With the support of the Chemical Mechanism, Function, and Properties Program of the Division of Chemistry, Professor Byron Purse of the Department of Chemistry and Biochemistry at San Diego State University is studying the design and properties of fluorescent nucleobase analogues (FBAs). FBAs are small synthetic molecules that mimic the natural genetic bases — adenine (A), cytosine (C), guanine (G), thymine (T), and uracil (U) — in DNA and RNA. Ideal FBAs preserve base-pairing properties while allowing sensitive detection of structural changes, molecular interactions, and other features relevant to genetic regulation. However, designing effective FBAs is challenging due to the difficulty of predicting how fluorescence responds in complex and dynamic biological environments like nucleic acids. This research aims to determine how molecular structure and local environment influence key FBA properties: brightness, photostability, and the ability to report on significant changes in biomolecular environment. The intellectual merit lies in advancing the understanding of how fluorophore chemical structure affects fluorescence and how fluorescence changes in response to the local chemical environment, and specifically when incorporated within DNA and RNA. Broader impacts include enabling new tools for genetic research and biotechnology, and training graduate students and undergraduates in synthetic and physical organic chemistry with interdisciplinary applications. Two fluorescent