biostudies-literatureKajino HNational Institute of Neurological Disorders and StrokeAgilent Technologies Japan LtdJapan Agency for Medical Research and DevelopmentNINDS NIH HHSNational Institutes of HealthNational Institute of General Medical SciencesNIGMS NIH HHS130422https://www.ebi.ac.uk/biostudies/studies/S-EPMC12704479biostudies-literatureUnknown130Rhodamines are useful fluorescent molecules for activity-based sensing. One powerful design strategy is to exploit changes in the open/closed equilibrium of rhodamine amides. In the context of amide derivatives of rhodamine B, a prototypical member of the rhodamine family, this strategy has been especially useful in the development of activity-based indicators for protons and metal ions. This is because at neutral pH, the closed form of rhodamine B amides dominates, making this otherwise bright and fluorescent dye non-fluorescent. At acidic pH, the equilibrium favors the open form. Despite a wealth of methods to trigger Lewis acid-mediated fluorogenicity of rhodamine B amides, there are far fewer ways to shift the open-close equilibrium to favor the open form at neutral pH. Here, we demonsBioorganic & medicinal chemistry lettersFluorogenic rhodamine B derivatives that become brighter at neutral pH.PMC12704479T32GM152983R01 NS098088T32 GM152983R01NS098088Kwon JHMiller EWKajino HfalseFluorogenic rhodamine B derivatives that become brighter at neutral pH.Rhodamines are useful fluorescent molecules for activity-based sensing. One powerful design strategy is to exploit changes in the open/closed equilibrium of rhodamine amides. In the context of amide derivatives of rhodamine B, a prototypical member of the rhodamine family, this strategy has been especially useful in the development of activity-based indicators for protons and metal ions. This is because at neutral pH, the closed form of rhodamine B amides dominates, making this otherwise bright and fluorescent dye non-fluorescent. At acidic pH, the equilibrium favors the open form. Despite a wealth of methods to trigger Lewis acid-mediated fluorogenicity of rhodamine B amides, there are far fewer ways to shift the open-close equilibrium to favor the open form at neutral pH. Here, we demons2025-01-01T00:00:00Z2025 Sep2026-06-06T03:41:45.639Z2026-05-25T03:08:03.675ZS-EPMC127044794103335910.1016/j.bmcl.2025.130422