Designing magnesium-selective ligands using coordination chemistry principles

Progress in the selective binding and detection of magnesium ions has been slower than other biologically important divalent metal ions like calcium and zinc. The most widely used ligands for Mg²⁺ are by no means optimal, as they are not selective for it. Nevertheless, Mg²⁺ is a major cation in all cells, with physiologically critical functions. There is a need for improved sensors for Mg²⁺. In this review, we consider how an appreciation of fundamental coordination chemistry principles may inform the development of new ligands for Mg²⁺. A number of representative examples of ligands of differing denticity are discussed in this context. Low-denticity ligands such as β-keto acids offer the best selectivities, but speciation is an issue as other polydentate ligands such as pyrophosphate may complete the coordination sphere. High-denticity ligands based on aminocarboxylates such as APTRA typically offer the highest stability constants, but they bind Ca²⁺ and Zn²⁺ more strongly than Mg²⁺. We highlight recent examples featuring related aminophosphinates, where the longer bonds and smaller bite angles favour selectivity towards Mg²⁺. Macrocyclic receptors for magnesium are not discussed explicitly.