Tyrosinase is a copper-containing oxidase that oxidizes phenols into quinones. In the neurodegeneration of dopaminergic systems, tyrosinase enzyme oxidizes dopamine into dopamine o-quinone. Dopamine o-quinone cyclized at physiological pH to leucoaminochrome that auto oxidizes to aminochrome. Excess of reactive oxygen species like aminochrome increases the level of oxidative stress, which is considered a major contributor to a variety of neurodegenerative diseases such as Parkinson’s.<br/>To investigate the subsequent steps of dopamine oxidation in a controlled way, we aimed to find a copper-small molecule that can act effectively as tyrosinase mimic and oxidize dopamine to different quinone forms. Taking advantage of the resin beads as solid support to allow proximity of multiple copper centers and therefore allow its function as an enzyme mimic, we approached the synthesis of the copper complex on resin. In this research, we explore various organic syntheses to develop multiple copper (I) complexes and examine the oxidation of 2,4-Di-tert-butylphenol (DTBP) substrate to quinone by different copper (I) complexes on resin. The products formed under different oxidation conditions and different solvents are analyzed by Infrared spectroscopy, Liquid chromatography-mass spectrometry, and Nuclear Magnetic Resonance. The quinone product will be conjugated with a thiol group of cysteine on peptides/ proteins, to explore this chemistry in the development of quinone-containing peptides and proteins.

Optimizing and characterizing the synthesis of copper (I) complexes on resin as tyrosinase mimics

ACS Spring 2022

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