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Synthesis and properties of water-soluble 1,9-dialkyl-substituted BF2 azadipyrromethene fluorophores

Abstract

Bis-alkylsulfonic acid and polyethylene glycol (PEG)-substituted BF2 azadipyrromethenes have been synthesized by an adaptable and versatile route. Only four synthetic stages were required to produce the penultimate fluorophore compounds, containing either two alcohol or two terminal alkyne substituents. The final synthetic step introduced either sulfonic acid or polyethylene glycol groups to impart aqueous solubility. Sulfonic acid groups were introduced by reaction of the bis-alcohol-substituted fluorophore with sulfur trioxide, and a double Cu(I)-catalyzed cycloaddition reaction between the bis-alkyne fluorophore and methoxypolyethylene glycol azide yielded a neutral bis-pegylated derivative. Both fluorophores exhibited excellent near-infrared (NIR) photophysical properties in methanol and aqueous solutions. Live cell microscopy imaging revealed efficient uptake and intracellular labelling of cells for both fluorophores. Their simple synthesis, with potential for last-step structural modifications, makes the present NIR-active azadipyrromethene derivatives potentially useful as NIR fluorescence imaging probes for live cells.

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Acknowledgements

This work is supported by the European Union’s Horizon 2020 research and innovation program, under the Marie-Sklodowska-Curie grant agreement No. 707618. DOS declares the following competing financial interest: patents have been filed on BF2-azadipyrro-methene-based NIR fluorophores (EP2493898 and US8907107).

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Correspondence to Donal F. O’Shea.

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Wu, D., Durán-Sampedro, G. & O’Shea, D.F. Synthesis and properties of water-soluble 1,9-dialkyl-substituted BF2 azadipyrromethene fluorophores. Front. Chem. Sci. Eng. 14, 97–104 (2020). https://doi.org/10.1007/s11705-019-1828-x

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Keywords

  • NIR-fluorophores
  • live cell imaging
  • NIR-AZA