TY - JOUR

T1 - An Unsymmetric Ligand with a N5O2 Donor Set and Its Corresponding Dizinc Complex

T2 - A Structural and Functional Phosphoesterase Model

AU - Das, Biswanath

AU - Daver, Henrik

AU - Pyrkosz-Bulska, Monika

AU - Gumienna-Kontecka, Elzbieta

AU - Himo, Fahmi

AU - Nordlander, Ebbe

PY - 2018/9/30

Y1 - 2018/9/30

N2 - To mimic the active sites of the hydrolytic enzyme zinc phosphotriesterase, a new dinucleating unsymmetric ligand, PICIMP (2-{[2-hydroxy-5-methyl-3-({[(1-methyl-1H-imidazol-2-yl)methyl](pyridin-2-ylmethyl)amino}methyl)benzyl][(1-methyl-1H-imidazol-2-yl)methyl]amino}acetic acid), has been synthesized and characterized. The hydrolytic efficacy of the complex solution (PICIMP/ZnCl2 = 1:2) has been investigated using bis-(2,4-dinitrophenyl)phosphate (BDNPP), a DNA analogue substrate. Speciation studies were undertaken by potentiometric titrations at varying pH for both the ligand and the corresponding dizinc complex to elucidate the formation of the active hydrolysis catalyst; these studies reveal that the dinuclear zinc(II) complexes, [Zn2(PICIMP)]2+ and [Zn2(PICIMP)(OH)]+ predominate in solution above pH 4. The obtained pKa of 7.44 for the deprotonation of water suggests formation of a bridging hydroxide between the two ZnII ions. Kinetic investigations of BDNPP hydrolysis over the pH range 5.5–10.5 have been performed. The cumulative results indicate the hydroxo-bridged dinuclear ZnII complex [Zn2(PICIMP)(µ-OH)]+ as the effective catalyst. Density functional theory calculations were performed to investigate the detailed reaction mechanism. The calculations suggest that the bridging hydroxide becomes terminally coordinated to one of the zinc ions before performing the nucleophilic attack in the reaction.

AB - To mimic the active sites of the hydrolytic enzyme zinc phosphotriesterase, a new dinucleating unsymmetric ligand, PICIMP (2-{[2-hydroxy-5-methyl-3-({[(1-methyl-1H-imidazol-2-yl)methyl](pyridin-2-ylmethyl)amino}methyl)benzyl][(1-methyl-1H-imidazol-2-yl)methyl]amino}acetic acid), has been synthesized and characterized. The hydrolytic efficacy of the complex solution (PICIMP/ZnCl2 = 1:2) has been investigated using bis-(2,4-dinitrophenyl)phosphate (BDNPP), a DNA analogue substrate. Speciation studies were undertaken by potentiometric titrations at varying pH for both the ligand and the corresponding dizinc complex to elucidate the formation of the active hydrolysis catalyst; these studies reveal that the dinuclear zinc(II) complexes, [Zn2(PICIMP)]2+ and [Zn2(PICIMP)(OH)]+ predominate in solution above pH 4. The obtained pKa of 7.44 for the deprotonation of water suggests formation of a bridging hydroxide between the two ZnII ions. Kinetic investigations of BDNPP hydrolysis over the pH range 5.5–10.5 have been performed. The cumulative results indicate the hydroxo-bridged dinuclear ZnII complex [Zn2(PICIMP)(µ-OH)]+ as the effective catalyst. Density functional theory calculations were performed to investigate the detailed reaction mechanism. The calculations suggest that the bridging hydroxide becomes terminally coordinated to one of the zinc ions before performing the nucleophilic attack in the reaction.

KW - Active sites

KW - Coordination chemistry

KW - Metalloenzymes

KW - Phosphoester hydrolysis

UR - http://www.scopus.com/inward/record.url?scp=85047737484&partnerID=8YFLogxK

U2 - 10.1002/ejic.201701416

DO - 10.1002/ejic.201701416

M3 - Journal article

AN - SCOPUS:85047737484

VL - 2018

SP - 4004

EP - 4013

JO - European Journal of Inorganic Chemistry

JF - European Journal of Inorganic Chemistry

SN - 1434-1948

IS - 36

ER -