title: 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.
authors.affiliation: Department of Chemistry, University of Calcutta , 92, A. P. C. Road, Kolkata 700009, India.
authors.forename: Ria
authors.initials: R
authors.lastname: Sanyal
authors.forename: Averi
authors.initials: A
authors.lastname: Guha
authors.forename: Totan
authors.initials: T
authors.lastname: Ghosh
authors.forename: Tapan Kumar
authors.initials: TK
authors.lastname: Mondal
authors.forename: Ennio
authors.initials: E
authors.lastname: Zangrando
authors.forename: Debasis
authors.initials: D
authors.lastname: Das
mesh_terms: D020650:Combinatorial Chemistry Techniques; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D004789:Enzyme Activation; D006868:Hydrolysis; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D011789:Quantum Theory; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism
chemical_list: D056831:Coordination Complexes; D008024:Ligands; D010744:Phosphoric Monoester Hydrolases; D015032:Zinc