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.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Yuan L, Lin W, Zheng K, He L, Huang W. Far-red to near infrared analyte-responsive fluorescent probes based on organic fluorophore platforms for fluorescence imaging. Chemical Society Reviews, 2013, 42(2): 622–661
Pansare V J, Hejazi S, Faenza W J, Prud’homme R K. Review of long-wavelength optical and NIR imaging materials: Contrast agents, fluorophores and multifunctional nano carriers. Chemistry of Materials, 2012, 24(5): 812–827
Ge Y, O’Shea D F. Azadipyrromethenes: From traditional dye chemistry to leading edge applications. Chemical Society Reviews, 2016, 45(14): 3846–3864
Killoran J, Allen L, Gallagher J F, Gallagher W M, O’Shea D F. Synthesis of BF2 chelates of tetraarylazadipyrromethenes and evidence for their photodynamic therapeutic behavior. Chemical Communications, 2002, 17: 1862–1863
Grossi M, Palma A, McDonnell S O, Hall M J, Rai D K, Muldoon J, O’ Shea D F. Mechanistic insight into the formation of tetraaryla-zadipyrromethenes. Journal of Organic Chemistry, 2012, 77(20): 9304–9312
O’ Connor A E, Mc Gee M M, Likar Y, Ponomarev V, Callanan J J, O’Shea D F, Byrne A T, Gallagher W M. Mechanism of cell death mediated by a BF2-chelated tetraaryl-azadipyrromethene photodynamic therapeutic: Dissection of the apoptotic pathway in vitro and in vivo. International Journal of Cancer, 2012, 130(3): 705–715
Cheung S, O’Shea D F. Directed self-assembly of fluorescence responsive nanoparticles and their use for real-time surface and cellular imaging. Nature Communications, 2017, 8(1): 1885
Wu D, O’Shea D F. Synthesis and properties of BF2-3,3′-dimethyldiarylazadipyrromethene near-infrared fluorophores. Organic Letters, 2013, 15(13): 3392–3395
Olmsted J. Calorimetric determinations of absolute fluorescence quantum yields. Journal of Physical Chemistry, 1979, 83(20): 2581–2584
Berlier J E, Rothe A, Buller G, Bradford J, Gray D R, Filanoski B J, Telford W G, Yue S, Liu J, Cheung C Y, et al. Quantitative comparison of long-wavelength alexa fluor dyes to cy dyes: Fluorescence of the dyes and their bioconjugates. Journal of Histochemistry and Cytochemistry, 2003, 51(12): 1699–1712
Wu D, Cheung S, Sampedro G, Chen Z L, Cahill R A, O’SheaD F. A DIE responsive NIR-fluorescent cell membrane probe. Biochimica et Biophysica Acta—Biomembranes, 2018, 1860(11): 2272–2280
Wu D, Daly H C, Conroy E, Li B, Gallagher W M, Cahill R A, O’Shea D F. PEGylated BF2-Azadipyrromethene (NIR-AZA) fluorophores, for intraoperative imaging. European Journal of Medicinal Chemistry, 2019, 161: 343–353
Daly H C, Sampedro G, Bon C, Wu D, Ismail G, Cahill R A, O’Shea D F. BF2-azadipyrromethene NIR-emissive fluorophores with research and clinical potential. European Journal of Medicinal Chemistry, 2017, 135: 392–400
Monopoli M P, Zendrini A, Wu D, Cheung S, Sampedro G, Ffrench B, Nolan J, Piskareva O, Stalings R L, Ducoli S, et al. Endogenous exosome labelling with an amphiphilic NIR-fluorescent probe. Chemical Communications, 2018, 54(52): 7219–7222
Denney D B, Smith L C, Song J, Rossi C J, Hall C D. Reactions of phosphoranes with peracids. Journal of Organic Chemistry, 1963, 28(3): 778–780
Yamamoto Y, Kurihara K, Yamada A, Takahashi M, Takahashi Y, Miyaura N. Intramolecular allylboration of γ-(ω-formylalkoxy) allylboronates for syntheses of trans- or cis-2-(ethenyl)tetrahydropyran-3-ol and 2-(ethenyl)oxepan-3-ol. Tetrahedron, 2003, 59(4): 537–542
Verbeek F P, van der Vorst J R, Schaafsma B E, Swijnenburg R J, Gaarenstroom K N, Elzevier H W, van de Velde C J, Frangioni J V, Vahrmeijer A L. Intraoperative near infrared fluorescence guided identification of the ureters using low dose methylene blue: A first in human experience. Journal of Urology, 2013, 190(2): 574–579
Al-Taher M, van den Bos J, Schols R M, Bouvy N D, Stassen L P. Fluorescence ureteral visualization in human laparoscopic colorectal surgery using methylene blue. Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A., 2016, 26(11): 870–875
Matsui A, Tanaka E, Choi H S, Kianzad V, Gioux S, Lomnes S J, Frangioni J V. Real-time, near-infrared, fluorescence-guided identification of the ureters using methylene blue. Surgery, 2010, 148(1): 78–86
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).
About this article
Cite this article
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
- live cell imaging