Nitrosation of melatonin by nitric oxide: a computational study

Authors

  • Adrián G. Turjanski,

    1. Departamento de Química Inorgánica, Analítica y Química-Física e INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, C1428EHA;
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  • Daniel A. Sáenz,

    1. Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires, Argentina
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  • Fabio Doctorovich,

    1. Departamento de Química Inorgánica, Analítica y Química-Física e INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, C1428EHA;
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  • Darío A. Estrin,

    1. Departamento de Química Inorgánica, Analítica y Química-Física e INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, C1428EHA;
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  • Ruth E. Rosenstein

    1. Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, Buenos Aires, Argentina
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Address reprint requests to Adrián Turjanski, Departamento de Química Inorgánica, Analítica y Química-Física and INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, C1428EHA, Buenos Aires, Argentina.
E-mail: adrian@q1.fcen.uba.ar

Abstract

Melatonin is being increasingly promoted as a therapeutic agent for the treatment of jet lag and insomnia, and is an efficient free radical scavenger. We have recently characterized a product for the reaction of melatonin with nitric oxide (NO), N-nitrosomelatonin. In the present work, reaction pathways with N1, C2, C4, C6 and C7 as possible targets for its reaction with NO that yield the respective nitroso derivatives have been investigated using semiempirical AM1 computational tools, both in vacuo and aqueous solution. Specifically, two different pathways were studied: a radical mechanism involving the hydrogen atom abstraction to yield a neutral radical followed by NO addition, and an ionic mechanism involving addition of nitrosonium ion to the indolic moiety. Our results show that the indolic nitrogen is the most probable site for nitrosation by the radical mechanism, whereas different 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.

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