Autoxidation of melatonin at excited state: mechanism proposal for formation of N1-acetyl-N2-formyl-5-methoxykynuramine

Abstract

N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) is one of the primary oxidation products of melatonin. There is growing evidence of its beneficial biological properties, including antioxidant features and modulators of cytokines and enzymes involved in the inflammatory process. Here, the autoxidation of melatonin mediated by UVC was studied regarding the formation of AFMK and the reaction mechanism. The parameters evaluated were irradiation, pH, dissolved oxygen, superoxide radical anion, and hydroxyl radical. We found that the AFMK yield is directly correlated with UVC irradiation. The AFMK concentration decreased 95% when a 280 nm cutoff filter blocked the irradiation. By removing the dissolved oxygen from the medium, the decrease was 90%. Superoxide dismutase, acting as a scavenger of superoxide radical anion, caused a 64% reduction. At pH 7.0, the AFMK yield was just 14% of those obtained at pH 10. These findings are consistent with a typical autoxidation reaction. In addition, the low yield of AFMK in the absence of UVC irradiation suggested that electronically excited melatonin is the species involved in the initial electron transfer. Density Functional Theory (DFT) calculations were performed to strengthen the proposal. Corroborant with the experimental results, the theoretical analyses revealed that electron transfer from melatonin to molecular oxygen is only energetically feasible in the excited state. In conclusion, the direct autoxidation of melatonin at excited state in alkaline pH is a straightforward approach to producing AFMK.