Enthalpic Control of Zinc—Water Acidity in Complexes of Tris(2-aminoethyl)amine and Tris(2-(dimethylamino)ethyl)amine

The enthalpies of ionization (AH_a) of zinc-bound water in the complexes [Zn(tren)(OH₂)]²⁺and [Zn(Me₆-tren)(OH₂)]²⁺have been determined by isothermal titration calorimetry and potentiometric methods in 1 M NaClO₄. The AG° (14.6 kcal/mol) for [Zn(tren)(OH₂)]²⁺is mainly due to large positive AH (11.0 kcal/mol), while that for [Zn(Me₆tren)(OH₂)]²⁺(12.1 kcal/mol) is attributable equally to positive AH (6.1 kcal/mol) and negative AS at 298 K. The increase in acidity of [Zn(Me₆tren)(OH₂)]²⁺relative to [Zn(tren)(OH₂)]²⁺corresponds to a AAG° of -2.5 kcal/mol. The AAH is —4.9 kcal/mol, and it is partially offset by a 2.4 kcal/mol contribution from A(TAS). These values differ from ones previously reported, particularly in that the thermodynamic basis of the increased acidity of the latter complex is not related to entropic effects, as was previously believed. Several possible origins of the enthalpic difference in the two ionization reactions are discussed. The results of the study invalidate the original data that led to the view that solvent structure mediates the pK_a of zinc-bound water in zinc hydrolytic enzymes.