Geometry-Dependent Phosphodiester Hydrolysis Catalyzed by Binuclear Copper Complexes

Two isomeric binuclear ligands PBTPA and MBTPA and their copper(II) complexes were prepared and examined
for hydrolysis of a model phosphodiester substrate:  bis(p-nitrophenyl)phosphate. A bell-shaped pH vs rate profile,
which is in agreement with one mechanism proposed for bimetallonucleases/phosphatases, was observed for the
binuclear complex of copper(II) and PBTPA. At pH 8.4, a maximum rate of 1.14 × 10-6 s-1more than 104-fold
over uncatalyzed reactionswas achieved. However, the analogous complex of MBTPA did not show significant
rate enhancement. The binuclear complex of copper(II) and PBTPA also showed 10-fold acceleration over
mononuclear complex of copper(II) and tris(2-pyridylmethyl)amine (TPA) catalyzed reaction. A phage φX174 DNA
assay showed that the complex of copper(II) and PBTPA promoted supercoiled phage φX174 DNA relaxation
under both aerobic and anaerobic conditions, in contrast to the hydrolytic inactivity of the mononuclear complex of
copper(II) and TPA.