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A dinuclear zinc(II) complex of a new unsymmetric ligand with an N5O2 donor set; A structural and functional model for the active site of zinc phosphoesterases.

Das, Biswanath LU ; Daver, Henrik; Pyrkosz-Bulska, Monika; Persch, Elke; Barman, Suman K; Mukherjee, Rabindranath; Gumienna-Kontecka, Elzbieta; Jarenmark, Martin LU ; Himo, Fahmi and Nordlander, Ebbe LU (2014) In Journal of Inorganic Biochemistry 132(Online 13 August 2013). p.6-17
Abstract
The dinuclear complex [Zn2(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, [Zn2(DPCPMP)](2+) and... (More)
The dinuclear complex [Zn2(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, [Zn2(DPCPMP)](2+) and [Zn2(DPCPMP)(OH)](+) predominate the solution above pH4. The relatively high pKa 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(‡)=108.0kJmol(-1). The cumulative results indicate the hydroxido-bridged dinuclear Zn(II) complex [Zn2(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 (SN2 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. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Inorganic Biochemistry
volume
132
issue
Online 13 August 2013
pages
6 - 17
publisher
Elsevier
external identifiers
  • pmid:24001510
  • wos:000333443800003
  • scopus:84896713681
ISSN
1873-3344
DOI
10.1016/j.jinorgbio.2013.08.001
language
English
LU publication?
yes
id
ebed4939-d6f0-4788-95fa-0557b8c655a6 (old id 4066314)
date added to LUP
2013-11-14 11:44:05
date last changed
2017-07-02 03:25:32
@article{ebed4939-d6f0-4788-95fa-0557b8c655a6,
  abstract     = {The dinuclear complex [Zn2(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, [Zn2(DPCPMP)](2+) and [Zn2(DPCPMP)(OH)](+) predominate the solution above pH4. The relatively high pKa 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(‡)=108.0kJmol(-1). The cumulative results indicate the hydroxido-bridged dinuclear Zn(II) complex [Zn2(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 (SN2 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.},
  author       = {Das, Biswanath and Daver, Henrik and Pyrkosz-Bulska, Monika and Persch, Elke and Barman, Suman K and Mukherjee, Rabindranath and Gumienna-Kontecka, Elzbieta and Jarenmark, Martin and Himo, Fahmi and Nordlander, Ebbe},
  issn         = {1873-3344},
  language     = {eng},
  number       = {Online 13 August 2013},
  pages        = {6--17},
  publisher    = {Elsevier},
  series       = {Journal of Inorganic Biochemistry},
  title        = {A dinuclear zinc(II) complex of a new unsymmetric ligand with an N5O2 donor set; A structural and functional model for the active site of zinc phosphoesterases.},
  url          = {http://dx.doi.org/10.1016/j.jinorgbio.2013.08.001},
  volume       = {132},
  year         = {2014},
}