Enhanced Binding of Zn 2+ Using a Sulfur Version of o ‑Aminophenol-Triacetate (APTRA): Introducing S‑APTRA and Derivatives

Hogg, Christopher; Duncan, Laura L.; Parker, David; Williams, J. A. Gareth

Abstract

Ortho-aminophenol-N,N,O-triacetate (APTRA) is a pentadentate ligand adopted for the selective binding of Mg2+. It has been incorporated into fluorescent sensors for Mg2+, though it binds Ca2+ and Zn2+ more avidly. Here, the synthesis of a sulfur analogue of APTRA is reported, namely ortho-aminothiophenol-N,N,S-triacetate, referred to as S-APTRA. The binding of this new pentadentate ligand to Zn2+, Ca2+, and Mg2+ has been monitored in buffered aqueous solution by UV absorption spectroscopy. The replacement of the phenolic oxygen of APTRA by a sulfur atom renders S-APTRA capable of binding Zn2+ in a biologically relevant range (K d = 6.6 ± 0.3 nM) with high selectivity over Mg2+ and Ca2+. The enhanced selectivity for Zn2+ is in line with the principles of “hard and soft acids and bases.” A tetradentate analogue omitting the S-appended carboxylate group, S-APDIA, is also reported. Its lower denticity leads to decreased affinity for Zn2+ (K d = 8 ± 1 μM). The oxidation of S-APTRA and S-APDIA by m-CPBA leads to the sulfoxides SO-APTRA and SO-APDIA, which bind Zn2+ yet more weakly (K d = 260 ± 20 mM and 3.6 ± 0.3 mM, respectively). This new family of ligands may prove appealing in the development of new carboxylate-based zinc sensors.

Citation

Hogg, C., Duncan, L. L., Parker, D., & Williams, J. A. G. (2025). Enhanced Binding of Zn 2+ Using a Sulfur Version of o ‑Aminophenol-Triacetate (APTRA): Introducing S‑APTRA and Derivatives. Inorganic Chemistry, 64(19), 9509-9518. https://doi.org/10.1021/acs.inorgchem.5c00275

• Journal Article Type: Article
• Acceptance Date: Apr 29, 2025
• Online Publication Date: May 7, 2025
• Publication Date: May 19, 2025
• Deposit Date: Jul 1, 2025
• Publicly Available Date: Jul 1, 2025
• Journal: Inorganic Chemistry
• Print ISSN: 0020-1669
• Electronic ISSN: 1520-510X
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 64
• Issue: 19
• Pages: 9509-9518
• DOI: https://doi.org/10.1021/acs.inorgchem.5c00275
• Public URL: https://durham-repository.worktribe.com/output/3962616