A Heterodinuclear FeIIIZnII Complex as a Mimic for Purple Acid Phosphatase with Site-Specific ZnII Binding

• Published in: European journal of inorganic chemistry Vol. 2015; no. 19; pp. 3076 - 3086
• Main Authors: Roberts, Asha E., Schenk, Gerhard, Gahan, Lawrence R.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01-07-2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Bioinorganic chemistry; Biomimetic synthesis; Enzyme models; Phospho­diester-degrading enzyme; Purple acid phosphatase
• ISSN: 1434-1948; 1099-0682
• DOI: 10.1002/ejic.201500351

Purple acid phosphatases (PAPs) are the only dinuclear metallohydrolases for which the necessity for a heterovalent active site (FeIII–MII; 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 (BMMHPH2), with two distinct coordination sites, N2O2 (α) and NO3 (β), has been prepared. Although not exactly mimicking the active site of PAP, the ligand facilitated the formation of the complex [FeIIIZnII(BMMHP)(CH3COO)2](BPh4), which exhibited regioselectivity in the two metal binding sites. The phosphoesterase‐like activity of the complex in 50:50 acetonitrile/water was investigated by using the substrate bis(2,4‐dinitrophenyl) phosphate (BDNPP) yielding kinetically relevant pKa values of 6.89, 7.37 and 9.00, a KM of 10.8 ± 2.1 mM and a kcat of 3.20 ± 0.38 × 10–3 s–1 (at pH = 7.5). Attempts to prepare a diiron analogue resulted in a centrosymmetric dimer, [FeIII2(BMMHPH)2(μ‐OH)2](BPh4)2, with one six‐coordinate FeIII atom in each of the α‐sites, connected by two μ‐hydroxido groups. In this Fe(μ‐OH)2Fe diamond core the FeIII ions are weakly antiferromagnetically coupled, with J = –1.76 ± 0.03 cm–1. The β‐sites were vacant. Attempts to replace the ZnII ion with MgII resulted in the formation of a centrosymmetric trimer, i.e. [FeIII2MgII(BMMHPH)2(CH3COO)2(CH3O)2](BPh4)2.
The ligand 2‐{[bis(2‐methoxyethyl)amino]methyl}‐6‐{[(2‐hydroxybenzyl)(2‐pyridylmethyl)amino]methyl}‐4‐methylphenol (BMMHPH2) with two distinct coordination sites, N2O2 (α) and NO3 (β), and the corresponding iron(III)–zinc(II) complex [FeZn(BMMHP)(CH3COO)2](BPh4) were prepared as a mimic for the active site of the plant enzyme purple acid phosphatase. The complex exhibits phosphoesterase‐like activity. The centrosymmetric dimer [Fe2(BMMHPH)2(μ‐OH)2](BPh4)2 and the acentrosymmetric trimer [Fe2Mg(BMMHPH)2(CH3COO)2(CH3O)2](BPh4)2 were also characterized.