg2+), and all combinations of the above functional groups are taken into account. To ascertain the plausibility of the hypothesis, complexation energies of TM ions in several model complexes [MXn](2+) are calculated and compared with their estimated values. It is shown that the consideration of the cooperative effect (i.e., the three-body X-i...M...X, interaction term) is both essential and sufficient to yield the estimates that deviate, on a relative scale, by less than 2%(5-15 kcal mol(-1)) from the calculated values. Finally, it is shown that the estimated (calculated) complexation energies of TM ions in metal-binding sites of two metalloproteins, carbonic anhydrase and carboxypeptidase A, are in a very good agreement with the experimentally determined stability constants.