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Bright Zinc Probes with Thiomorpholine Monoxide Auxochromes for Imaging Insulin Secretion
Rundong Yu1,2, Junwei Zhang1, Xiaohong Peng3,4
1State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, National Biomedical Imaging Center, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China.
None:
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.

