Funct. Mater. 2024; 31 (3): 405-412.

doi:https://doi.org/10.15407/fm31.03.405

Synthesis, spectral-fluorescence properties and TD-DFT calculations of 4-cyanotryptophan and its derivatives

R.G. Shypov1, O.V. Buravov2,3, E.S. Gladkov1,2, L.V. Chepeleva1, A. V. Kyrychenko1,2

1 Institute of Chemistry and School of Chemistry, V. N. Karazin Kharkiv National University, 4 Svobody Sq., Kharkiv 61022, Ukraine
2 State Scientific Institution ′′Institute for Single Crystals′′, National Academy of Sciences of Ukraine, 60 Nauky Ave., Kharkiv 61072, Ukraine
3 Enamine Ltd., 67 Winston Churchill St., Kyiv 02660, Ukraine

Abstract: 

Tryptophan-based fluorescent amino acids are promising alternatives to native tryptophan (Trp) for biological fluorescence studies. This work reports the synthesis and structure characterization of 4-cyanotryptophan (4-CN-Trp) based on the modified Mannich reaction. The optical spectra of 4-CN-Trp measured in solvents of different natures revealed the essential red-shifted absorption and emission in aqueous solutions compared to unsubstituted Trp. Moreover, the high fluorescence quantum yield of 4-CN-Trp makes it a promising replacement for native Trp for the study of folding and denaturation of proteins containing several Trp residues. In addition, the TD-DFT calculations were utilized for computer-aided design of dicyano-substituted Trp, suggesting that 4,6- and 4,7-diCN-Trp are promising for protein studies due to their red-shifted fluorescence.

Keywords: 
organic synthesis, heterocycles, non-natural amino acid, fluorescent probe, DFT.

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