Novel turn-on fluorescent biosensors for selective detection of cellular Fe3+ in lysosomes: Thiophene as a selectivity-tuning handle for Fe3+ sensors

Bumhee Lim, Byungyeob Baek, Kyungkuk Jang, Na Keum Lee, Ji Hye Lee, Yeongcheol Lee, Jinwoo Kim, San Won Kang, Jaehyun Park, Suzi Kim, Nae Won Kang, Suckchang Hong, Dae Duk Kim, Ikyon Kim, Hyonseok Hwang, Jeeyeon Lee

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Abstract

Iron-selective turn-on sensors are indispensable tools for understanding iron-related cell death processes and human diseases. In this study, we report a novel class of fluorescent sensors derived from an indolizino[3,2-c]quinoline scaffold that exhibit high selectivity for Fe3+ over other biologically abundant cations in cells, including Fe2+, Al3+, Zn2+, and Mn2+. IQ18 works as a ratiometric sensor with a Kd value of 7.1 × 10 −7 M and a detection limit of 5.2 nM in ethanol, whereas IQ44 displays fluorescence enhancement upon binding with Fe3+ in both ethanol and water. In aqueous solution, IQ44 exists as 150-nm nanoparticles. The suppressed fluorescent emission of IQ44 nanoparticles in water is switched on in response to Fe3+, working as a turn-on nanoparticle sensor. Structure-property relationship analysis with IQ derivatives revealed that the thiophene ring confers selectivity for Fe3+. By installing thiophene in IQ44 as a selectivity-tuning handle, fluorescence in the presence of Fe3+ resulting from restriction of intramolecular rotation (RIR)and increased torsion angle induced by iron demonstrated that IQ44 is specifically localized in lysosomes, where it recognizes cellular Fe3+ in live cells, as determined using confocal microscopy. In addition, the increased fluorescent puncta of IQ44 in the presence of Fe3+ colocalized well with the RFP-tagged LC3 proteins (pmRFP-LC3), enabling the detection of the autophagy process.

Original languageEnglish
Pages (from-to)51-59
Number of pages9
JournalDyes and Pigments
Volume169
DOIs
Publication statusPublished - 2019 Oct

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All Science Journal Classification (ASJC) codes

  • Chemical Engineering(all)
  • Process Chemistry and Technology

Cite this

Lim, B., Baek, B., Jang, K., Lee, N. K., Lee, J. H., Lee, Y., Kim, J., Kang, S. W., Park, J., Kim, S., Kang, N. W., Hong, S., Kim, D. D., Kim, I., Hwang, H., & Lee, J. (2019). Novel turn-on fluorescent biosensors for selective detection of cellular Fe3+ in lysosomes: Thiophene as a selectivity-tuning handle for Fe3+ sensors. Dyes and Pigments, 169, 51-59. https://doi.org/10.1016/j.dyepig.2019.05.008