Multidentate Europium Chelates as Luminoionophores for Anion Recognition: Impact of Ligand Design on Sensitivity and Selectivity, and Applicability to Enzymatic Assays

The design of photoluminescent molecular probes for the selective recognition of anions is a major challenge for the development of optical chemical sensors. The reversible binding of anions to lanthanide centers is one promising option for the realization of anion sensors, because it leads in some cases to a strong luminescence increase by the replacement of quenching water molecules. Yet, it is an open problem to gain control of the sensitivity and selectivity of the luminescence response. Primarily, the selective detection of (poly)phosphate species such as nucleotides has emerged as a demanding task, because they are involved in many biological processes and enzymatic reactions. We designed a series of pyridyl‐based multidentate europium complexes (seven‐, six‐, and five‐dentate) including sensitizing chromophores and studied their luminescence intensity and lifetime responses to different (poly)phosphates (adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), cyclic adenosine monophosphate (cAMP), pyrophosphate, and phosphate anions), and carboxyanions (citrate, malate, oxalacetate, succinate, α‐ketoglutarate, pyruvate, oxalate, carbonate). The results reveal that the number of free coordination sites has a significant impact on the sensitivity and selectivity of the response. Because of its reversibility, the lanthanide probes can be applied to monitor the activity of ATP‐consuming enzymes such ATPases and apyrases, which is demonstrated by means of the five‐dentate complex. Variation of binding sites: The number of binding sites of multidentate sensitizing ligands for EuIII can be easily varied. The resulting complexes show luminescence responses to certain anions such as adenosine triphosphate (ATP) or adenosine diphosphate with different sensitivity and selectivity. Hence, a five‐dentate complex was synthesized that undergoes a high and reversible response to ATP (see figure).