Monitoring Lysosomal Viscosity in Hyperglycemia in Association with Ca ²⁺ Homeostasis and Alzheimer’s Disease Using a Fluorescent Zn–Metal Complex

A bright, photostable, and less-toxic fluorescent Zn–metal complex is reported to monitor lysosomal viscosity in hyperglycemia associated with Ca2+ homeostasis and in vivo Alzheimer’s disease. A series of Zn–salen (Sl) complexes (Zn–Sl–X), where X = methoxy (−OCH3), pyrrolidine (−Py), N,N-diethyl amine (−NEt2), and N-methyl-N-propyl morpholine (−MPM), were synthesized. Among them, the synergistic effect of MPM in the Zn–Sl–MPM complex efficiently acts as both a viscosity sensor and the specific staining agent for lysosomes. The pronounced fluorescence response within lysosomes arises due to restricted intramolecular rotation (RIR) of the MPM unit in a viscous medium under hyperglycemic conditions. Our findings suggested that lysosomal viscosity is exclusively associated with Ca2+ imbalance in hyperglycemia and in Alzheimer’s disease in vivo in Caenorhabditis elegans (C. elegans). Further, super-resolution radial fluctuation (SRRF) microscopy helped to observe the lysosomal swelling with an increased size in hyperglycemia.