The adverse health effects of air pollution around the world have been associated with the inhalation of fine particulate matter (PM2.5). Such outcomes are thought to be related to the induction of oxidative stress due to the excess formation of reactive oxygen species (ROS) in the respiratory and cardiovascular systems. The ability of airborne chemicals to deplete antioxidants and to form ROS is known as oxidative potential (OP). Here we studied the influence of aerosol acidity and organic ligands on the solubility of transition metals, in particular iron (Fe) and copper (Cu), and on the OP of PM2.5 from Canadian National Air Pollution Surveillance urban sites in Toronto, Vancouver, and Hamilton. Using chemical assays and model simulations of the lung redox chemistry, we quantified ROS formation in the lung lining fluid, targeting superoxide anion (O2 center dot-), hydrogen peroxide (H2O2), and hydroxyl radical (center dot OH), as well as the PM2.5 redox potential (RP). Experimental center dot OH formation (OPOH) showed high correlations with RP and model-predicted ROS metrics. Both aerosol acidity and oxalate content enhanced the solubility of transition metals, with oxalate showing a stronger association. While experimental OP metrics were primarily associated with species of primary origin such as elemental carbon, Fe, and Cu, model-predicted ROS were associated with secondary processes including proton-and ligand-mediated dissolution of Fe. Model simulations showed that water-soluble Cu was the main contributor to O2 center dot-formation, while water-soluble Fe dominated the formation of highly reactive center dot OH radical, particularly at study sites with highly acidic aerosol and elevated levels of oxalate. This study underscores the importance of reducing transition metal emissions in urban environments to improve population health.