The chemistry of Mg 2ϩ is unique among the biologically relevant cations. Compared with calcium, potassium, and sodium, Mg 2ϩ possesses the largest hydrated radius, the smallest ionic radius, and the greatest charge density (1). Its volume change from hydrated to atomic cation is almost 400-fold, whereas Ca 2ϩ , Na ϩ , and K ϩ are only 25-, 25-, and 4-fold, respectively. Waters of hydration are bound 3-4 orders of magnitude more tightly to Mg 2ϩ than to other common biological cations. The geometry of the hydration shell is octahedral with all six coordinate bond angles at angles of 90 Ϯ 6°. This contrasts with the far more flexible geometry of the Ca 2ϩ cation, which can tolerate bond angles of 90 Ϯ 35°(1-3).Study of Mg 2ϩ -dependent enzymes has revealed two types of interactions between Mg 2ϩ , enzymes, and ligands. Interaction can be through direct, inner sphere, coordination of a ligand to the metal ion or through an indirect, outer sphere, association with the bound water shell of the cation. In an outer sphere interaction, the relatively rigid geometry imposed by Mg 2ϩ