Bright Zinc Probeswith Thiomorpholine Monoxide Auxochromesfor Imaging Insulin Secretion

Zinc biology significantly impacts human physiological and pathological processes, especially for β-cell endocrinology. In 2021, our group reported the <b>PKZnR</b> 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 (<b>PKZnBR</b>) featuring thiomorpholine monoxide auxochromes with <i>K</i>_d values ranging from 160 nM to 94 μM. By inhibiting the twisted intramolecular charge transfer (TICT) state, the fluorescence quantum yields of <b>PKZnBRs</b> can be effectively increased to ∼7 times those of <b>PKZnRs</b>. A privileged candidate, <b>PKZnBR-3</b>, has a high turn-on ratio (∼134), appropriate affinity (340 nM), and excellent hydrophilicity, making it a powerful tool for long-term <i>ex vivo</i> recording of insulin secretion in mouse islets with minimal phototoxicity.