Pulse radiolysis studies of melatonin and chloromelatonin

The endogenous indole melatonin and the melatonin receptor agonist 6-chloromelatonin block the proliferation of both dermal and uveal melanoma cells by mechanisms that may involve redox reactions. The interactions of hydrated electrons, the azide radical, hydroxyl radicals and superoxide with melatonin and its 6-chloro analogue have been studied using the technique of pulse radiolysis. The reaction rate constants of e(aq)(-) and N-3 . with these compounds were found to be dependent on substitution at the sixth position. The rate constants for reaction of 6-chloromelatonin and melatonin with solvated electrons are 4.5 x 10(9) M-1 s(-1) and 4.2 x 108 M-1 s(-1), respectively. The reaction rate constants of N-3 . with melatonin and chloromelatonin are 9.8 x 10(9) M-1 s(-1) and 3.5 x 10(9) M-1 s(-1), respectively. Melatonin and 6-chloromelatonin react with hydroxyl radicals at near diffusion controlled rates (1.3 x 10(10) M-1 s(-1), 8.2 x 10(9) M-1 s(-1)). Melatonin and 6-chloromelatonin did not react with superoxide radicals and we calculate an upper limit of 1.0 x 10(4) M-1 s(-1) for the rate constant for reaction of melatonin and 6-chloromelatonin with superoxide ion. (C) 1998 Elsevier Science S.A.