Donor--Acceptor Based Amphiphilic Coumarin Conjugates: Design, Synthesis, and Photophysical Applications

Abstract

The development of fluorescent probes has attracted attention, due to their variety of applications, including detection of environment polarity, viscosity, ligand-receptor binding, drug-target binding, monitoring host-guest interactions and biophysical properties of the cell. However, these probes show several drawbacks like they do not function in the far-red region (600-700 nm), and display limited brightness due to the small extinction coefficients of their push-pull chromophores. Therefore, currently, intensive research is focusing on the design of polarity sensitive fluorogenic molecules of high brightness together with red-shifted emission. To address some of the above drawbacks, we focused our interest on amphiphilic Donor--Acceptor (D--A) based push-pull coumarin conjugates with promising photophysical properties, including emission in the far-red/near-infrared (NIR) region, large Stokes shifts, high photostability, excellent brightness and greater cell permeability required for bioimaging. 7-amino coumarin derivatives were efficiently synthesized from commercially available precursors. Subsequent condensation with 4-pyridylacetonitrile followed by N-alkylation by selecting the appropriate combination of the N-alkylating group (CH3, C8H17, and C18H37) required amphiphilic coumarins C1, C8 and C18 were obtained. These coumarin pyridinium derivatives show emission in the far-red region, large Stokes shifts in polar media, high photostability, and excellent brightness as compared to conventional coumarins. Photophysical properties of these three dyes (compound C1, C8 and C18) are studied in the different micellar medium (cationic, anionic and nonionic). A greater solubilisation for amphiphilic coumarins C8 and C18 was demonstrated compared to C1 probe. Presence of a hydrophobic alkyl chain helps to bind the molecule in the micellar interior. These dyes show excellent bacterial cell permeability as their fluorescence emission could be easily detected at a concentration as low as 0.5 μM. We anticipate that these coumarin scaffolds will open a way to the development of novel coumarin-based far-red to NIR emitting fluorophores with potential applications for organelle imaging and biomolecule labelling