Tuning the electronic transition energy of indole via substitution: application to identify tryptophan-based chromophores that absorb and emit visible light

Phys Chem Chem Phys. 2021 Mar 21;23(11):6433-6437. doi: 10.1039/d0cp06710e. Epub 2021 Mar 12.

Abstract

Fluorescent amino acids (FAAs) offer significant advantages over fluorescent proteins in applications where the fluorophore size needs to be limited or minimized. A long-sought goal in biological spectroscopy/microcopy is to develop visible FAAs by modifying the indole ring of tryptophan. Herein, we examine the absorption spectra of a library of 4-substituted indoles and find that the frequency of the absorption maximum correlates linearly with the global electrophilicity index of the substituent. This finding permits us to identify two promising candidates, 4-formyltryptophan (4CHO-Trp) and 4-nitrotryptophan (4NO2-Trp), both of which can be excited by visible light. Further fluorescence measurements indicate that while 4CHO-indole (and 4CHO-Trp) emits cyan fluorescence with a reasonably large quantum yield (ca. 0.22 in ethanol), 4NO2-indole is essentially non-fluorescent, suggesting that 4CHO-Trp (4NO2-Trp) could be useful as a fluorescence reporter (quencher). In addition, we present a simple method for synthesizing 4CHO-Trp.

MeSH terms

  • Fluorescent Dyes / chemistry
  • Indoles / chemistry*
  • Light*
  • Quantum Theory
  • Spectrometry, Fluorescence
  • Tryptophan / chemistry*

Substances

  • Fluorescent Dyes
  • Indoles
  • Tryptophan