Bright Zinc Probes with Thiomorpholine Monoxide Auxochromes for Imaging Insulin Secretion

Abstract

Zinc biology significantly impacts human physiological and pathological processes, especially for β-cell endocrinology. In 2021, our group reported the PKZnR family with minimal phototoxicity and μM affinities for monitoring Zn²⁺/insulin corelease during vesicular secretory events on β-cells (Zhang et al. Angew. Chem. Int. Ed. 2021, 60 (49), 25846−25855). Here, we synthesized a series of Zn²⁺ probes (PKZnBR) featuring thiomorpholine monoxide auxochromes with K_d values ranging from 160 nM to 94 μM. By inhibiting the twisted intramolecular charge transfer (TICT) state, the fluorescence quantum yields of PKZnBRs can be effectively increased to ∼7 times those of PKZnRs. A privileged candidate, PKZnBR-3, has a high turn-on ratio (∼134), appropriate affinity (340 nM), and excellent hydrophilicity, making it a powerful tool for long-term ex vivo recording of insulin secretion in mouse islets with minimal phototoxicity.