PhD Proposal: Jayashree Yalamanchili

Atmospheric aerosols (or particulate matter, PM) exert a number of adverse effects on human health. Among the diverse chemical constituents that make up atmospheric aerosols, transition metals have been hypothesized to possess an enhanced toxicity, based on their oxidative potential (OP)- the ability to support electron exchange and to catalyze and generate reactive oxygen species (ROS). The most widely used acellular assay for ROS measurements in PM – dithiothreitol (DTT) - uses phosphate (PO₄) buffers (pH = 7.4 and T = 37 °C) to simulate conditions in the human body. However, this assay matrix can induce changes in transition metals that may have profound effects on the assay results and their interpretation. The objective of this thesis is to characterize the fate of transition metals in OP assays that use a phosphate buffer matrix. The phenomena to be investigated include precipitation, co-precipitation, complexation with PO₄, adsorption, and oxidation of metals in the assay. We propose to first thermodynamically model the metal- buffer interactions for transition metals and to perform macroscopic experiments for qualitative analysis. We will then explore these interactions in the presence of an urban PM reference material at concentrations as would be in PM_2.5 samples to characterize metal transformations using colorimetric analysis of dissolved metals, laser particle light scattering measurements, and microscopic imaging. Finally, the effect of metal- phosphate buffer interaction on ROS generation in the DTT assay will be determined for metals present in different phases (aqueous vs solid). The results from this study will expand our knowledge on the plausible effects of using PO₄ based ROS assays to measure the toxicity of metals and guide modifications of these assays to mitigate this potentially widespread measurement artifact, ultimately improving understanding of PM toxicity.