Theoretical investigation of the reaction mechanism for the phosphatediesterhydrolysis using an asymmetric dinuclear metal complex as a biomimetic model of the purple acid phosphatase enzyme

In this work we have applied quantum mechanical calculations, at the density functional theory level, to investigate the phosphate diester hydrolysis promoted by a cationic heterodinuclear FeIII⋯ZnII complex that mimics the structural and functional properties of the purple acid phosphatase (PAP) enzymes. The hydrolysis of the dimethyl phosphate diester was investigated in the gas phase and in solution by means of the continuum PCM model, using the B3LYP hybrid exchange–correlation functional. Our computed results showed that the hydrolysis of the dimethyl phosphate ester takes place in two steps. The first step corresponds to a slow P–O bond formation through nucleophilic attack of the coordinated (FeIII)–OH group. The second step consists of a proton transfer process followed by the release of a methanol molecule. The first step is rate determining with activation free energy of 12.3 kcal mol−1, which is about 3 times lower than the activation free energy for the uncatalyzed reaction. We also show that the heterodinuclear site plays an important role favoring an associative mechanism for the phosphate diester hydrolysis, favoring the formation of a high energy intermediate phosphorane, and orienting the phosphate group to the nucleophilic attack.