Mechanistic Implications in the Phosphatase Activity of Mannich-Based Dinuclear Zinc Complexes with Theoretical Modeling

An “end-off” compartmental ligand has been synthesized by an abnormal Mannich reaction, namely, 2-[bis­(2-methoxyethyl)­aminomethyl]-4-isopropylphenol yielding three centrosymmetric binuclear μ-phenoxozinc­(II) complexes having the molecular formula [Zn₂(L)₂X₂] (<b>Zn-1</b>, <b>Zn-2</b>, and <b>Zn-3</b>), where X = Cl^–, Br ^–, and I ^–, respectively. X-ray crystallographic analysis shows that the ZnO₃NX chromophores in each molecule form a slightly distorted trigonal-bipyramidal geometry (τ = 0.55–0.68) with an intermetallic distance of 3.068, 3.101, and 3.083 Å (<b>1</b>–<b>3</b>, respectively). The spectrophotometrical investigation on their phosphatase activity established that all three of them possess significant hydrolytic efficiency. Michaelis–Menten-derived kinetic parameters indicate that the competitiveness of the rate of P–O bond fission employing the phosphomonoester (4-nitrophenyl)­phosphate in 97.5% <i>N</i>,<i>N</i>-dimethylformamide is <b>3</b> > <b>1</b> > <b>2</b> and the <i>k</i>_cat value lies in the range 9.47–11.62 s^–1 at 298 K. Theoretical calculations involving three major active catalyst forms, such as the dimer-cis form (D-Cis), the dimer-trans form (D-Trans), and the monoform (M-1 and M-2), systematically interpret the reaction mechanism wherein the dimer-cis form with the binuclear-bridged hydroxide ion acting as the nucleophile and one water molecule playing a role in stabilizing the leaving group competes as the most favored pathway