Melatonin (N-acetyl-5-methoxytryptamine, MLT), an indole hormone synthesized primarily in the pineal gland and the retina, controls several essential physiological functions associated with circadian and seasonal rhythms. It is involved in immune responses, aging processes and age-related diseases. Because all these process are associated with oxidative damage of vital cell components, it has been postulated that melatonin may function as a natural antioxidant and free radical scavenger. The primary objective of this research project was to determine rate constants for the reaction of MLT with free radicals (OH, CH3, OCH3) and with singlet oxygen (1O2). In addition to MLT, we studied related indoles 6-hydroxymelatonin, 6-chloromelatonin, 5- methoxytrypatmine, 5-hydroxytryptamine, and a tryptophan metabolite kynurenine. It was found that all the indoles react with OH at near diffusion controlled rates,[kr(indole/OH)-1010 M-1s-1, for MLT kr=2.6x1010 M-1s-1]. The interaction of the indoles with CH3 radicals is less efficient, and occurs with the rate constant of 17 M-1 s-1. In contrast, scavenging of OCH3 is a very fast process (k - 109 M-1s-1). The 1O2 quenching efficacy depends on the position and the nature of the substituent(s) of the indole nucleus, and also on the reaction environment. In CH3CN and CD3OD the 1O2 quenching occurs with the rate 107-108 M-1 s-1, while in D2O the quenching is more than ten-fold faster. Given the reported low toxicity of MLT, its ready accumulation in all types of cells due to its high lipophilicity and distribution throughout the entire body via the blood stream, melatonin may be considered as a potentially important natural antioxidant.
