1,8‐Naphthalimide Derivative Dyes with Large Stokes Shifts for Targeting Live‐Cell Mitochondria

An ideal fluorescent dye for staining cell organelles should have multiple properties including specificity, stability, biocompatibility, and a large Stokes shift. Tunable photophysical properties enable 1,8‐naphthalimide to serve as an excellent fluorophore in biomedical applications. Many naphthalimide derivatives have been developed into drugs, sensors, and other dyes. In this study, a series of 1,8‐naphthalimide derivatives targeting live cell mitochondria were synthesized. Among these probes, Mt‐4 was characterized as the best one, with highly specific mitochondrial localization, low cytotoxicity, and a large Stokes shift. More importantly, Mt‐4 stood out as a potential mitochondrial dye for living‐cell experiments involving induced mitochondrial stress arising from the treatments because Mt‐4 shows enhanced fluorescence in mitochondrial stress situations.

[1]  T. E. Thompson,et al.  Protonic conductance across phospholipid bilayer membranes induced by uncoupling agents for oxidative phosphorylation. , 1968, Proceedings of the National Academy of Sciences of the United States of America.

[2]  V. Skulachev,et al.  Mechanism of Coupling of Oxidative Phosphorylation and the Membrane Potential of Mitochondria , 1969, Nature.

[3]  L. B. Chen,et al.  Mitochondrial membrane potential in living cells. , 1988, Annual review of cell biology.

[4]  D. Andrews,et al.  An Introduction to Laser Spectroscopy , 1996 .

[5]  J C Reed,et al.  Mitochondria and apoptosis. , 1998, Science.

[6]  D. Wallace Mitochondrial diseases in man and mouse. , 1999, Science.

[7]  R. Youle,et al.  Dynamics of mitochondrial morphology in healthy cells and during apoptosis , 2003, Cell Death and Differentiation.

[8]  K. Mihara,et al.  Regulation of mitochondrial morphology by membrane potential, and DRP1-dependent division and FZO1-dependent fusion reaction in mammalian cells. , 2003, Biochemical and biophysical research communications.

[9]  N. Omenetto An Introduction to Laser Spectroscopy, 2nd Edition Edited by David L. Andrews (University of East Anglia, Norwich, U.K.) and Andrey A. Demidov (LaserSharp Corporation, Boston). Kluwer Academic/Plenum Publishers: New York. 2002. xii + 376 pp. $95.00. ISBN 0-306-47298-8. , 2003 .

[10]  Deirdre R. Meldrum,et al.  Life-on-a-chip , 2003, Nature Reviews Microbiology.

[11]  Xiaojun Peng,et al.  Heptamethine cyanine dyes with a large stokes shift and strong fluorescence: a paradigm for excited-state intramolecular charge transfer. , 2005, Journal of the American Chemical Society.

[12]  E. Sausville,et al.  Adaphostin and other anticancer drugs quench the fluorescence of mitochondrial potential probes , 2006, Cell Death and Differentiation.

[13]  D. Chan,et al.  Functions and dysfunctions of mitochondrial dynamics , 2007, Nature Reviews Molecular Cell Biology.

[14]  Yanqing Tian,et al.  Dually Fluorescent Sensing of pH and Dissolved Oxygen Using a Membrane Made from Polymerizable Sensing Monomers. , 2010, Sensors and actuators. B, Chemical.

[15]  Xianfeng Zhou,et al.  A series of naphthalimide derivatives as intra and extracellular pH sensors. , 2010, Biomaterials.

[16]  Sergio Grinstein,et al.  Sensors and regulators of intracellular pH , 2010, Nature Reviews Molecular Cell Biology.

[17]  D. Meldrum,et al.  A new highly selective fluorescent K+ sensor. , 2011, Journal of the American Chemical Society.

[18]  Jacqueline Cloos,et al.  Cell sensitivity assays: the MTT assay. , 2011, Methods in molecular biology.

[19]  M. Aleksandrova,et al.  Synthesis and electronic spectra of new low-molecular weight compounds with possible application in electroluminescent layers , 2011 .

[20]  B. Heyne,et al.  High Stokes shift anilido-pyridine boron difluoride dyes. , 2011, Angewandte Chemie.

[21]  Kenneth W Dunn,et al.  A practical guide to evaluating colocalization in biological microscopy. , 2011, American journal of physiology. Cell physiology.

[22]  M. Holl,et al.  New ratiometric optical oxygen and pH dual sensors with three emission colors for measuring photosynthetic activity in Cyanobacteria. , 2011, Journal of materials chemistry.

[23]  Xianfeng Zhou,et al.  An FRET-based ratiometric chemosensor for in vitro cellular fluorescence analyses of pH. , 2012, Biomaterials.

[24]  N. Tkachenko,et al.  Large Stokes shift fluorescent dyes based on a highly substituted terephthalic acid core. , 2012, Organic letters.

[25]  Deirdre R. Meldrum,et al.  Nanostructured Oxygen Sensor - Using Micelles to Incorporate a Hydrophobic Platinum Porphyrin , 2012, PloS one.

[26]  A. Mandal,et al.  A highly selective and efficient single molecular FRET based sensor for ratiometric detection of Fe3+ ions. , 2013, The Analyst.

[27]  T. Brown,et al.  Use of a large Stokes-shift fluorophore to increase the multiplexing capacity of a point-of-care DNA diagnostic device. , 2013, The Analyst.

[28]  T. Gunnlaugsson,et al.  Recent advances in the development of 1,8-naphthalimide based DNA targeting binders, anticancer and fluorescent cellular imaging agents. , 2013, Chemical Society reviews.

[29]  Alan R. Gillespie,et al.  Radiometric Normalization of Temporal Images Combining Automatic Detection of Pseudo-Invariant Features from the Distance and Similarity Spectral Measures, Density Scatterplot Analysis, and Robust Regression , 2013, Remote. Sens..

[30]  J. R. Corrêa,et al.  Selective mitochondrial staining with small fluorescent probes: importance, design, synthesis, challenges and trends for new markers , 2013 .

[31]  D. Meldrum,et al.  A dual sensor for real-time monitoring of glucose and oxygen. , 2013, Biomaterials.

[32]  Ben Zhong Tang,et al.  A photostable AIE luminogen for specific mitochondrial imaging and tracking. , 2013, Journal of the American Chemical Society.

[33]  D. Shangguan,et al.  A pH sensitive ratiometric fluorophore and its application for monitoring the intracellular and extracellular pHs simultaneously. , 2013, Journal of materials chemistry. B.

[34]  M. I. Rosa,et al.  Weekly fluconazole therapy for recurrent vulvovaginal candidiasis: a systematic review and meta-analysis. , 2013, European journal of obstetrics, gynecology, and reproductive biology.

[35]  Ricardo Massa Ferreira Lima,et al.  Reducing the Gap Between Business and Information Systems Through Complex Event Processing , 2013, Comput. Informatics.

[36]  Quantitatively Mapping Cellular Viscosity with Detailed Organelle Information via a Designed PET Fluorescent Probe , 2014, Scientific reports.

[37]  A polymer-based ratiometric intracellular glucose sensor† †Electronic supplementary information (ESI) available: The synthesis of a sensor, sensor selectivity, and co-localizations. See DOI: 10.1039/c4cc01110d Click here for additional data file. , 2014, Chemical communications.

[38]  Bethany J Wolf,et al.  Quantitative analysis of mitochondrial morphology and membrane potential in living cells using high-content imaging, machine learning, and morphological binning. , 2015, Biochimica et biophysica acta.