Hogg Christopher, Duncan Laura L, Parker David, Williams J A Gareth
Department of Chemistry, Durham University, South Road, Durham DH1 3LE, U.K.
Inorg Chem. 2025 May 19;64(19):9509-9518. doi: 10.1021/acs.inorgchem.5c00275. Epub 2025 May 7.
-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.
对氨基酚三乙酸酯（APTRA）是一种用于选择性结合镁的五齿配体。它已被纳入镁的荧光传感器中，尽管它对钙和锌的结合更强烈。在此，报道了APTRA的硫类似物的合成，即对氨基硫酚三乙酸酯，简称为S-APTRA。通过紫外吸收光谱法在缓冲水溶液中监测了这种新的五齿配体与锌、钙和镁的结合。用硫原子取代APTRA的酚氧使得S-APTRA能够在生物学相关范围内（Kd = 6.6 ± 0.3 nM）以对镁和钙的高选择性结合锌。对锌的选择性增强符合“硬软酸碱”原理。还报道了一种省略了连接硫的羧酸盐基团的四齿类似物S-APDIA。其较低的配位数导致对锌的亲和力降低（Kd = 8 ± 1 μM）。用间氯过氧苯甲酸（m-CPBA）氧化S-APTRA和S-APDIA会生成亚砜SO-APTRA和SO-APDIA，它们与锌的结合更弱（Kd分别为260 ± 20 mM和3.6 ± 0.3 mM）。这一新的配体家族在开发新型基于羧酸盐的锌传感器方面可能具有吸引力。
