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.本研究制备并考察了两种异构双核配体PBTPA、MBTPA及其铜(II)配合物对模型磷酸二酯底物双(对硝基苯基)磷酸酯的水解催化活性。铜(II)与PBTPA形成的双核配合物呈现钟形pH-反应速率曲线，该结果与双金属核酸酶/磷酸酶的已提出的催化机制一致。在pH 8.4条件下，其催化速率达到峰值1.14×10^-6 s^-1，较无催化反应速率提升逾10^4倍。然而，MBTPA对应的同类配合物未表现出显著的速率增强效果。铜(II)与PBTPA的双核配合物，其催化活性较铜(II)与三(2-吡啶甲基)胺(TPA)形成的单核配合物提升10倍。噬菌体φX174 DNA检测实验显示，铜(II)与PBTPA的配合物可在有氧及无氧条件下促进超螺旋噬菌体φX174 DNA的松弛反应，而铜(II)与TPA形成的单核配合物则无水解催化活性。