Design and applications of metal-based molecular receptors and probes for inorganic phosphate

Inorganic phosphate has numerous biomedical functions. Regulated primarily by the kidneys, phosphate reaches abnormally high blood levels in patients with advanced renal diseases. Since phosphate cannot be efficiently removed by dialysis, the resulting hyperphosphatemia leads to increased mortality. Phosphate is also an important component of the environmental chemistry of surface water. Although required to secure our food supply, inorganic phosphate is also linked to eutrophication and the spread of algal blooms with an increasing economic and environmental burden. Key to resolving both of these issues is the development of accurate probes and molecular receptors for inorganic phosphate. Yet, quantifying phosphate in complex aqueous media remains challenging, as is the development of supramolecular receptors that have adequate sensitivity and selectivity for use in either blood or surface waters. Metal-based receptors are particularly well-suited for these applications as they can overcome the high hydration enthalpy of phosphate that limits the effectiveness of many organic receptors in water. Three different strategies are most commonly employed with inorganic receptors for anions: metal extrusion assays, responsive molecular receptors, and indicator displacement assays. In this review, the requirements for molecular receptors and probes for environmental applications are outlined. The different strategies deployed to recognize and sense phosphate with metal ions will be detailed, and their advantages and shortfalls will be delineated with key examples from the literature.