An exploration of new avenues regarding deep tissue penetration and higher singlet oxygen efficiencies: novel near-IR photosensitizers for photodynamic therapy

A series of novel BODIPY-bearing electron-withdrawing groups at the meso position are reported here.According to the optical measurements, it may be clearly seen that the introduction of electron-donating groups into3,5-positions and the presence of electron-withdrawing groups at the meso position of the BODIPY core resulted inspectacular bathochromic shifts (up to ~ 304 nm), and the projected photosensitizers had absorption bands in thetherapeutic window of the electromagnetic spectrum (600–900 nm). The absorption maxima of compounds 4, 5, 6, and7 were at 886 nm, 890 nm, 760 nm, and 761 nm, respectively. The singlet oxygen generation experiments revealed thatcompounds 6 and 7, with high singlet oxygen quantum yields (0.52 and 0.93, respectively), were excellent and promisingcandidates for photodynamic therapy. The singlet oxygen quantum yield of 0.93 was the highest reported value so farfor BODIPY-based photosensitizers.

PDF

___

1. Kamat, M. A.; Hahn, N. M.; Efstathiou, J. A.; Lerner, S. P.; Malmström, P.; Choi, W.; Guo, C. C.; Lotan, Y.; Kassouf, W. Lancet 2016, 388, 2796-2810.
2. Gestaut, M. M.; Swanson, P. G. Reports of Practical Oncology and Radiotherapy 2017, 22, 77-82.
3. Taylor, C. W.; Kirby, A. M. Clin. Oncol. 2015, 27, 621-629.
4. Colagiuri, B.; Dhillon, H.; Butow, P. N.; Jansen, J.; Cox, K.; Jacquet, J. J. Pain Symptom Manag. 2013, 46, 275-281.
5. Wen, X.; Li, Y.; Hamblin, M. R. Photodiagn. Photodyn. 2017, 19, 140-152.
6. Dolmans, D. E.; Fukumura, D.; Jain, R. K. Nat. Rev. Cancer 2003, 3, 380-387.
7. Banerjee, S. M.; MacRobert, A. J.; Mosse, C. A.; Periera, B.; Bown, S. G.; Keshtgar, M. R. S. Breast 2017, 31, 105-113.
8. Richards-Kortumr, R.; Muraca, S. Annu. Rev. Phys. Chem. 1996, 47, 555-606.
9. Lu, H.; Mack, J.; Yanga, Y.; Shen, Z. Chem. Soc. Rev. 2014, 43, 4778-4823.
10. Kamkaew, A.; Lim, S. H.; Lee, H. B.; Kiew, L. V.; Chung, L. Y.; Burgess, K. Chem. Soc. Rev. 2013, 42, 77-88.
11. Loudet, A.; Burgess, K. Chem. Soc. Rev. 2007, 107, 4891-4932.
12. Ulrich, G.; Ziessel, R.; Harriman, A. Angew. Chem., Int. Ed. 2008, 47, 1184-1201.
13. Kilic, B.; Yesilgul, N.; Polat, V.; Gercek, Z.; Akkaya, E. U. Tetrahedron Lett. 2016, 57, 1317-1320.
14. Turan, I. S.; Cakmak, F. P.; Yildirim, D. C.; Cetin-Atalay, R.; Akkaya, E. U. Chem. Eur. J. 2014, 20, 16088-16092.
15. Zhang, X. F.; Yang, X. J. Phys. Chem. B 2013, 117, 5533-5539.
16. Cakmak, Y.; Kolemen, S.; Duman, S.; Dede, Y.; Dolen, Y.; Kilic, B.; Kostereli, Z.; Yildirim, L. T.; Dogan, A. L.; Guc, D. et al. Angew. Chem., Int. Ed. 2011, 50, 11937-11941.
17. Zhao, J.; Xu, K.; Yang, W.; Wang, Z.; Zhong, F. Chem. Soc. Rev. 2015, 44, 8904-8939.
18. Çetindere, S.; Oğuz-Tümay, S.; Kılıç, A.; Durmuş, M.; Yeşilot, S. Dyes Pigments 2017, 139, 517-523.
19. Awuah, S. A.; You, Y. RSC Adv. 2012, 2, 11169-11183.
20. Zhang, J.; Jiang, C.; Longo, J. P. F.; Azevedo, R. B.; Zhang, H.; Muehlmann, L. A. Acta Pharmaceutica Sinica B 2017, 8, 137-146.
21. Li, L.; Nguyen, B.; Burgess, K. Bioorg. Med. Chem. Lett. 2008, 18, 3112-3116.
22. Awuah, S. G.; Polreis, J.; Biradar, V.; You, Y. Org. Lett. 2011, 13, 3884-3887.
23. Sobenina, L. N.; Vasiltsov, A. M.; Petrova, O. V.; Petrushenko, K. B.; Ushakov, I. A.; Clavier, G.; Meallet-Renault, R.; Mikhaleva, A. I.; Trofimov, B. A. Org. Lett. 2011, 13, 2524-2527.
24. Li, L.; Nguyen, B.; Burgess, K. Bioorg. Med. Chem. Lett. 2008, 18, 3112-3116.
25. Petrushenko, K. B.; Petrushenko, I. K.; Petrova, O. V.; Sobenina, L. N.; Trofimov, B. A. Dyes Pigments 2017, 136, 488-495.
26. Afonin, A. V.; Ushakov, I. A.; Pavlov, D. V.; Petrova, O. V.; Sobenina, L. N.; Mikhaleva, A. I.; Trofimov, B. A. J. Fluorine Chem. 2013, 145, 51-57.
27. Yogo, T.; Urano, Y.; Ishitsuka, Y.; Maniwa, F.; Nagano, T. J. Am. Chem. Soc. 2005, 127, 12162-12163.
28. Epelde-Elezcano, N.; Martinez-Martinez, V.; Pena-Cabrera, E.; Gomez-Duran, C. F. A.; Arbeloa, I. L.; Lacombe, S. RSC Adv. 2016, 6, 41991-41998.
29. Gorbe, M.; Costero, A. M.; Sancenon, F.; Martinez-Manez, R.; Ballesteros-Cillero, R.; Ochando, L. E.; Chulvi, K.; Gotor, R.; Gil, S. Dyes Pigments 2019, 160, 198-207.
30. Davies, M. J. Biochem. Biophys. Res. Commun. 2003, 305, 761-770.
31. Xia, Q.; Boudreau, M. D.; Zhou, Y. T.; Yin, J. J.; Fu, P. P. J. Food Drug. Anal. 2011, 19, 396-402.
32. Cadet, J.; Ravanat, J. L.; Martinez, G. R.; Medeiros, M. H. G.; Mascio, P. D. Photochem. Photobiol. 2006, 82, 1219-1225.
33. Tørring, T.; Helmig, S.; Ogilby, P. R.; Gothelf, K. V. Acc. Chem. Res. 2014, 47, 1799-1806.
34. Zhang, C.; Zhao, J.; Wu, S.; Wang, Z.; Wu, W.; Ma, J.; Guo, S.; Huang, L. J. Am. Chem. Soc. 2013, 135, 10566-10578.
35. Lincoln, R.; Durantini, A. M.; Greene, L. E.; Martinez, S. R.; Knox, R.; Becerra, M. C.; Cosa, G. Photochem. Photobiol. Sci. 2017, 16, 178-184.
36. Mirenda, M.; Strassert, C. A.; Dicelio, L. E.; Roman, E. S. ACS Appl. Mater. Inter. 2010, 2, 1556-1560.
37. Senkuytu, E.; Ecik, E. T. Spectrochim. Acta A 2017, 182, 26-31.