title: A dinuclear zinc(II) complex of a new unsymmetric ligand with an N(5)O(2) donor set: a structural and functional model for the active site of zinc phosphoesterases.
abstract: The dinuclear complex [Zn(2)(DPCPMP)(pivalate)](ClO4), where DPCPMP is the new unsymmetrical ligand [2-(N-(3-((bis((pyridin-2-yl)methyl)amino)methyl)-2-hydroxy-5-methylbenzyl)-N-((pyridin-2-yl)methyl)amino)acetic acid], has been synthesized and characterized. The complex is a functional model for zinc phosphoesterases with dinuclear active sites. The hydrolytic efficacy of the complex has been investigated using bis-(2,4-dinitrophenyl)phosphate (BDNPP), a DNA analog, as substrate. Speciation studies using potentiometric titrations have been performed for both the ligand and the corresponding dizinc complex to elucidate the formation of the active hydrolysis catalyst; they reveals that the dinuclear zinc(II) complexes, [Zn(2)(DPCPMP)](2+) and [Zn(2)(DPCPMP)(OH)](+) predominate the solution above pH4. The relatively high pK(a) of 8.38 for water deprotonation suggests that a terminal hydroxide complex is formed. Kinetic investigations of BDNPP hydrolysis over the pH range 5.5-11.0 and with varying metal to ligand ratio (metal salt:ligand=0.5:1 to 3:1) have been performed. Variable temperature studies gave the activation parameters ΔH(‡)=95.6kJmol(-1), ΔS(‡)=-44.8Jmol(-1)K(-1), and ΔG(‡)=108.0 kJmol(-1). The cumulative results indicate the hydroxido-bridged dinuclear Zn(II) complex [Zn(2)(DPCPMP)(μ-OH)](+) as the effective catalyst. The mechanism of hydrolysis has been probed by computational modeling using density functional theory (DFT). Calculations show that the reaction goes through one concerted step (S(N)2 type) in which the bridging hydroxide in the transition state becomes terminal and performs a nucleophilic attack on the BDNPP phosphorus; the leaving group dissociates simultaneously in an overall inner sphere type activation. The calculated free energy barrier is in good agreement with the experimentally determined activation parameters.
authors.affiliation: Inorganic Chemistry Research Group, Chemical Physics, Center for Chemistry and Chemical Engineering, Lund University, P.O. Box 124, SE-22100 Lund, Sweden.
authors.forename: Biswanath
authors.initials: B
authors.lastname: Das
authors.affiliation: Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Daver
authors.affiliation: Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie Street 14, 50-383 Wroclaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Pyrkosz-Bulska
authors.affiliation: Inorganic Chemistry Research Group, Chemical Physics, Center for Chemistry and Chemical Engineering, Lund University, P.O. Box 124, SE-22100 Lund, Sweden.
authors.forename: Elke
authors.initials: E
authors.lastname: Persch
authors.affiliation: Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208 016, India.
authors.forename: Suman K
authors.initials: SK
authors.lastname: Barman
authors.affiliation: Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208 016, India.
authors.forename: Rabindranath
authors.initials: R
authors.lastname: Mukherjee
authors.affiliation: Faculty of Chemistry, University of Wroclaw, F. Joliot-Curie Street 14, 50-383 Wroclaw, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Gumienna-Kontecka
authors.affiliation: Inorganic Chemistry Research Group, Chemical Physics, Center for Chemistry and Chemical Engineering, Lund University, P.O. Box 124, SE-22100 Lund, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Jarenmark
authors.affiliation: Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Fahmi
authors.initials: F
authors.lastname: Himo
authors.affiliation: Inorganic Chemistry Research Group, Chemical Physics, Center for Chemistry and Chemical Engineering, Lund University, P.O. Box 124, SE-22100 Lund, Sweden. Electronic address: Ebbe.Nordlander@chemphys.lu.se.
authors.forename: Ebbe
authors.initials: E
authors.lastname: Nordlander
mesh_terms: D020134:Catalytic Domain; D003198:Computer Simulation; D056831:Coordination Complexes / Q000737:chemistry*; D004950:Esterases / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009589:Nitrogen Oxides / Q000737:chemistry*; D010758:Phosphorus / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
chemical_list: D056831:Coordination Complexes; D008024:Ligands; D009589:Nitrogen Oxides; D010758:Phosphorus; C010125:nitrogen pentoxide; D004950:Esterases; D015032:Zinc
keywords: DNA analog; Dinuclear active sites; Transition state; Zinc phosphoesterases