Influence of the Coordination Environment of Zinc(II) Complexes of Designed Mannich Ligands on Phosphatase Activity: A Combined Experimental and Theoretical Study

Abstract

A mononucleating (HL(1)) and a dinucleating (HL(2)) "end-off" compartmental ligand have been designed and synthesized by controlled Mannich reaction using p-cresol and bis(2-methoxyethyl)amine, and their formation has been rationalized. Six complexes have been prepared on treating HL(1) and HL(2) with Zn(II)X2 (X = Cl(-), Br(-), I(-)) with the aim to investigate their hydrolytic activity on phosphoester bond cleavage. Interestingly, the mononucleating ligand was observed to yield dinuclear complexes, [Zn2(L(1))2X2] (1-3), while the potential dinucleating ligand generated mononuclear complexes, [Zn(HL(2))X2] (4-6). Four (1-4), out of six complexes studied, were characterized by single-crystal X-ray diffraction (XRD): the Zn ion exhibits trigonal bipyramidal and tetrahedral coordination spheres in the di- and mononuclear complex, respectively. The hydrolytic kinetics, followed spectrophotometrically with 4-nitrophenylphosphate (4-NPP) in buffered dimethylformamide (DMF) (97.5% DMF, v/v) because of solubility reasons, under excess substrate conditions (substrate:complex = 20:1), indicated that the complexes enormously accelerate the rate of phosphomonoester hydrolysis with first order rate constants (kcat) in the range 2-10 s(-1) at 25 °C. In each case kinetic data analyses have been run by Michaelis-Menten treatment. The efficacy in the order of conversion of substrate to product (p-nitrophenolate ion) follows the trend 1 > 2 > 3 > 4 > 5 > 6, and the ratio of kcat of an analogous dinuclear to mononuclear complex is ≃2. An electrospray ionization-mass spectrometry (ESI-MS) study has revealed the dissociation of the centrosymmetric dinuclear complex to two mononuclear species instead of a syn-cooperative catalysis. Density functional theory (DFT) calculations have been performed to rationalize our proposed mechanistic pathway for phosphatase activity. The comparative analysis concludes the following facts under experimental conditions: (1) the halide bound to the active site affects the overall rate in the order: Cl(-) > Br(-) > I(-) regardless of nuclearity; (2) dinuclear complexes prevail over the mononuclear ones.

Crystal structure of aqua(perchlorato)bis[μ-(E)-2-({[2-(pyridin-2-yl)ethyl]imino}methyl)phenolato-κ4N,N′,O:O]dicopper(II) perchlorate

“…Compounds of transition metal complexes comprising the ({[2-(pyridin-2-yl)ethyl]imino}methyl)phenol ligand have been synthesized for various processes (Egekenze et al, 2017;Sanyal et al, 2014;Chakraborty et al, 2013;Tandon et al, 1994Tandon et al, , 2000Latour et al, 1989). Complexes of the tridentate ligand have been used as biomimics in the catalysis of hydrolysis of phosphate esters and as catalysts for catechol oxidation (Egekenze et al, 2017).…”

Catechol Oxidase, Phosphatase-Like Activity, DNA/BSA Binding Studies of RuII Complexes of S-Allyldithiocarbazate: Synthesis and Spectral Studies

“…The catalytic behavior showed saturation kinetics and a treatment based on MichaelisMenten model seemed to be appropriate under excess substrate conditions. 58 The observed rate constants (K i ) were extracted by initial rate method. Plots of the MichaelisMenten constant (K m ) and maximum initial rate (V max ) were determined by linearization using Lineweaver-Burk plots ( Figure 6).…”

Phosphatase models: Synthesis, structure and catalytic activity of zinc complexes derived from a phenolic Mannich-base ligand

“…The ''end-off'' compartmental ligands used in this work are pure Mannich-type bases and have been synthesised almost by the same procedure as described in our previous work [30], which reports the first observations on anomalous Mannich ligand reaction. The precursors p-chlorophenol, bis(2-methoxyethyl)amine and formalin were mixed together under appropriate conditions and refluxed for a prolonged period of time.…”

“…This is undeniably an anomalous observation since HL1 is an ideal ligand for the synthesis of mononuclear metallocomplexes and at the same time HL2 is a conventional dinucleating ligand [35][36][37][38][39][40]. Thus it would not be an overestimation to remark that these kind of Mannich-base compartmental ligand system will generate reverse nuclearity pattern with zinc-halides [30]. Unfortunately, complex 1 and 6 could not be structurally established by repeated endeavours.…”

“…Recently we have reported that mono-and dinuclear Zn(II) complexes derived from two novel synthesised Mannich-base ligands are not only capable of promoting the hydrolysis of activated phosphate monoesters, but likewise were found to possess promising catalytic activity [30]. In this context, here we report the synthesis and characterisation of a series of similar methoxyamine based mono-and dinuclear Zn II complexes, where the ligands differ from those previously reported for the presence in para position of the phenol ring of a chloro instead of a methyl group (Scheme 2).…”