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Zinc biology, featuring intertwining signaling networks and critical importance to human health, witnesses exciting opportunities in the big data era of physiology. Here, we report a class of red‐ and far‐red‐emitting Zn2+ probes with Kd values ranging from 190 nM to 74 μM, which are particularly suitable for real‐time monitoring the high concentration of Zn2+ co‐released with insulin during vesicular secretory events. Compared to the prototypical rhodamine‐based Zn2+ probes, the new class exploits morpholino auxochromes which eliminates phototoxicity during long‐term live recording of isolated islets. A Si‐rhodamine‐based Zn2+ probe with high turn‐on ratio (>100), whose synthesis was enabled by a new route featuring late‐stage N‐alkylation, allowed simultaneous recording of Ca2+ influx, mitochondrial signal, and insulin secretion in isolated mouse islets. The time‐lapse multicolor fluorescence movies and their analysis, enabled by red‐shifted Zn2+ and other orthogonal physiological probes, highlight the potential impact of biocompatible fluorophores on the fields of islet endocrinology and system biology. [ABSTRACT FROM AUTHOR]

Innentitelbild: Red- and Far-Red-Emitting Zinc Probes with Minimal Phototoxicity for Multiplexed Recording of Orchestrated Insulin Secretion (Angew. 4D islet physiology, biocompatibility, fluorescent probe, insulin secretion, zinc Keywords: 4D islet physiology; biocompatibility; fluorescent probe; insulin secretion; zinc EN 4D islet physiology biocompatibility fluorescent probe insulin secretion zinc 25790 25790 1 11/26/21 20211201 NES 211201 B Die Insulinsekretion b aus -Zellen kann nun zusammen mit dem Kalziumsignal und den Organellen aufgezeichnet werden. [Extracted from the article]

Inside Cover: Red- and Far-Red-Emitting Zinc Probes with Minimal Phototoxicity for Multiplexed Recording of Orchestrated Insulin Secretion (Angew. Keywords: 4D islet physiology; biocompatibility; fluorescent probe; insulin secretion; zinc EN 4D islet physiology biocompatibility fluorescent probe insulin secretion zinc 25586 25586 1 11/26/21 20211201 NES 211201 B Insulin secretion b from -cells in intact islets can now be recorded together with calcium signal and organelles. Tailored for 4D, long-term, and multiple-color recording of Zn SP 2+ sp /insulin co-secretion in -cells and islets, the new probes promise to unveil the spatial-temporal regulation of islet endocrinology. [Extracted from the article]