Modeling the Active Site of the Purple Acid Phosphatase Enzyme with Hetero-Dinuclear Mixed Valence M(II)–Fe(III) [M = Zn, Ni, Co, and Cu] Complexes Supported over a [N₆O] Unsymmetrical Ligand

Abstract

The active site of the purple acid phosphatase enzyme has been successfully modeled by a series of hetero-dinuclear M(II)–Fe(III) [M = Zn, Ni, Co, and Cu] type complexes of an unsymmetrical [N 6 O] ligand that contained a bridging phenoxide moiety and one imidazoyl and three pyridyl moieties as the terminal N-binding sites. In particular, the hetero-dinuclear complexes, {L[M II (μ-OAc) 2 Fe III ]}(ClO 4 ) 2 [M = Zn ( 3a ), Ni ( 3b ), Co ( 4a ), and Cu ( 4b )], were obtained directly from the phenoxy-bridged ligand (HL), namely 2-{[bis(2-methylpyridyl)amino]methyl}-6-{[((1-methylimidazol-2-yl)methyl)(2-pyridylmethyl)amino]methyl}-4- t -butylphenol ( 2 ), upon sequential addition of Fe(ClO 4 ) 3 · X H 2 O and M(ClO 4 ) 2 ·6H 2 O (M = Zn and Ni) or M(OAc) 2 · X H 2 O (M = Co and Cu), in a low-to-moderate (ca. 32–53%) yield. The temperature-dependent magnetic susceptibility measurements indicated weak antiferromagnetic coupling interactions occurring between the two metal centers in their high-spin states. All of the 3 ( a–b ) and 4 ( a–b ) complexes successfully carried out the hydrolysis of the bis(2,4-dinitrophenyl)phosphate (2,4-BDNPP) substrate in a mixed CH 3 CN/H 2 O (v/v 1:1) medium in the pH range of 5.5–10.5 at room temperature, thereby mimicking the functional activity of the native enzyme. The spectrophotometric titration suggested a monoaquated and dihydroxo species of the type {L[(H 2 O)M II (μ-OH)Fe III (OH)]} 2+ to be the catalytically active species for the phosphodiester hydrolysis reaction within the pH range of ca. 5.80–7.15. Last, the kinetic studies on the hydrolysis of the model substrate, 2,4-BDNPP, divulge a Michaelis–Menten-type behavior for all complexes.

Heterodinuclear Zn(II)−Fe(III) and Homodinuclear M(II)−M(II) [M = Zn and Ni] complexes of a Bicompartmental [N 6 O] ligand as synthetic mimics of the hydrolase family of enzymes

“…Geometric parameters of the in the hetero-and homodinuclear complexes (2)(3)(4). complexes which also showed a rate maxima at pH 6.5 [69,94] and also to that of the PAP enzyme that showed a rate maxima at pH 4.9 [114]. Sigmoidal fit to the decline part of the pH profile curve gave a pK a value of 8.28 closer to the pK a3 value of 6.97 as obtained from the spectrophotometric titration studies.…”

Mechanistic Studies of Homo- and Heterodinuclear Zinc Phosphoesterase Mimics: What Has Been Learned?

“…While in the majority of the Fe(III)Zn(II) complexes of HL26 – H 2 L31 the metals are bridged by two acetates in the solid state, in solution dissociation of the acetate ligands leads to [(H 2 O)Fe L (μ-OH 2 )Zn(H 2 O)] n+ , [(H 2 O)Fe L (μ-OH)Zn(H 2 O)] (n−1)+ , [(OH)Fe L (μ-OH)Zn(H 2 O)] (n−2)+ , and [(OH)Fe L (μ-OH)Zn(OH)] (n−3)+ species, depending on the pH value (Lanznaster et al, 2002; Neves et al, 2007; Peralta et al, 2010; Piovezan et al, 2010; Jarenmark et al, 2011; Roberts et al, 2015; Pathak et al, 2017). Rate-pH profiles and potentiometric titration data indicate that [(OH)Fe L (μ-OH)Zn(H 2 O)] n+ , which is present in weakly acidic solution is the catalytically active species.…”

Synthesis, Characterization, and Reactivity of a Series of Homo‐ and Hetero‐dinuclear Complexes based on an Asymmetric FloH Ligand System

“…[22] Copper(II) was introduced in the next step. This stepwise metalation strategy that makes use of the different thermodynamic stabilities of the six-vs. five-membered chelate rings has now been extended in the present study for the preparation of a series of heterodinuclear Fe III M II [M = Mn (2), Fe (3), Co (4), and Ni (5)] and Fe II Cu I (1a), as well as homodinuclear Cu I Cu I (6) complexes (Scheme 1). The abilities of the complexes to activate dioxygen and hydrogen peroxide have been investigated; a comparative reactivity study establishes some important differences in the oxidation mechanism depending on the nature and the oxidation state of the metal ions.…”

“…These heterodinuclear active sites can exhibit alternative reactivity patterns relative to their symmetric counterparts. Hence, the synthesis and the understanding of the reactivity properties of heterodimetallic complexes are important in the context of modelling the structures and reactivities of metalloenzymes containing two different metal ions at their active sites . However, such studies are not trivial due to the challenges associated with synthesis of heterodinuclear complexes, mainly because of the possibility of disproportionation and the formation of mixtures of homo‐ and heterodinuclear complexes, as well as metal‐site isomers.…”

“…Hence, the synthesis and the understanding of the reactivity properties of heterodimetallic complexes are important in the context of modelling the structures and reactivities of metalloenzymes containing two different metal ions at their active sites. [1][2][3][4][5][6][7][8][9][10] However, such studies are not trivial due to the challenges associated with synthesis of heterodinuclear complexes, mainly because of the possibility of disproportionation and the formation of mixtures of homoand heterodinuclear complexes, as well as metal-site isomers. A limited number of successful synthesis of heterodinuclear complexes involve the use of asymmetric ligands that bind metals selectively in one pocket or strongly enough to prevent disproportionation and metal mixing.…”