Selective Recognition of Physiological Phosphates by Luminescent Europium(III) Probes via Analyte‐Specific Energy‐Transfer Pathways

Abstract The physiological phosphates (PPs) are crucial in various biochemical pathways and bioenergetics. Their dysregulation is associated with multiple cellular dysfunctions and life‐threatening diseases. Designing sensitive and selective bioresponsive probes capable of differentiating Pi/NPPs levels is crucial for diagnostics and therapy. Developing probes for selective discrimination of phosphates faces intrinsic challenges due to their high hydration energy (ΔG hyd ) barrier and structural similarity. The hard Ln(III) ions can overcome the high ΔG hyd barrier and are ideal for the detection and discrimination of PPs due to their longer lifetimes, using time‐resolved luminescence (TRL) assays. Herein, two water‐soluble luminescent Eu(III) probes, [ Eu.L1 ] and [ Eu.L2 ], can discriminate physiological inorganic (Pi) and nucleoside polyphosphates (NPPs) in H 2 O based on their differential binding interaction with the respective probe, triggering analyte‐specific energy‐transfer pathways. We established the involvement of coordinative unsaturation and π ‐ π stacking interaction between the [ Eu.L ] probes and PPs, which modulates the nonradiative vibrational energy transfer (VET) and photo‐induced electron transfer (PeT) pathways, responsible for their specific luminescence response and selectivity. The interaction of phosphates with the Eu(III) probes were monitored by TRL spectroscopy, lifetime ( τ ) and hydration state ( q ) measurements, and 31 P NMR spectroscopy. These results connect the intricate molecular interactions of the [ Eu.L ] probes with PPs with concomitant TRL‐responses.