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

Mandapati V. Ramakrishnam Raju, Sarah M. Harris, Valérie C. Pierre

Research output: Contribution to journalReview articlepeer-review

31 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1090-1108
Number of pages19
JournalChemical Society Reviews
Issue number4
StatePublished - Feb 21 2020

Bibliographical note

Funding Information:
The authors acknowledge the support of the National Science Foundation provided by INFEWS N/P/H2O:SusChEM CHE-1610832.

Funding Information:
Dr Pierre obtained her Diplôme d’Ingénieur from Lyon, France, in 2001. She then moved to the University of California at Berkeley where she received her PhD in 2005 under the supervision of Dr Kenneth Raymond on the development of high relaxivity gadolinium contrast agents for MRI. Following a postdoctoral scholarship with Jacqueline K. Barton at California Institute of Technology where she studied supramolecular recognition of DNA by metal complexes, she joined the University of Minnesota, Twin-Cities, in 2007. She is currently an Associate Professor of Chemistry and Medicinal Chemistry and is the recipient of a CAREER award from the NSF and the Edward Stiefel award in bioinorganic chemistry, and named an Emerging Investigator in Bioinorganic Chemistry by the American Chemical Society and a New Talent: Americas by the Royal Society of Chemistry.

Publisher Copyright:
© The Royal Society of Chemistry 2020.

PubMed: MeSH publication types

  • Journal Article
  • Review


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