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

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posted on 06.01.2014, 00:00 by Ria Sanyal, Averi Guha, Totan Ghosh, Tapan Kumar Mondal, Ennio Zangrando, Debasis Das
A mononucleating (HL1) and a dinucleating (HL2) “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 HL1 and HL2 with ZnIIX2 (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(L1)2X2] (13), while the potential dinucleating ligand generated mononuclear complexes, [Zn­(HL2)­X2] (46). Four (14), 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.