Computational Quantum Chemistry Studies of Proposed Reaction Mechanisms for Direct Oxidation of Melatonin

Free radicals are connected to oxidative stress that results in aging, cancer, Parkinson's, Alzheimer's, and Sickle Cell Disease, among many other health problems. Indirect methods, such as spin trapping, are commonly used to circumvent the difficulty of direct exptl. observation and identification of short-lived free radicals. Spin trapping stabilizes and lengthens the lifetime of the radical through reaction with another mol. so that it is detectable by ESR spectroscopy. Recent efforts have been directed towards in vivo spin trapping. However, the most common nitroso and nitrone spin traps are known to be toxic at high concns. Further complicating the interpretation of the exptl. results to establish the reaction mechanisms is that the superoxide adduct of the spin trap enzymically degrades and decays into that of the hydroxyl adduct. Melatonin is a relatively nontoxic natural antioxidant that is directly reactive towards the hydroxyl radical and relatively unreactive towards the superoxide radical. While melatonin as an antioxidant has been exptl. well studied, its reaction mechanisms are still not well understood. This presentation will focus on computational quantum chem. studies of proposed reaction mechanisms in the gas phase for direct oxidn. of melatonin. Geometry optimizations were performed using Hartree-Fock and D. Functional Theory methods in conjunction with Dunning's correlation-consistent polarized valence-only triple zeta (cc-pVTZ) basis set. Single point energies were calcd. using Moeller-Plesset perturbation theory in conjunction with cc-pVDZ, cc-pVTZ, and cc-pVQZ basis sets. Stable structures and conformations of melatonin radical intermediates will help understand how melatonin functions as an antioxidant and det. if a melatonin deriv. could function as a possible in vivo spin trap