TY - JOUR

T1 - A dinuclear zinc(II) complex of a new unsymmetric ligand with an N 5O2 donor set; A structural and functional model for the active site of zinc phosphoesterases

AU - Das, Biswanath

AU - Daver, Henrik

AU - Pyrkosz-Bulska, Monika

AU - Persch, Elke

AU - Barman, Suman K.

AU - Mukherjee, Rabindranath

AU - Gumienna-Kontecka, Elzbieta

AU - Jarenmark, Martin

AU - Himo, Fahmi

AU - Nordlander, Ebbe

PY - 2014/3

Y1 - 2014/3

N2 - 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 pH 4. 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‡ = 95.6 kJ mol- 1, ΔS‡ = - 44.8 J mol- 1 K- 1, and ΔG‡ = 108.0 kJ mol- 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 (S N2 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.

AB - 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 pH 4. 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‡ = 95.6 kJ mol- 1, ΔS‡ = - 44.8 J mol- 1 K- 1, and ΔG‡ = 108.0 kJ mol- 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 (S N2 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.

KW - Dinuclear active sites

KW - DNA analog

KW - Transition state

KW - Zinc phosphoesterases

UR - http://www.scopus.com/inward/record.url?scp=84896713681&partnerID=8YFLogxK

U2 - 10.1016/j.jinorgbio.2013.08.001

DO - 10.1016/j.jinorgbio.2013.08.001

M3 - Journal article

C2 - 24001510

AN - SCOPUS:84896713681

VL - 132

SP - 6

EP - 17

JO - Journal of Inorganic Biochemistry

JF - Journal of Inorganic Biochemistry

SN - 0162-0134

IS - 1

ER -