Lanthanide Supramolecular Phosphate Receptors for Environmental and Medical Applications

Abstract

Phosphate is ubiquitous in all forms of life and the environment. An essential nutrient for plants and humans, it is an increasingly important resource to meet the ever-increasing agricultural demand of modern society. However, excesses of phosphate can cause negative consequences: eutrophication of environmental waters can lead to harmful algal blooms, and excess phosphate in the blood (called hyperphosphatemia) leads to worsening prognoses for patients. Treatments for either problem are unsustainable or inefficient. The development of a more sustainable phosphate removal technology that is effective in water is needed. Small molecule phosphate receptors struggle to overcome the strong hydration shell of phosphate and display poor selectivity over other anions. Many metal-based receptors overcome the high hydration energies but also suffer from poor selectivity and stability in complex aqueous media. Lanthanide complexes, however, are well-suited to meet all of the requirements for phosphate removal from water. Their high coordination number and coordination chemistry allow for stable complexes with open sites to bind phosphate, and their Lewis acidities match the coordination chemistry of phosphate well for strong binding. This dissertation seeks to develop lanthanide-based phosphate receptors capable of binding phosphate with high affinity and selectivity for phosphate in water, develop a deeper understanding of the mechanism of phosphate binding, and develop a mechanism for controlled binding and release of phosphate. The in first study, we demonstrate that a lanthanide complex’s affinity for anions can be modulated by varying the coordinating group of the ligand. The basicity of the ligand affected the stability of the complex which was inversely proportional to the affinity of all anions to the receptor. Additionally, it was found that the difference in affinity between anions was due to the basicity of the anion rather than the Pearson’s hardness. Then, in the second study, we investigated the fluxionality of this category of lanthanide-based receptors and found that affinity and selectivity for phosphate is due only to the metal-anion interaction and not due to any preorganization like most other supramolecular receptors. NMR and computational studies confirmed that these complexes are highly fluxional and possess no secondary interaction with bound phosphate, yet still maintain excellent performance. In the third study, we investigated the trend in phosphate binding across the entire lanthanide series. Supporting the previous two studies, the affinity for phosphate increased as the Lewis acidity of the lanthanide increased. Surprisingly, the differences in affinity for phosphate across the series were drastic despite very small changes in the ionic radii and acidity of the metals. Lastly, we developed a lanthanide-based receptor which controlled phosphate binding and release electrostatically and allosterically. The concentration of chloride in solution controls the species coordinating to a palladium(II) ion peripheral to the phosphate binding site, forming an overall positive charge at low chloride concentration which binds phosphate, which could be switched to an overall negative change at high chloride concentration which releases the phosphate. Collectively, this dissertation advances the field of phosphate receptors, producing a library of complexes and insight into their future design and improvement to develop new phosphate removal systems which can recycle phosphate and “close the loop”.