Structure–Function Analysis of Hydroxy-1,8-Naphthalimide Photoacids for ESPT-Driven H<sub>2</sub>S Probes
Trevor Dvorak, Sunayn Cheku, Linus Borer, Haley Hernandez-Sandoval, Kimberly A. Carlson, Haishi Cao
Abstract
High Resolution Image Download MS PowerPoint Slide Hydroxy-1,8-naphthalimides are a class of fluorophores known for their strong photoacidity, which facilitates excited-state proton transfer (ESPT) and results in red-shifted fluorescence emission. Based on this unique photophysical behavior, we synthesized and evaluated four reaction-based fluorescent probes (L1–L4) for the selective detection of hydrogen sulfide (H 2 S). Structure–function analysis revealed that the position of the hydroxyl substituent plays a critical role in modulating ESPT efficiency, emission wavelength, and overall probe sensitivity. Specifically, L1 (3-hydroxy) and L3 (4-hydroxy) exhibited distinct fluorescence maxima at 617 and 550 nm, respectively. Both probes demonstrated exceptionally fast reactivity with H 2 S, with L3 showing enhanced sensitivity attributed to the increased stability of its 4-naphtholate intermediate. In contrast, L4, bearing a 2,4-dinitrobenzene ether (DNBE) group, showed reduced sensitivity but maintained high selectivity for H 2 S over biologically relevant thiols such as l -cysteine and glutathione. These results defined key structure–activity relationships and offered design strategies for developing naphthalimide-based fluorescent probes for detecting reactive sulfur species.