Hemin‐Graphene Derivatives with Increased Peroxidase Activities Restrain Protein Tyrosine Nitration

Abstract

Protein tyrosine nitration is implicated in the occurrence and progression of pathological conditions involving free radical reactions. It is well recognized that hemin can catalyze protein tyrosine nitration in the presence of nitrite and hydrogen peroxide. Generally, the catalytic efficiency is positively correlated to its peroxidase activity. In this study, however, it is found that the efficiency of hemin in catalyzing protein tyrosine nitration is largely suppressed after functionalization with graphene derivatives, even though its peroxidase-like activity is more than quadrupled. Further studies show that the oxidation of tyrosine is still observed for these composites; dityrosine formation, however, is greatly inhibited. Furthermore, these composites also exhibit strong effects on the oxidation of nitrite into nitrate. Therefore, we propose a mechanism in which hemin-graphene derivatives facilitate the oxidation of tyrosine and nitrite to produce tyrosyl radicals and nitrogen dioxide radicals in the presence of hydrogen peroxide, but graphene interlayers serve as barriers that hinder radical-radical coupling reactions; consequently, protein tyrosine nitration is restrained. This property of hemin-graphene derivatives, by which they catalyze substrate oxidation but suppress radical-radical coupling reactions, shows their great potential in selective oxidation procedures for byproduct removal.

Insights into G-Quadruplex–Hemin Dynamics Using Atomistic Simulations: Implications for Reactivity and Folding

“…Alternatively, the mere interaction of hemin with the electron-rich aromatic surface of the G-quartet could somehow enhance the reactivity per se . For example, hemin can bind to graphene, and the complex was reported to enhance the peroxidase reaction about 100 times. , Hemin bound to graphene oxide affects the peroxidation rate, too, either slightly increasing (up to about four times) or decreasing it, depending on the experimental conditions and the degree of oxidation of graphene. − Given the similarity of the graphene (oxide) surface and a G-quartet surface, both peroxidase reactions could be enhanced by the electron-rich aromatic system. Such a model is not fully in line with the existence of a hexacoordinate iron (provided the EPR spectra reflect the actual reactive geometry) but could be rationalized by the concomitant stacking of hemin atop the quartet and coordination of iron by the four proximal carbonyl oxygens, which could act as the sixth ligand.…”

Insights into G-Quadruplex–Hemin Dynamics Using Atomistic Simulations: Implications for Reactivity and Folding

“…[88][89] Hemin bound to graphene oxide affects the peroxidation rate, too; either slightly increasing (up to about four times) or decreasing it, depending on the experimental conditions and the degree of oxidation of graphene. [90][91][92] Given the similarity of graphene (oxide) surface and a G-quartet surface, both peroxidase reactions could be enhanced by the electron-rich aromatic system. Such a model is not fully in line with the existence of a hexa-coordinate iron (provided the EPR spectra reflect the actual reactive geometry) but could be rationalized by the concomitant stacking of hemin atop the quartet and coordination of iron by the four proximal carbonyl oxygens, which could act as the sixth ligand.…”

Water-soluble Hemin-mPEG-enhanced Luminol Chemiluminescence for Sensitive Detection of Hydrogen Peroxide and Glucose

“…11 Hemin is a complex of porphyrin and ferric iron, and has a catalytic center structure similar to cytochrome, peroxidase, myohemoglobin and hemoglobin. [12][13][14] Hemin has been widely used as a peroxidase enzyme for catalytic oxidation. 15 However, there are relatively limited applications in all fields because hemin is prone to self-polymerize in the catalytic oxidation process, and has poor solubility in both organic and aqueous solvents.…”