Unique ratiometric fluorescent probe, a derivative of IndiFluors for pH mapping during mitophagy Subrata Munan and Animesh Samanta Shiv Nadar University, India Full-visible colour-tunable small molecular xenobiotics are at the forefront of bio-imaging research. 1 It received broad attention in multicolour organelles imaging through intracellular molecular interactions due to its non- invasive nature, simplicity, and high sensitivity. However, significant challenges are designing fluorophores with desired optical and biological properties due to their structural complexity. Here, we synthesized a unified interesting chemical toolbox,IndiFluors, which exhibited full-visible emission color (375-700 nm) by varying donor and acceptor strengths. 2 Encouraged by the excellent optical properties ofIndiFluors, we synthesized a unique small molecular morpholine conjugated probe,PM-Mor-OH as ratiometric fluorescent probe at a single excitation wavelength (λ ex. 488 nm). The lipophilic morpholine ligand has been extensively used to target lysosomes, but our probe unusually targets mitochondria. Casey et al. describe that mitochondrial functions are heavily influenced by acid−base homeostasis. 3 Therefore, elucidation of the mitochondrial pH and its alterations during mitochondrial damage is an interesting question that needs to be addressed in living cells. Herein, the morpholine ligand plays a pivotal role in modulating the emission ratio (λ green / red ) with internal pH variations (ΔpHi) via photo-induced electron transfer (PET).Consequently, the time-dependent density functional theory (TD-DFT) also well explained the bathochromic emission shift in basic pH through intramolecular charge transfer (ICT). Furthermore, PM-Mor-OH was successfully applied to quantify the mitochondrial pH ratiometrically when treated with mitophagy-induced rapamycin, A53T α-synuclein misfolded protein, and starvation. In addition, it can monitor mCherry Parkin’s translocation from cytoplasm to damaged mitochondria. Thus,PM-Mor-OHis a suitable probe for measuring ΔpHi when lysosomes fuse with damaged mitochondria, known as mitophagy. Thus,Itis a valuable probe for visualizing mitophagy and can be an appropriate chemical tool for diagnosing mitochondrial diseases.
References 1. Terai, T. Nagano, Curr. Opin. Chem. Biol., 2008, 12 ,515–521. 2. Munan, S. Kottarathil, M. M. Joseph, A. Jana, M. Ali, K. Mapa, K. K. Maiti and A. Samanta, ACS Sens., 2022, DOI: 10.1021/ acssensors.1c02381 3. J R Casey, S Grinstein and J Orlowski, Nat Rev Mol Cell Biol 11 , 50–61 (2010)
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