Diversion of the melanin synthetic pathway by dopamine product scavengers: A quantum chemical modeling of the reaction mechanisms

Abstract

ABSTRACT. We report the stability and reactivity of the oxidation products as well as L-cysteine and Nacetylcysteine adducts of dopamine studied using quantum chemical calculations. The overall reactions studied were subdivided into four reaction channels. The first reaction channel is the oxidation of dopamine to form dopaminoquinone. The second reaction channel leads to melanin formation through subsequent reactions. The third and fourth reaction channels are reactions leading to the formation of dopaminoquinone adducts which are aimed to divert the synthesis of melanin. The results indicate that L-cysteine and N-acetylcysteine undergo chemical reactions mainly at C5 position of dopaminoquinone. The analyses of the thermodynamic energies indicate that L-cysteine and N-acetylcysteine covalently bind to dopaminoquinone by competing with the internal cyclization reaction of dopaminoquinone which leads to the synthesis of melanin. The analysis of the results, based on the reaction free energies, is also supported by the investigation of the natural bond orbitals of the reactants and products.

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“…This type of structure has been studied in previous works. 40,41 Geometry optimizations and frequency calculations of the open arrays, as well as the five lower energy arrangement found by the conformation analysis, were performed at the B3LYP-D3(BJ)/def2-TZVP level of theory with the Gaussian 16 program. 42…”

“…This type of structure has been studied in previous works. 40,41 Geometry optimizations and frequency calculations of the open arrays, as well as the five lower energy arrangement found by the conformation analysis, were performed at the B3LYP-D3(BJ)/def2-TZVP level of theory with the Gaussian 16 program. 42 Geometry optimizations and vibrational analysis of CDA with diatomic AgNPs were carried out, with the same level of theory, to explore the possible interaction sites.…”