Enhanced selectivity for Mg with a phosphinate-based chelate: APDAP versus APTRA.

o-Aminophenol-N,N,O-triacetate, known as APTRA, is one of the most well-established ligands for targeting magnesium ions but, like other aminocarboxylate ligands, it binds Ca much more strongly than Mg. The synthesis of an O-phosphinate analogue of APTRA is reported here, namely o-aminophenol-N,N-diacetate-O-methylene-methylphosphinate, referred to as APDAP. Metal binding studies monitored using UV-visible spectroscopy show that the affinity of APDAP for Ca is reduced by over two orders of magnitude compared to APTRA, and for Zn by over three orders of magnitude, whereas the affinity for Mg is attenuated to a much lesser extent, by a factor of only about 7. The selectivity towards Mg is thus substantially improved. DFT calculations support the notion that longer P-O and P-C bonds in APDAP (compared to corresponding C-O and C-C bonds in APTRA) favour a larger angle at the metal, an effect that is less unfavourable for smaller ions like Mg than for larger ions such as Ca. Derivatives of APDAP can be anticipated that will offer improved sensing of Mg in the presence of Ca, in the physiologically important millimolar concentration range.