Fluorescent Probes that Span the Spectrum for Multi-Color Imaging of Peroxynitrite in Living Cells

Project Summary/Abstract Reactive oxygen species and reactive nitrogen species are oxidative metabolites that play important roles in human health and disease. While these oxidative metabolites are required for a diverse array of cellular processes, including cell death, differentiation, and signaling, uncontrolled production of reactive oxygen and nitrogen species can contribute to the underlying inflammation of cancer, heart disease, respiratory diseases, autoimmune diseases, and stroke. We are developing new imaging probes that span the visible spectrum to map reactive oxygen and nitrogen species with improved specificity and versatility to help understand the roles these oxidative metabolites play in inflammation. The scientific premise is that building an imaging toolkit for oxidative metabolites will provide new tools to further our understanding of the dynamics of reactive oxygen and nitrogen species in redox biology. This R15 application uses principles from physical organic chemistry, synthetic chemistry, and molecular probe design to develop new peroxynitrite-specific imaging probes with optical characteristics enable multi-analyte imaging. These tools will be applied in cell culture models of macrophages. Specifically, we will understand the structure-function relationship of diazaborines, a new motif for selective metabolite detection, and pursue diazaborine-based probes with excitation/emission profiles spanning from blue to green to red. Embedded in this work is a research-centric pedagogy to train undergraduates at the Colorado School of Mines to join an increasingly collaborative and diverse biomedical workforce.