# Bright Zinc Probes with Thiomorpholine Monoxide Auxochromes for Imaging Insulin Secretion

## TL;DR

Scientists developed new zinc probes that improve imaging of insulin secretion in mouse islets with minimal harm.

## Contribution

The novel PKZnBR probes have enhanced fluorescence and reduced phototoxicity for long-term insulin secretion imaging.

## Key findings

- PKZnBR probes have fluorescence quantum yields up to seven times higher than PKZnRs due to TICT state inhibition.
- PKZnBR-3 shows a high turn-on ratio (134) and 340 nM affinity for zinc, suitable for ex vivo insulin secretion studies.
- The probes enable long-term, low-toxicity imaging of zinc and insulin corelease in mouse islets.

## 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
10.1002/anie.20210951034423531). 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.