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

Abstract

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] (Zn-1, Zn-2, and Zn-3), 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 (1-3, 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% N,N-dimethylformamide is 3 > 1 > 2 and the kcat 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.

Investigation of the identity of the nucleophile initiating the hydrolysis of phosphate esters catalyzed by dinuclear mimics of metallohydrolases

“…Density functional theory calculations have previously been used to study phosphate and amide hydrolysis by related dizinc complexes [21,40,41,85,86,87,88,89].…”

Synthesis and characterization of phenoxo-bridged dinuclear zinc(II) halide complexes: Role of electron withdrawing group on phosphatase activity

“…The hydrolysis of 4-NPP in the presence of zinc complexes (1-3) was run on the UV spectrophotometer following the increase in absorption at 428 nm due to the formation of 4-nitrophenolate ion (ε, 18500 M −1 cm −1 ) at 25 • C. 26 The kinetic experiments were performed both at variable substrate or complex concentration keeping the either complex or the substrate concentration constant. 26,27 The study comprised of five sets of experiments having the complex concentration as 0.05 mM and substrate as 0.5 (10 equiv. ), 0.7 (14 equiv.…”

“…The efficiency of phosphatase activity of 1-3 was studied using phosphomonoester, (4-nitrophenyl)phosphate (4-NPP). 26,27 The hydrolytic activity of complexes was determined spectrophotometrically by monitoring the formation of 4-nitrophenolate (λ max = 428 nm) through a wavelength scan from 200 to 800 nm in aqueous DMF. 26,27 The absorption profile of complex-substrate mixture at λ max = 428 nm is shown in Figure 3 for complex 1 as a representative one and those of other complexes (2 and 3) are given in Supplementary Information ( Figures S14 and S15).…”

“…15,16 Hydrolysis of phosphate esters catalyzed by metal ion is widely studied because it is involved in many biological functions like energy transduction, biosynthesis, regulation of protein and control of secondary messengers. 17,18 Various dinuclear zinc(II) complexes [19][20][21][22][23][24][25][26][27][28][29][30] have been synthesized and studied as phosphate ester models. We are actively engaged in synthesizing dinuclear zinc(II) compounds with N,N,O-donor ligands and study of their phosphatase activity.…”

“…A comparative study of these results is made with our previously (Scheme 1) reported work 30 as well as with other similarly reported systems. 20, [26][27][28]…”