Synthesis and characterization of Fe^III(μ-OH)Zn^II complexes: effects of a second coordination sphere and increase in the chelate ring size on the hydrolysis of a phosphate diester and DNA

Abstract

The synthesis and characterization of three ligands and their respective heterobinuclear FeZn complexes were carried out, with the goal of mimicking the active site of purple acid phosphatases (PAPs). The ligand 2-hydroxy-3-(((2-hydroxy-5-methyl-3-(((2-(pyridin-2-yl)ethyl)(pyridin-2-ylmethyl)amino)methyl)benzyl)(pyridin-2ylmethyl)amino)methyl)-5-methylbenzaldehyde (HL) was synthesized and its complex (FeZnL) was used as a basis for comparison with similar complexes previously published in the literature. Subsequent modifications were conducted in the aldehyde group, where 1,2-ethanediamine and 1,4-diaminobutane were used as side chain derivatives. The compounds FeZnL (1), FeZnL-et (2) and FeZnL-but (3) were characterized by spectroscopic methods (infrared and UV-Vis) and ESI-MS spectrometry. Theoretical calculations were performed to provide insights into the complex structures with FeZn structures. The hydrolytic activity was analyzed both with the model substrate 2,4-BDNPP and with DNA catalyzed by complexes 1, 2 and 3.

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

“…For some of the active site mimics that hydrolyzed a DNA model substrate, the DNase activity was also evaluated using plasmid DNA. While there are examples for DNA cleavage activity (Peralta et al, 2010; Anbu et al, 2012; Montagner et al, 2014; Silva et al, 2017; Camargo et al, 2018), it is apparent that factors that are not important for simple phosphodiesters affect the hydrolysis of macromolecular DNA. Binding to a phosphodiester group in DNA can be sterically hindered by a bulky organic ligand (Massoud et al, 2016).…”

“…H 2 L29 a , H 2 L29 b , and H 2 L29 c were synthesized to model secondary interactions between the phosphate ester substrate and positively charged amino acid residues in the active site of PAP (Silva et al, 2017). The presence of the side chains in H 2 L29 b and H 2 L29 c led to a decrease in the pK a value of Fe(III)-OH 2 by 0.6 and 0.8 pH units compared to the parent complex and to a shift of the redox potential of Fe(III) to less negative values.…”

Recent Advances in Heterogeneous Catalytic Systems Containing Metal Ions for Phosphate Ester Hydrolysis

“…For example, the half‐life for the hydrolysis of dimethylphosphate is estimated to be 130 000 years [15] . Approaches that use photolytic degradation by sunlight [16] and biological pathways, [17] as well as their hydrolysis by biomimetic compounds, have been employed to solve the problem of the natural persistence of such compounds [18–30] . The use of biomimetic compounds offers a number of advantages, including the possibility to immobilise these compounds on the surface of insoluble solid matrices for easier handling and reuse [31] …”

“…[15] Approaches that use photolytic degradationb ys unlight [16] and biological pathways, [17] as well as their hydrolysis by biomimetic compounds, have been employed to solve the problem of the natural persistence of such compounds. [18][19][20][21][22][23][24][25][26][27][28][29][30] The use of biomimetic compounds offers a number of advantages, including the possibility to immobilise these compounds on the surface of insoluble solid matrices for easier handling and reuse. [31] Compared with extensivelys tudied homogeneousc atalysts that hydrolyse diverse phosphoester bonds, [28,[32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] far fewer heterogeneous systemst hat catalyse the cleavage of such bonds have been developed.…”

Cu(II)‐catalyzed hydrolysis of tris‐2‐pyridyl phosphate assisted by sodium dodecyl sulfate micelles

“…The investigation of simple models of metal‐catalyzed phosphate transfer reaction has been a recurring strategy directed to understand the mechanistic roles of metal ions in biochemical transformations, occurring in high complexity enzymatic systems. Provided that water is the medium of the biological systems, and that phosphate transfer to water is actually the uncatalyzed reaction of a great variety of hydrolytic enzymes, the catalytic effect of metal complexes featuring organic ligands in the hydrolysis of phosphate esters has proven to be highly relevant to a better understanding of enzyme action …”