DEPROTONATION OF WATER IN THE PRESENCE OF CARBOXYLATE AND MAGNESIUM-IONS

The effects of a metal ion-bound carboxylate group on the acidity of a water molecule bound to the same cation have been assessed by ab init io molecular orbital calculations. In the hexahydrate Mg[H2O](6)(2+) t he free energy required to deprotonate one coordinated water molecule is only 40% of that required to deprotonate a free water molecule, ind icating that the presence of the magnesium ion facilitates the ionizat ion of water. However, if one of the water molecules in this hexahydra te Mg[H2O](6)(2+) is replaced by a carboxylate ligand, the energy requ ired to dissociate a proton from a metal ion-bound water molecule is i ncreased by approximately 80 kcal/mol and is intermediate between the energy required to deprotonate one water molecule in Mg[H2O](6)(2+) an d that for a free water molecule. This effect of the carboxylate group on the pK(a) of metal ion-bound water appears to be primarily the res ult of a reduction of the net positive charge of the overall Mg[H2O](5 )(2+)-(RCOO-) complex rather than any changes in the electronic struct ure of the magnesium cation itself, since a Mg2+-coordinated chloride ion has a similar influence on acidity. Two aquated magnesium-carboxyl ate motifs have been identified in crystal structures of small molecul es and in proteins. One is a magnesium-bound hydrated carboxylate moti f with an internal hydrogen bond. Formation of the hydrogen bond withi n this motif does not appear to appreciably affect the pK(a) of the me tal ion-bound water molecule. A major role of such a motif, found in m any protein crystal structures, may be to help align the rather rigid magnesium coordination octahedron, thus positioning appropriate functi onal groups for efficient catalytic activity. A second motif, which in volves a carboxylate group bound to two metal ion-bound water molecule s, is also found in several protein crystal structures. It is, however , more flexible in conformation than is the first motif and therefore cannot exert such rigid orientational powers. Thus, metal ion-bound wa ter molecules and carboxylate groups can interact in a synergistic fas hion to assist in the catalytic activity of enzymes by altering the pK (a) of the water molecule and by providing a means for aligning requir ed functional groups in a stereochemically precise manner (''coordinat ion clamping'').