Histochemistry and Cell Biology

, Volume 139, Issue 5, pp 623–637 | Cite as

Uptake and localisation of small-molecule fluorescent probes in living cells: a critical appraisal of QSAR models and a case study concerning probes for DNA and RNA

  • Richard W. Horobin
  • Juan C. Stockert
  • F. Rashid-Doubell


Small-molecule fluorochromes are used in biology and medicine to generate informative microscopic and macroscopic images, permitting identification of cell structures, measurement of physiological/physicochemical properties, assessment of biological functions and assay of chemical components. Modes of uptake and precise intracellular localisation of a probe are typically significant factors in its successful application. These processes and localisations can be predicted using quantitative structure activity relations (QSAR) models, which correlate aspects of the physicochemical properties of the probes (expressed numerically) with the uptake/localisation. Pay-offs of such modelling include better understanding and trouble-shooting of current and novel probes, and easier design of future probes (“guided synthesis”). Uptake models discussed consider adsorptive (to lipid or protein domains), phagocytic and pinocytotic endocytosis, as well as passive diffusion. Localisation models discussed include those for cytosol, endoplasmic reticulum, Golgi apparatus, lipid droplets, lysosomes, mitochondria, nucleus and plasma membrane. A case example illustrates how such QSAR modelling of probe interactions can clarify localisation and mode of binding of probes to intracellular nucleic acids of living cells, including not only eukaryotic chromatin DNA and ribosomal RNA, but also prokaryote chromosomes.


Chromatin DNA Nucleus Nucleolus RNA Staining mechanism 



We thank Dr R Aitken, School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, for provision of facilities to one of us (RWH); and thank Drs M Cañete, A Villanueva, A Blázquez-Castro and J Espada for valuable collaboration. We also thank M Hope-Roberts, of Arcana Scientific and Medical Translations, Sheffield, UK, for drawing our attention to DB1582 and Dye 9. This work was partially supported by a Grant (CTQ2010-20870-C03-03), from the Ministerio de Ciencia e Innovación, Spain.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Richard W. Horobin
    • 1
  • Juan C. Stockert
    • 2
  • F. Rashid-Doubell
    • 3
  1. 1.School of Life Sciences, College of Medical, Veterinary and Life SciencesThe University of GlasgowGlasgowScotland, UK
  2. 2.Department of Biology, Faculty of SciencesAutonomous University of MadridMadridSpain
  3. 3.School of MedicineRoyal College of Surgeons in Ireland, BahrainBusaiteenKingdom of Bahrain

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