Cyclic bond formation of rhododendrol-quinone and dopamine-quinone: Effects of proton rearrangement

The synthesis of melanin pigment involves intramolecular cyclic bond formation between benzene ring and side chain moieties of o-quinone as a necessary process for o-quinone conversion into a cyclic catechol, i.e., cyclization. Dopamine (DA)-quinone and rhododendrol (RD)-quinone undergo cyclic C–N and C–O bond formation, respectively. A previous theoretical study revealed that RD-quinone requires hydroxy deprotonation or quinonic protonation for cyclic C–O bond formation. In this study, the theoretical model was extended to an (H₂O)_n-quinone interacting system (n ¼ 3; 4) so that protonation and deprotonation governed by H₂O molecules are incorporated. Density functional theory (DFT)-based simulation showed that RD-quinone can undergo proton-rearrangement-assisted cyclic C–O bond formation with a moderate barrier height which is still higher than that for DA-quinone cyclic bond formation. The DFT-based simulation also showed that both DA-quinone and RD-quinone can undergo proton-rearrangement-assisted C–O bond formation for the addition of water with slightly higher activation energies than those of cyclic bond formation. The obtained mechanism is markedly different from that for DA-quinone, which can sequentially undergo the cyclic C–N bond formation and proton rearrangement.