A Heterodinuclear Fe^IIIZn^II Complex as a Mimic for Purple Acid Phosphatase with Site‐Specific Zn^II Binding

Abstract

Purple acid phosphatases (PAPs) are the only dinuclear metallohydrolases for which the necessity for a heterovalent active site (Fe III -M II ; M = Fe, Zn or Mn) for catalysis has been established. A major goal for the synthesis of PAP biomimetics is to design a ligand in which the two coordination sites exhibit discrimination between the trivalent and divalent metal ions. With this goal in mind the ligand 2-{[bis(2-methoxyethyl)amino]methyl}-6-{[(2-hydroxybenzyl)(2-pyridylmethyl)amino]methyl}-4-methylphenol (BMMHPH 2 ), with two distinct coordination sites, N 2 O 2 (α) and NO 3 (β), has been prepared. Although not exactly mimicking the active site of PAP, the ligand facilitated the formation of the complex [Fe III Zn II (BMMHP)(CH 3 COO) 2 ](BPh 4 ), which exhibited regioselectivity in the two metal binding sites. The phos-

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

“…In particular, the variation of N/O donor functionalities yielded several binucleating ligands containing {[N 3 O], [N 3 O]}, 25,30,31 {[N 3 O], [N 2 O 2 ]}, 32−42 {[N 3 O], [NO 3 ]}, 43,44 {[N 3 O], [N 2 O]}, 26 {[N 2 O 2 ], [NO 3 ]}, 24 and {[N 2 O 2 ], [N 2 O]} 45−47 donor sites that successfully stabilized a large number of hetero-dinuclear M(II)–M′(III) [M(II) = Fe(II), Mn(II), Zn(II), Cu(II), Co(II), and Ni(II) and M′(III) = Fe(III) and Ga(III)] cores mimicking the PAP enzyme active site. Of these, notable are the {[N 3 O], [N 2 O 2 ]} ligand systems containing Zn(II)–Fe(III), 18,35,39 Co(II)–Fe(III), 32,34 Cu(II)–Fe(III), 33,36 Mn(II)–Fe(III), 38 and Ni(II)–Fe(III) 37 cores and the {[N 2 O 2 ], [N 2 O]} ligand systems containing Zn(II)–Fe(III), Co(II)–Fe(III), Mn(II)–Fe(III), and Ni(II)–Fe(III) 45−47 cores that exhibited high PAP activities.…”

Synthesis, Magnetic Properties, and Catalytic Properties of a Nickel(II)-Dependent Biomimetic of Metallohydrolases

“…Thus, although no suitable nucleophile (OH − ) is present in the original molecule the replacement of the two acetate bridges by water and/or substrate molecules (Figure 8 ) may not be rate-limiting. The complex is proposed to employ a similar mechanism as proposed for a series of analogous model systems for enzymes such as PAPs (Smith et al, 2009 ; Comba et al, 2012a , b ; Bernhardt et al, 2015 ; Roberts et al, 2015 ; Bosch et al, 2016 ). The majority of complexes listed in Table 3 attain optimal catalytic efficiency under alkaline conditions (>pH 9.0), somewhat higher than the pH optimum of the di-Ni(II) enzyme urease (pH 7.4).…”

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.…”

“…The unsymmetric ligand H 2 L30 provides an N 2 O 2 and an NO 3 site. The speciation plot and rate-pH profile suggest that its Fe(III)Zn(II) complex mimics the mechanistic flexibility of PAP (Roberts et al, 2015). At a low pH, [Fe L30 (OH)(H 2 O)Zn(H 2 O)] 2+ is the active species and the terminally bound OH acts as the nucleophile.…”