Luminescent Lanthanide Probes for Inorganic and Organic Phosphates

Abstract

Inorganic and organic phosphates‐including orthophosphate, nucleotides, and DNA‐are some of the most fundamental anions in cellular biology, regulating numerous processes of both medical and environmental significance. The characteristic long lifetimes of emitting lanthanides, including the brighter europium(III) and terbium(III), make them ideally suited for the development of molecular probes for the detection of phosphates directly in complex aqueous media. Moreover, given their high oxophilicity and the exquisite sensitivity of their quantum yields to their hydration number, those luminescent lanthanides are perfect for the detection of phosphates. Herein we discuss the principles that have guided the recent developments of molecular probes selective for inorganic or organic phosphates and how these lanthanide complexes facilitate the study of numerous biological processes.

Kinetically Inert Macrocyclic Europium(III) Receptors for Phosphate

“…Removing excess phosphate from blood without further decreasing bicarbonate levels is thus important. It should be noted, however, that there is no selectivity between orthophosphate and pyrophosphate, which is typical of receptors who operate through the direct phosphate coordination binding mode . This is not detrimental to our application given as excess orthophosphate should also be removed from the blood of hyperphosphatemic patients.…”

“…As phosphate or other anions coordinate Eu III , they displace the inner-sphere water molecules, resulting in an increase in both the luminescence intensity and the lifetimes of the excited states of the Eu III center. Together, these characteristics not only facilitate the study of anion recognition by aqueous Eu III complexes of 1,2-HOPO with open coordination sites but essentially render any such complex a luminescent probe. , …”

“…Importantly, the receptors also neither have any affinity for bicarbonate nor does bicarbonate affect coordination to phosphate. This selectivity for phosphate over bicarbonate is difficult to achieve for lanthanide-based receptors and probes, but it is crucial for the intended application. ,, Indeed, bicarbonate is present at much higher concentration in the blood (23–30 mM for HCO 3 – vs 0.8–1.45 mM for Pi), and 19.1% of patients with CKD, stages 4–5, suffer from low carbonate levels <22 mmol/L . Removing excess phosphate from blood without further decreasing bicarbonate levels is thus important.…”

“…With the goal of developing a new paradigm to the treatment of hyperphosphatemia via blood filtration, our group has developed inorganic phosphate receptors capable of removing phosphate from complex aqueous systems such as blood with high affinity and high selectivity over other endogenous anions . Due to their high oxophilicity and lability, lanthanide complexes − are better suited for this application than other metals such as copper, , zinc, − and iron . The key to achieving both sensitivity and selectivity in a flexible lanthanide­(III) receptor is to optimize the basicity of the chelating podand and the geometry of the ligand .…”

The urgent recognition of phosphate resource scarcity and pollution

“…2). [30][31][32] These innovations will require vertical integration to facilitate novel discoveries; lanthanides used in phosphate binders could be more readily accessible. However, limitations in the purication process have led to higher prices, despite them being more abundant than traditional metals such as gold.…”