X-ray diffraction studies on a series of cationic divalent metal nitrate complexes supported by the tris(1-isopropyl-4-tert-butylimidazolyl)phosphine ligand, {[Pim(Pri, But)]M(NO3)}(+) (M = Co, Cu, Zn, Cd, Hg), demonstrate that the nitrate ligand coordination mode is strongly dependent upon the metal. With the exception of that for the Hg-II derivative, the nitrate ligand coordination modes correlate with the activities of metal-substituted carbonic anhydrases, such that the only M-II-carbonic anhydrases which exhibit significant activity, i.e., the Zn and Co species, are those for which the {[Pim(Pri, But)]M(NO3)}(+) complexes possess strongly asymmetric nitrate ligands. This trend supports the notion that access to a unidentate, rather than a bidentate, bicarbonate intermediate may be a critical requirement for significant carbonic anhydrase activity. Interestingly, the nitrate coordination modes in the series of group 12 complexes, {[Pim(Pri, But)]M(NO3)}(+) (M = Zn, Cd, Hg), do not exhibit a monotonic periodic trend: the bidenticity is greater for the cadmium complex than for either the zinc or mercury complexes. Since Hg-II-carbonic anhydrase is inactive, the correlation between nitrate coordination mode and enzyme activity is anomalous for the mercury complex. Therefore, it is suggested that the inactivity of Hg-II-carbonic anhydrase may be a consequence of the reduced tendency of the mercury center in Hg-II-carbonic anhydrase to bind water.