Nitrosation of melatonin by nitric oxide: a computational study

Melatonin is being increasingly promoted as a therapeutic agent for the tre atment of jet lag and insomnia, and is an efficient free radical scavenger. We have recently characterized a product for the reaction of melatonin wit h nitric oxide (NO), N-nitrosomelatonin. In the present work, reaction path ways with N1, C2, C4, C6 and C7 as possible targets for its reaction with N O that yield the respective nitroso derivatives have been investigated usin g semiempirical AM1 computational tools, both in vacuo and aqueous solution . Specifically, two different pathways were studied: a radical mechanism in volving the hydrogen atom abstraction to yield a neutral radical followed b y NO addition, and an ionic mechanism involving addition of nitrosonium ion to the indolic moiety. Our results show that the indolic nitrogen is the m ost probable site for nitrosation by the radical mechanism, whereas differe nt targets are probable considering the ionic pathway. These results are in good agreement with previous experimental findings and provide a coherent picture for the interaction of melatonin with NO.