Enhanced Binding of Zn Using a Sulfur Version of -Aminophenol-Triacetate (APTRA): Introducing S-APTRA and Derivatives.

-aminophenol--triacetate (APTRA) is a pentadentate ligand adopted for the selective binding of Mg. It has been incorporated into fluorescent sensors for Mg, though it binds Ca and Zn more avidly. Here, the synthesis of a sulfur analogue of APTRA is reported, namely -aminothiophenol--triacetate, referred to as S-APTRA. The binding of this new pentadentate ligand to Zn, Ca, and Mg 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 Zn in a biologically relevant range ( = 6.6 ± 0.3 nM) with high selectivity over Mg and Ca. The enhanced selectivity for Zn 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 Zn ( = 8 ± 1 μM). The oxidation of S-APTRA and S-APDIA by -CPBA leads to the sulfoxides SO-APTRA and SO-APDIA, which bind Zn yet more weakly ( = 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.