EDTA–Fe²⁺ Complex-Functionalized Fe₃O₄ Nanozyme as Tyrosine Hydroxylase Mimics for the Production of l-DOPA

Abstract

l-3,4-Dihydroxyphenylalanine (l-DOPA) is widely used in the treatment of Parkinson’s disease. Fe3O4 magnetic nanoparticles decorated with ethylenediaminetetraacetic acid (EDTA)–Fe2+ complexes were developed as nanozymes for the biomimetic synthesis of l-DOPA by mimicking tyrosine hydroxylase. The nanozyme was synthesized by anchoring Fe2+ ions onto EDTA-grafted Fe3O4 magnetic nanoparticles. Scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Fourier-transform infrared, X-ray photoelectron spectroscopy, Brunauer–Emmett–Teller, and vibrating-sample magnetometer characterized the nanozyme-possessed nanoscale features, high specific surface area, and good superparamagnetic properties. The nanozyme has a coordination structure comprising an EDTA–Fe2+ complex that resembles the catalytic site of tyrosine hydroxylase. The nanozyme exhibited high catalytic performance for the conversion of tyrosine to l-DOPA, with properties similar to those of tyrosine hydroxylase (K m = 8.7 mM). The yield and titer of l-DOPA were 28% and 1.7 mM, respectively. The nanozyme showed excellent reusability over five successive cycles. The data showed that hydroxyl radicals and singlet oxygen are the primary active species and the catalytic mechanism of the nanozyme is similar to that of tyrosine hydroxylase. The magnetically separable and recyclable nanozyme has potential applications in the low-cost and high-efficiency production of l-DOPA.

Polymerization of l-Tyrosine, l-Phenylalanine, and 2-Phenylethylamine as a Versatile Method of Surface Modification for Implantable Medical Devices

“…After a laborious workup, the product of hydroxylation at position C3 in the aromatic ring, i.e., levodopa, was obtained, which was proven by extracting and analyzing this product from the reaction mixture. There are also other examples of metal-catalyzed oxidation of l -tyrosine, l -phenylalanine, and 2-phenylethylamine that rationalize the hypothesis of mono- and dihydroxylation as the first initial step of the proposed polymerization. − All of these suggest, in this condition, that the hydroxylation of the aromatic ring occurs, and then the oxidative polymerization of levodopa may occur with a similar mechanism to dopamine (Scheme , R = CO 2 H). It is likely that both l -phenylalanine and 2-phenylethylamine may undergo a similar mechanism.…”

Mussel Inspired In Situ Preparation of Antibacterial Silver Nanoparticles by DOPA‐Containing Silk Fibroin

“…The results were consistent with previous researches. [ 17,18 ] HPLC, Arnow assay, NBT assay, and ethylenediamine assay indicated that a part of tyrosine residues of fibroin was successfully transformed into DOPA residues (Figure S1, Supporting Information).…”

“…In recent studies, a biomimetic synthesis method was developed to convert tyrosine to DOPA by mimicking tyrosine hydroxylase, in which complex between Fe 2+ and ethylenediaminetetraacetic acid (EDTA) performed as active site with H 2 O 2 as oxygen donor and ascorbic acid as reducing agent. [17,18] This biomimetic synthesis method had the advantages of quick reaction and environmental friendliness.…”

In situ continuous Dopa supply by responsive artificial enzyme for the treatment of Parkinson’s disease

“…Iron-based catalysts have been reported to catalyze the hydroxylation of tyrosine and achieve high catalytic conversion 24 , 25 . Based on the further investigation of nanozymes, we proved that Fe 3 O 4 could generate Fe(IV)=O active intermediates.…”