Influence of the Coordination Environment of Zinc(II) Complexes of Designed Mannich Ligands on Phosphatase Activity: A Combined Experimental and Theoretical Study
| Autor: | Totan Ghosh, Tapan Kumar Mondal, Debasis Das, Averi Guha, Ennio Zangrando, Ria Sanyal |
|---|---|
| Přispěvatelé: | Sanyal, Ria, Guha, Averi, Ghosh, Totan, Mondal, Tapan Kumar, Zangrando, Ennio, Das, Debasis |
| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Stereochemistry chemistry.chemical_element Ligand Zinc Phosphoric Monoester Hydrolase Ligands Medicinal chemistry Inorganic Chemistry chemistry.chemical_compound Models Coordination Complexes Combinatorial Chemistry Techniques Molecule Physical and Theoretical Chemistry Solubility Mannich reaction Combinatorial Chemistry Technique Kinetic Coordination Complexe Molecular Structure Chemistry Hydrolysis Enzyme Activation Kinetics Phosphoric Monoester Hydrolases Quantum Theory Molecular Hydrolysi Trigonal bipyramidal molecular geometry Dimethylformamide Amine gas treating |
| Zdroj: | Inorganic Chemistry. 53:85-96 |
| ISSN: | 1520-510X 0020-1669 |
| DOI: | 10.1021/ic4015493 |
| Popis: | 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 123456, 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|