Mechanismic Investigation on the Cleavage of Phosphate Monoester Catalyzed by Unsymmetrical Macrocyclic Dinuclear Complexes: The Selection of Metal Centers and the Intrinsic Flexibility of the Ligand

Abstract

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.

1,8‐Bis(borylamido)naphthalene Complexes of Lithium and Zinc(II) Including a Zinc(II) Isocyanide Adduct

“…Zinc adducts supported by nitrogen based ligands in a 1,8‐naphthalene framework have attracted wide spread interest for the structures, catalytic, antioxidant, and antimicrobial properties , , , . The zinc complexes based on [1,8‐C 10 H 6 (NBNL) 2 ] 2– represent a new subcategory of this useful family of molecules.…”

Mechanistic Studies of Homo- and Heterodinuclear Zinc Phosphoesterase Mimics: What Has Been Learned?

“…Phosphomonoester hydrolysis by dizinc(II) complexes is usually studied using 4-nitrophenyl phosphate as an ester with a good leaving group (NPP, Figure 3). The mechanism of the hydrolysis of the NPP 2− dianion is generally believed to be concerted with a loose transition state, while for phosphomonoester monoanions a dissociative mechanism involving metaphosphate as the intermediate has not been ruled out (Cleland and Hengge, 2006; Klähn et al, 2006; Kamerlin and Wilkie, 2007; Zhang et al, 2014a,c; Sanyal et al, 2015). The dianion is less reactive than the monoanion due to the higher negative charge of the transition state.…”

“…The reaction kinetics showed a change in the reaction order at higher complex concentrations. Zhao and coworkers carried out DFT calculations to investigate the reaction mechanism (Zhang et al, 2014a,c). Different competitive catalytic mechanisms were found, depending on the concentration of the complex.…”

Macrocyclic Assembly: A Dive into the Pecking Order and Applied Aspects of Multitalented Metallomacrocycles

“…The form of the active catalyst has been verified, and the metal-bound ion acts as the nucleophilic reagent. The binding modes of the catalyst substrate complexes were also explored by Zhang and coworkers [99] (Figure 2). anion.…”