High Photostability in Nonconventional Coumarins with Far-Red/NIR Emission through Azetidinyl Substitution

Albert Gandioso, Marta Palau, Roger Bresolí-Obach, Alex Galindo, Anna Rovira, Manel Bosch, Santi Nonell, Vicente Marchán

Research output: Indexed journal article Articlepeer-review

29 Citations (Scopus)


Replacement of electron-donating N,N-dialkyl groups with three- or four-membered cyclic amines (e.g., aziridine and azetidine, respectively) has been described as a promising approach to improve some of the drawbacks of conventional fluorophores, including low fluorescent quantum yields (ÎF) in polar solvents. In this work, we have explored the influence of azetidinyl substitution on nonconventional coumarin-based COUPY dyes. Two azetidine-containing scaffolds were first synthesized in four linear synthetic steps and easily transformed into far-red/NIR-emitting fluorophores through N-alkylation of the pyridine moiety. Azetidine introduction in COUPY dyes resulted in enlarged Stokes' shifts with respect to the N,N-dialkylamino-containing parent dyes, but the ÎF were not significantly modified in aqueous media, which is in contrast with previously reported observations in other fluorophores. However, azetidinyl substitution led to an unprecedented improvement in the photostability of COUPY dyes, and high cell permeability was retained since the fluorophores accumulated selectively in mitochondria and nucleoli of HeLa cells. Overall, our results provide valuable insights for the design and optimization of novel fluorophores operating in the far-red/NIR region, since we have demonstrated that three important parameters (Stokes' shifts, ÎF, and photostability) cannot be always simultaneously addressed by simply replacing a N,N-dialkylamino group with azetidine, at least in nonconventional coumarin-based fluorophores.

Original languageEnglish
Pages (from-to)11519-11531
Number of pages13
JournalJournal of Organic Chemistry
Issue number19
Publication statusPublished - 5 Oct 2018


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