Comparative Studies of Structures and Peroxidase-like Activities of Copper(II) and Iron(III) Complexes with an EDTA-Based Phenylene-Macrocycle and Its Acyclic Analogue

Abstract

With the objective of studying the conformational and macrocyclic effects of selected metal chelates on their peroxidase activities, Cu2+ and Fe3+ complexes were synthesized with a macrocyclic derivative of ethylenediaminetetraacetic acid and o-phenylenediamine (abbreviated as edtaodH2) and its new open-chain analogue (edtabzH2). The Fe3+ complex of edtaodH2 has a peroxidase-like activity, whereas the complex of edtabzH2 does not. The X-ray study of the former shows the formation of a dimeric molecule {[Fe(edtaod)]2O} in which each metal with an octahedral coordination is overposed over the macrocyclic cavity, as a result of rigid macrocyclic frame, to form an Fe–O–Fe bridge; the exposure of the central metal to the environment facilitates the capture of oxygen to drive the biomimetic activity. The peroxidase-inactive Fe3+ complex consists of a mononuclear complex ion [Fe(edtabz)(H2O)]+, the metal ion of which is suited in a distorted pentagonal bipyramid to be protected from environmental oxygen. The copper(II) complexes, which have mononuclear structures with high thermodynamic stability compared with the iron(III) complexes, show no peroxidase activity. The steric effects play a fundamental role in the biomimetic activity.

Synthesis and characterization of bismuth(III) complex with an EDTA-based phenylene ligand and its potential as anti-virulence agent

“…The edtabz ligand was synthesized as previously described by Beltran-Torres et al (2019). Specifically, 2.4 g (9.3 mmol) of EDTA dianhydride dissolved in 8 mL of dry dimethylformamide (DMF) was added to 2 mL (20 mmol) of aniline previously distilled.…”

“…The bismuth complex was characterized in terms of 1 H and 13 C NMR, UV-Vis, Fourier-transform infrared (FTIR), mass spectra of electrospray ionization (ESI/MS) and thermogravimetric analysis (TGA) (Beltran-Torres et al, 2019). The 1 H and 13 C NMR spectra were obtained with a Bruker AVANCE 400 spectrometer for D 2 O solutions at 25 C. The internal reference was sodium 2,2-dimethyl-2-silanpentane-5-sulfonate (DSS).…”

“…EDTA-based ligands have donor atoms that can coordinate with bismuth. It is well known that increasing the number of donor atoms of the ligands and the number of chelating rings usually results in higher stability of the complexes (Beltran-Torres et al, 2019). Nevertheless, this is not only the factor that regulates the metal coordination; other factors such as the preorganization, the charge of the ligand, the steric efficiency in which the ligand surrounds the Bi(III) ion to form a cage-like structure also play an important role (Stavila et al, 2006).…”

Bioorthogonal Catalysis for Treatment of Solid Tumors Using Thermostable, Self-Assembling, Single Enzyme Nanoparticles and Natural Product Conversion with Indole-3-acetic Acid

“…Iron has well-known biocompatibility and is present in both endogenous and exogenous enzymes with highly specific substrate specificities. 4 Peroxidase enzymes like horseradish peroxidase (HRP) have several features suitable for BC, including the ability to align the π-orbital of elemental iron with paired substrates using a heme prosthetic group. 5 Although peroxidases have been extensively studied in vitro , their use in BC for treating solid tumors has been limited due to issues of cellular delivery and in vivo protein stability.…”

“…Iron is one of the best studied transition metals and can adopt multiple oxidation states with iron­(II) and iron­(III), the ferrous and ferric forms being the most common. Iron has well-known biocompatibility and is present in both endogenous and exogenous enzymes with highly specific substrate specificities . Peroxidase enzymes like horseradish peroxidase (HRP) have several features suitable for BC, including the ability to align the π-orbital of elemental iron with paired substrates using a heme prosthetic group .…”