Hydrolysis of Phosphate Triesters with Copper(II) Catalysts

Hydrolysis of diethyl 4-nitrophenyl phosphate (DEPNPP) to diethyl phosphate proceeds 1600-fold more rapidly with 1 mM Cu(bpy)²⁺at pH 6.4 and 75 °C than without metal complex catalyst. Cu(bpy)²⁺represents Cu(NO₃)₂and 2,2'-bipyridine in a 1:1 ratio in aqueous solution. Several Cu(II) complexes may be present under these conditions. These complexes are abbreviated as follows: Cu(bpy)(OH₂)²⁺is Cu(bpy)(OH₂)₄²⁺, Cu(bpy)(OH)⁺is Cu(bpy)(OH)(OH₂)₃⁺, Cu(bpy)₂²⁺is Cu(bpy)₂(OH₂)₂²⁺, and [Cu(bpy)(OH)]₂²⁺is [Cu(bpy)(OH₂)₂(μ-OH)]₂²⁺. Free copper(II) is abbreviated Cu²⁺. Ideal catalytic behavior was observed for two turnovers after which there was a gradual decrease in the rate of hydrolysis. Since addition of 4-nitrophenolate inhibits catalysis, the decrease in activity can be attributed to product inhibition. The rate exhibited a pH dependence with a kinetic pK_aof 6.9 ± 0.05, close to the first pK_aof Cu(bpy)(OH₂)²⁺. On the alkaline pH plateau the rate law was first order in Cu(bpy)²⁺and DEPNPP. A mechanism where Cu(bpy)(OH)⁺binds DEPNPP and bound OH^-attacks phosphorus is proposed. Isotopic labeling studies with¹⁸OH₂show that P-O cleavage occurs, which is consistent with nucleophilic displacement at phosphorus(V). The Cu(bpy)²⁺-catalyzed hydrolysis of DEPNPP is remarkable because (p-NO₂C₆H₄O)(C₂H₅O)PO₂^-is produced in 14-23% yield in addition to the expected (C₂H₅O)₂PO₂^-product. Since ethanol and 4-nitrophenol differ by 8 pK_aunits, one would expect to observe no product derived from ethoxide loss. A mechanism that involves metal- or proton-assisted binding of the alkoxide leaving group is proposed.