Oxidation of melatonin by oxoferryl hemoglobin: A mechanistic study |
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Authors: | Luisa Tesoriere Giuseppe Avellone Leopoldo Ceraulo Daniele D'Arpa Mario Allegra Maria A. Livrea |
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Affiliation: | 1. Department of Pharmaceutical Toxicological and Biological Chemistry, c/o Dipartimento di Scienze Farmacologiche, University of Palermo, Via Carlo Forlanini, 1, 90134, Palermo, Italy;2. Department of Pharmaceutical Chemistry and Technology, University of Palermo, Palermo, Italy |
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Abstract: | Reaction of melatonin with the hypervalent iron centre of oxoferryl hemoglobin, produced in aqueous solution from methemoglobin and H2O2, has been investigated at 37°C and pH 7.4, by absorption spectroscopy. The reaction results in reduction of the oxoferryl moiety with formation of a heme-ferric containing hemoprotein. Stopped-flow spectrophotometric measurements provide evidence that the reduction of oxoferryl-Hb by melatonin is first-order in oxoferryl-Hb and first-order in melatonin. The bimolecular reaction constant at pH 7.4 and 37°C is 112 ± 1.0 M-1 s-1.Two major oxidation products from melatonin have been found by gas chromatography-mass spectroscopy: the cyclic compound 1,2,3,3a,8,8a-hexahydro-1-acetyl-5-methoxy-3a-hydroxypyrrolo[2,3-b]indole (cyclic 3-hydroxy-melatonin), and N-acetyl-N′-formyl 5-methoxykynuramine (AFMK). The percentage yield of the two major products appears dependent on the ratio [oxoferryl-Hb]: [melatonin]—the higher the ratio the higher the yield of AFMK. The observed stoichiometry oxoferryl-Hbreduced:melatoninconsumed is 2, when the ratio [oxoferryl-Hb]:[melatonin] is 1:1, but appears >2 at higher molar ratios. The reduction of the hypervalent iron of the oxoferryl moiety may be consistent with an oxidation of melatonin by two one-electron steps. |
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Keywords: | Gas chromatography-mass spectroscopy Hemoglobin Melatonin Oxoferryl-Hb Melatonin oxidation H-NMR AFMK Cyclic 3-hydroxymelatonin |
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