Enhanced selectivity for Mg2+ with a phosphinate-based chelate: APDAP versus APTRA

Walter, Edward R.H.; Fox, Mark A.; Parker, David; Williams, J.A. Gareth

Abstract

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 Ca2+ much more strongly than Mg2+. 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 Ca2+ is reduced by over two orders of magnitude compared to APTRA, and for Zn2+ by over three orders of magnitude, whereas the affinity for Mg2+ is attenuated to a much lesser extent, by a factor of only about 7. The selectivity towards Mg2+ 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 Mg2+ than for larger ions such as Ca2+. Derivatives of APDAP can be anticipated that will offer improved sensing of Mg2+ in the presence of Ca2+, in the physiologically important millimolar concentration range.

Citation

Walter, E. R., Fox, M. A., Parker, D., & Williams, J. G. (2018). Enhanced selectivity for Mg2+ with a phosphinate-based chelate: APDAP versus APTRA. Dalton Transactions, 47(6), 1755-1763. https://doi.org/10.1039/c7dt04698g

• Journal Article Type: Article
• Acceptance Date: Jan 5, 2018
• Online Publication Date: Jan 16, 2018
• Publication Date: Feb 14, 2018
• Deposit Date: Jan 17, 2018
• Publicly Available Date: Jan 5, 2019
• Journal: Dalton Transactions
• Print ISSN: 1477-9226
• Electronic ISSN: 1477-9234
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 47
• Issue: 6
• Pages: 1755-1763
• DOI: https://doi.org/10.1039/c7dt04698g
• Public URL: https://durham-repository.worktribe.com/output/1368080