A forefront of the research on Alzheimer's disease (AD) is the interaction of amyloid beta (A beta) peptides with redox metal ions (e.g., Cu(II), Fe(III), and Fe(II)) and the biological relevance of the A beta-metal complexes to neuronal cell loss and homeostasis of essential metals and other cellular species. This work is concerned with the kinetic and mechanistic studies of the ascorbic acid oxidation reaction by molecular oxygen that is facilitated by Cu(II) complexes with A beta(1-16), A beta(1-42), and aggregates of A beta(1-42). The reaction rate was found to linearly increase with the concentrations of A beta Cu(II) and dissolved oxygen and be invariant with high ascorbic acid concentrations. The rate constants were measured to be 117.2 +/-15.4 and 15.8 +/- 2.8 M-1 s(-1) at low (<100 mu M) and high AA concentrations, respectively. Unlike free Cu(II), in the presence of AA. A beta Cu(II) complexes facilitate the reduction of oxygen by producing H2O2 as a major product. Such a conclusion is drawn on the basis that the reaction stoichiometry between AA and O-2 is 1:1 when the A beta concentration is kept at a much greater value than that of Cu(II). A mechanism is proposed for the AA oxidation in which the oxidation states of the copper center in the A beta complex alternates between 2+ and 1+. The catalytic activity of Cu(II) toward O-2 reduction was found to decrease in the order of free Cu(II) > A beta(1-16)-Cu(II) > A beta(1-42)-Cu(II) > Cu(II) complexed by the A beta oligomer/fibril mixture > Cu(II) in A beta fibrils. The finding that Cu(II) in oligomeric and fibrous A beta aggregates possesses considerable activity toward H2O2 generation is particularly significant, since in senile plaques of AD patients the coexisting copper and A beta aggregates have been suggested to inflict oxidative stress through the production of reactive oxygen species (ROS). Although Cu(II) hound to oligomeric and fibrous A beta aggregates is less effective than free Cu(II) and the monomeric A beta Cu(II) complex in producing ROS, in vivo the Cu(II)-containing A beta oligomers and fibrils might be more biologically relevant given their stronger association with cell membranes and the closer proximity of ROS to cell membranes.