CHIROPTICAL SENSING METHODOLOGY DEVELOPMENTS AND APPLICATIONS

In this project, Professor Christian Wolf’s research group of Georgetown University is developing optical sensing technology and innovative methods that accelerate the stereochemical analysis of challenging organic molecules including biologically active compounds and medicinally relevant disease biomarkers as well as complicated mixtures thereof without physical separation steps. This will overcome major obstacles and bottlenecks frequently encountered in academic and industrial chiral compound development programs and enable new opportunities and applications with generally available high-throughput screening, machine learning and chemometric data processing tools in currently not possible ways. This interdisciplinary project will involve collaborations with industrial and academic partners to provide unique educational and training opportunities for graduate, undergraduate and high school students as well as invaluable resources, e.g. industrial testing facilities and compound libraries. Chiroptical sensing methods that can be used to determine the absolute configuration, enantiomeric and diastereomeric ratios, and overall concentration of important but notoriously difficult compound classes (esters, amides, (thio)ethers, tertiary amines etc.) will be introduced. In addition, targeted sensing of two or more distant chirality centers in multifunctional molecules will be demonstrated as well as separation-free analysis of multicompound mixtures with assay arrays using multi-modal optical sensing methodology, Boolean-type molecular logic gates strategies and machine learning informed chemometric data processing. These goals will be achieved with new probe designs that operate in mechanistically distinct ways, including metal coordination, dynamic covalent chemistry, irreversible bond formation, halogen bonding etc. to rapidly capture the target and instantly transform molecular recognition via chirality amplification across stereodynamic receptor scaffolds, involvement of metal complex d-d transitions or charge transfer bands, exciton coupling effects etc. into quantifiable CD and UV signals. Finally, asymmetric catalysis with ammonia, water, hydrazine, hydroxylamine and carbon dioxide surrogates designed for chromatography-free reaction optimization will reveal the advantages of using integrated high-throughput chirality sensing and synthesis platforms, thereby advancing both fields. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.