Hydrolysis of Phosphate Diesters with Copper(II) Catalysts

Hydrolysis of phosphate diesters (4-NO₂C₆H₄O)₂PO₂Na (1) and (4-NO₂C₆H₄O)(CH₃CH₂O)PO₂Li (2) is catalyzed by Cu(bpy)²⁺(bpy = 2,2'-bipyridine) in aqueous solution at 75 °C in the pH range 5.8-8.3. Greater than 1000 turnovers and 200 turnovers per Cu(bpy)²⁺ are observed in the hydrolysis of 1 and 2, respectively. Catalytic rate enhancements of the hydrolysis of 1 and 2 by 1 × 10^-3 M Cu(bpy)²⁺ at pH 6.5 over spontaneous hydrolysis under the same conditions without catalyst are 2000 and 150, respectively. The hydrolysis of copper-bound 2 proceeds 6300-fold more rapidly (pH 7.85) than hydrolysis of 2 in the absence of catalyst. Kinetics for the Cu(bpy)²⁺-catalyzed hydrolysis of 2 are examined in detail. The pH-rate profile indicates two reaction pathways, hydrolysis with Cu(bpy)(OH)⁺ or its kinetic equivalent as the active catalyst at alkaline pH and less effective hydrolysis by Cu(bpy)²⁺ at low pH. Saturation kinetics follow Michaelis-Menton behavior (K_m = 4.7 × 10^-2 M, k_cat = 5.6 × 10^-4 s^-1) and provide evidence for the formation of a copper-phosphate ester complex, which decays to products. Labeling studies in ¹⁸OH₂show no incorporation of ¹⁸O into p-nitrophenol. A single ¹⁸O label incorporates into the (C₂H₅O)PO₃ ^2- product. Several simple transition-metal complexes promote the catalytic hydrolysis of phosphate diesters 1 and 2, although none are as effective as Cu(bpy)²⁺. Second-order rate constants for Cu(bpy)²⁺-promoted hydrolysis in the series of 4-nitrophenyl phosphate esters (triester, diester (anion), monoester (dianion)) vary by only a factor of 60 in contrast to those for the reaction of these phosphate esters with anionic nucleophiles in the absence of metal catalysts, which show large differences in second-order rate constants (>10³) between each ester in the series.