THEORETICAL PARAMETERS TO CHARACTERIZE ANTIOXIDANTS - PART 2 - THE CASES OF MELATONIN AND CARVEDILOL

This theoretical study focuses on two indole derivatives, melatonin (1 ) and carvedilol (8), with the objective of improving our understandin g of the molecular mechanisms underlying their radical-scavenging acti vity. Quantum-mechanical calculations were carried out using the AMI s emi-empirical method, some results being confirmed by nb initio (3-21G ) calculations. The quantum-chemical descriptor Delta H-ox (relative a diabatic oxidation potential) and the shape of the SOMO (singly occupi ed molecular orbital) indicate that the stabilization of its radical c ation can partially explain the well-documented antioxidant efficacy o f melatonin. This stabilization may result from electrostatic interact ions and from a hyperconjugative effect existing in a Family of confor mers of the melatonin radical cation having the side chain almost perp endicular to the plane of the aromatic rings. Furthermore, 6-hydroxyme latonin (7) appears to be a better free-radical scavenger than melaton in (1) in agreement with experimental results. According to the theore tical parameters Delta H-ox and Delta H-abs (relative bond dissociatio n enthalpy), carvedilol (8) is not a good antioxidant, in contrast to its ring-hydroxylated metabolites whose powerful antioxidant effects a re explained by the formation of an oxyl radical stabilized by delocal ization over the carbazole nucleus.