The hydrolysis mechanisms of phosphor-monoester monoanions NPP(-) (p-nitrophenyl phosphate) catalyzed by unsymmetrical bivalent dinuclear complexes are explored using DFT calculations in this report. Four basic catalyst-substrate binding modes are proposed, and two optional compartments for the location of the nucleophile-coordinated metal center are also considered. Five plausible mechanisms are examined in this computational study. Mechanisms 1, 2, and 3 employ an unsymmetrical dizinc complex. All three mechanisms are based on concerted SN2 addition-substitution pathways. Mechanism 1, which involves more electronegative oxygen atoms attached to the imine nitrogen atoms in the nucleophile-coordinated compartment, was found to be more competitive compared to the other two mechanisms. Mechanisms 4 and 5 are based on consideration of the substitution of the bivalent metal centers and the intrinsic flexibility of the ligand. Both mechanisms 4 and 5 are based on stepwise SN2-type reactions. Magnesium ions with hard base properties and more available coordination sites were found to be good candidates as a substitute in the M(II) dinuclear phosphatases. The reaction energy barriers for the more distorted complexes are lower than those of the less distorted complexes. The proper intermediate distance and a functional second coordination sphere lead to significant catalytic power in the reactions studied. More importantly, the mechanistic differences between the concerted and the stepwise pathways suggest that a better nucleophile with more available coordination sites (from either the metal centers or a functional second coordination sphere) favors concerted mechanisms for the reactions of interest. The results reported in the paper are consistent with and provide a reasonable interpretation for experimental observations in the literature. More importantly, our present results provide some practical suggestions for the selection of the metal centers and how to approach the design of a catalyst.

Density functional theory (DFT) was utilized to investigate the hydrolysis reaction mechanisms of phosphodiester BNPP (BNPP = bis(4-nitrophenyl)phosphate) catalyzed by a symmetrical oxyimine-based macrocyclic dinuclear zinc(ii) complex. We examined the nature of the nucleophilic reagent and the active form of the catalyst. The coordination and binding models of the catalyst-substrate complex were explored and we investigated two catalyst configurations (a ridge configuration and a plane configuration), four basic catalyst-substrate binding models (a mono-point-binding model, a dual-point-binding model, an OH-bridging model and a mono-center-dual-binding model) and two alternate roles for the metal-coordinated hydroxide ion (whether it acts as a nucleophile or as a general base to facilitate the deprotonation of a solvent molecule). The one-point-binding mode was found to be preferred to construct a starting reactant. Nine plausible reaction mechanisms were proposed and investigated. Mechanism 1, a stepwise SN2-type addition-substitution reaction involving a para-position nucleophilic attack and the configuration inversion of the phosphate, was found to be the most favorable pathway. All of the proposed pathways are derived from alternate mechanisms such as a ping-pong mechanism and an AP mechanism. The ping-pong mechanism in combination with the role of the metal-coordinated hydroxide ion acting as a nucleophile was found to be more competitive than the other mechanisms examined. Results reported in this paper are consistent with, and can be utilized to systematically interpret, the experimental observations in the literature.

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