Mapping the working route of phosphate monoester hydrolysis catalyzed by copper based models with special emphasis on the role of oxoanions by experimental and theoretical studies

Three copper(II) complexes derived from a reduced Schiff base ligand namely 4-bromo-2-[(2-hydroxy-1,1-dimethyl-ethylamino)-methyl]-phenol (H2L) were prepared by varying oxoanions (ClO4−, NO3−, OAc−) to explore the influence of anions on phosphatase activity and to explore the mechanistic pathway. Amongst the three complexes, complex 1 ([Cu4(L)2(HL)2(ClO4)2]·CH3OH) was reported earlier by us, whereas 2 ([Cu4(L)2(HL)2(NO3)2·C2H5OH·0.5H2O]) and 3 ([Cu4(L)2(HL)2 (OAc)2]·CH3CN·H2O) have been newly synthesized and structurally characterized by single crystal X-ray diffraction. The solution phase structure of the three complexes was determined by an ESI-MS technique. All the complexes (as dinuclear species) were able to hydrolyze the phosphate ester bond of 4-nitrophenylphosphate in a 97.5% N,N-dimethylformamide (DMF) medium and the rate of hydrolysis follows the trend 1 > 2 > 3. The intermediates formed during the reaction process were identified by means of ESI-MS study using the reaction mixture of complexes 1, 2 and 3. The detailed mechanistic pathway and role of oxoanions have been evaluated with the help of DFT calculations. The mechanism proposed for phosphatase activity by considering a dicopper complex without any oxoanion indicates the attack of the hydroxo ligand to the phosphate monoester as the rate-limiting step. The intermediates that were trapped experimentally match closely with the models proposed for the theoretical calculations. The extensive theoretical approach using a total of 36 model complexes and two possible mechanistic pathways proved that the presence of the oxoanion accelerates the hydrolysis of the phosphate ester bond and among the complexes studied the hydrolysis by the ClO4− derivative appears to be the most active.