High-contrast Cu(I)-selective Fluorescent Probes Based on Synergistic Electronic and Conformational Switching

The design of fluorescent probes for the detection of redox-active transition metals such as Cu(I/II) is challenging due to potentially interfering metal-induced non-radiative deactivation pathways. By using a ligand architecture with a built-in conformational switch that maximizes the change in donor potential upon metal binding and an electronically decoupled tunable pyrazoline fluorophore as acceptor, we systematically optimized the photoinduced electron transfer (PET) switching behavior of a series of Cu(I)-selective probes and achieved an excellent fluorescence enhancement of greater than 200-fold. Crystal structure analysis combined with NMR solution studies revealed significant conformational changes of the ligand framework upon Cu(I) coordination. The photophysical data are consistent with a kinetically controlled PET reaction involving only the ligand moiety, despite the fact that Cu(I)-mediated reductive quenching would be thermodynamically preferred. The study demonstrates that high-contrast ratios can be achieved even for redox-active metal cations, providing that the metal-initiated quenching pathways are kinetically unfavorable.