Synthesis of Heavy-Atom-Free Triplet Photosensitizers Based on Organoboron Complexes

Abstract

A new class of organoboron complexes have been developed as heavy-atom-free triplet photosensitizers. A methodology was developed for the synthesis of an indolocarbazole–imine boron difluoride (IIBD) dye and its dimer from a 6-formylindolocarbazole. The IIBD dye was then coupled with a BODIPY dye through the C-2 or C-8 position of the latter to synthesize two dyads. Both dyads showed superior photophysical properties to those of the IIBD dyes. The relative triplet conversion efficiencies of these dyes were determined by measuring their singlet-oxygen (¹O₂) generation capacities. All the synthesized dyes showed high ¹O₂ generation compared with the BODIPY dye PM567. The dyad linked through the C-2 position of the BODIPY core showed the highest ¹O₂ generation efficiency, which could be useful for photodynamic therapy of cancers.

Key words

indolocarbazoles - dye - organoboron compounds - BODIPY dyes - triplet photosensitizers - photocatalysts

• References and Notes

• 1 Turro NJ, Ramamurthy V, Scaiano JC. Principles of Molecular Photochemistry: An Introduction 2009
• 2 Zhao J, Wu W, Sun J, Guo S. Chem. Soc. Rev. 2013; 42: 5323
• 3 Dolmans DE. J. G. J, Fukumura D, Jain RK. Nat. Rev. Cancer 2003; 3: 380
• 4a van Straten D, Mashayekhi V, de Bruijn HS, Oliveira S, Robinson DJ. Cancers 2017; 9: 19
• 4b Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, Moan J, Peng Q. J. Natl. Cancer. Inst. 1998; 90: 889
• 5 Gorman A, Killoran J, O’Shea C, Kenna T, Gallagher WM, O’Shea DF. J. Am. Chem. Soc. 2004; 126: 10619
• 6 Lim SH, Thivierge C, Nowak-Sliwinska P, Han J, van den Bergh H, Wagnières G, Burgess K, Lee HB. J. Med. Chem. 2010; 53: 2865
• 7 Zhang X, Wang Z, Hou Y, Yan Y, Zhao J, Dick B. J. Mater. Chem. C 2021; 9: 11944
• 8 Zhao J, Chen K, Hou Y, Che Y, Liu L, Jia D. Org. Biomol. Chem. 2018; 16: 3692
• 9 Ulrich G, Ziessel R, Harriman A. Angew. Chem. Int. Ed. 2008; 47: 1184
• 10a Mula S, Ray AK, Banerjee M, Chaudhuri T, Dasgupta K, Chattopadhyay S. J. Org. Chem. 2008; 73: 2146
• 10b Mula S, Frein S, Russo V, Ulrich G, Ziessel R, Barberá J, Deschenaux R. Chem. Mater. 2015; 27: 2332
• 10c Lu H, Mack J, Yang Y, Shen Z. Chem. Soc. Rev. 2014; 43: 4778
• 10d Poddar M, Misra R. Coord. Chem. Rev. 2020; 421: 213462
• 11 More AB, Mula S, Thakare S, Chakraborty S, Ray AK, Sekar N, Chattopadhyay S. J. Lumin. 2017; 190: 476
• 12a Turksoy A, Yildiz D, Akkaya EU. Coord. Chem. Rev. 2019; 379: 47
• 12b Kamkaew A, Lim SH, Lee HB, Kiew LV, Chung LY, Burgess K. Chem. Soc. Rev. 2013; 42: 77
• 13a Shivran N, Tyagi M, Mula S, Gupta P, Saha B, Patro BS, Chattopadhyay S. Eur. J. Med. Chem. 2016; 122: 352
• 13b Cheng T, Zhao Y, Li X, Lin F, Xu Y, Zhang X, Li Y, Wang R, Lai L. J. Chem. Inf. Model 2007; 47: 2140
• 14 Cakmak Y, Kolemen S, Duman S, Dede Y, Dolen Y, Kilic B, Kostereli Z, Yildirim LT, Dogan AL, Guc D, Akkaya EU. Angew. Chem. Int. Ed. 2011; 50: 11937
• 15a Mula S, Leclerc N, Lévêque P, Retailleau P, Ulrich G. J. Org. Chem. 2018; 83: 14406
• 15b Koli MR, Labiod A, Chakraborty S, Kumar M, Lévêque P, Ulrich G, Leclerc N, Jacquemin D, Mula S. ChemPhotoChem 2020; 4: 729
• 16 Gu R, Hameurlaine A, Dehaen W. J. Org. Chem. 2007; 72: 7207
• 17 Schmidt K, Brovelli S, Coropceanu V, Beljonne D, Cornil J, Bazzini C, Caronna T, Tubino R, Meinardi F, Shuai Z, Brédas J.-L. J. Phys. Chem. A 2007; 111: 10490
• 18 Thakare S, Stachelek P, Mula S, More AB, Chattopadhyay S, Ray AK, Sekar N, Ziessel R, Harriman A. Chem. Eur. J. 2016; 22: 14356
• 19 Mula S, Ulrich G, Ziessel R. Tetrahedron Lett. 2009; 50: 6383
• 20 Wang Z, Huang L, Yan Y, El-Zohry AM, Toffoletti A, Zhao J, Barbon A, Dick B, Mohammed OF, Han G. Angew. Chem. Int. Ed. 2020; 59: 16114
• 21 More AB, Mula S, Thakare S, Sekar N, Ray AK, Chattopadhyay S. J. Org. Chem. 2014; 79: 10981
• 22 Gupta M, Parvathi K, Mula S, Maity DK, Ray AK. Photochem. Photobiol. Sci. 2017; 16: 499
• 23a Gupta M, Mula S, Tyagi M, Ghanty TK, Murudkar S, Ray AK, Chattopadhyay S. Chem. Eur. J. 2013; 19: 17766
• 23b Loudet A, Burgess K. Chem. Rev. 2007; 107: 4891
• 24 Olmsted J. J. Phys. Chem. 1979; 83: 2581
• 25 Wilkinson F, Helman WP, Ross AB. J. Phys. Chem. Ref. Data 1993; 22: 113
• 26 Schiff Bases 2, 4, 8, and 13; General ProcedureThe appropriate aryl amine, a catalytic amount of PTS, and anhyd Na₂SO₄ (100 mg) were added to a solution of 12-pentyl-5,11-dihydroindolo[3,2-b]carbazole-6-carbaldehyde (1) in anhyd DCE (20 mL), and the mixture was stirred at 70 °C for 12 h. The mixture was then filtered and concentrated under vacuum, and the residue was subjected to column chromatography (basic alumina, EtOAc–hexane).Compound 4Prepared by following the general procedure from p-phenylenediamine (28 mg, 0.25 mmol) and 1 (200 mg, 0.56 mmol) in DCE (20 mL) and purified by column chromatography [basic alumina, hexane–EtOAc (70:30)] to give a red solid; yield: 142 mg (32%); mp >300 °C.¹H NMR (500 MHz, DMSO-d ₆, 25 °C, TMS): δ = 0.89 (t, J = 7.0 Hz, 3 H), 1.38–1.42 (m, 2 H), 1.58–1.60 (m, 2 H), 1.88–1.90 (m, 2 H), 3.16 (t, J = 8.0 Hz, 2 H), 7.24–7.30 (m, 2 H), 7.47–7.48 (m, 2 H), 7.64 (d, J = 8.0 Hz, 1 H), 7.87 (s, 2 H), 7.91 (d, J = 8.0 Hz, 1 H), 8.22 (d, J = 8.0 Hz, 1 H), 8.47 (d, J = 8.0 Hz, 1 H), 10.06 (s, 1 H), 11.43 (s, 1 H), 11.86 (s, 1 H). ¹³C{¹H} NMR (125 MHz, DMSO-d ₆, 25 °C, TMS): δ = 14.1, 22.3, 28.6, 28.8, 31.6, 109.8, 111.4, 111.9, 114.6, 118.8, 119.1, 120.3, 120.5, 121.8, 121.9, 122.1, 122.7, 123.1, 123.7, 125.3, 125.8, 134.3, 134.6, 140.6, 140.9, 141.6, 147.8, 152.0. EI-MS: m/z = 780.4 [M⁺].BF₂ Complexes 3, 5, 9, and 14; General ProcedureA mixture of the appropriate Schiff base and Et₃N in anhyd DCE was stirred at 25 °C for 15 min. BF₃·OEt₂ was then added dropwise and the resulting mixture was stirred at 70 °C overnight. The reaction was quenched with sat. aq NaHCO₃, and the mixture was extracted with CH₂Cl₂. The organic layer was washed with H₂O (3 × 50 mL) and dried (Na₂SO₄). After removal of the solvent under a vacuum, the residue was purified by column chromatography (silica gel).Compound 5Prepared by the reaction of 4 (121 mg, 0.16 mmol), Et₃N (0.3 mL, 1.86 mmol), and BF₃·OEt₂ (0.2 mL, 1.86 mmol) in DCE (10 mL) according to the general procedure. The crude product was purified by column chromatography [silica gel, EtOAc–PE (30:70)] to give a dark-blue solid; yield: 100 mg (73%); mp >300 °C.¹H NMR (500 MHz, DMSO-d ₆, 80 °C, TMS): δ = 0.93 (t, J = 7.0 Hz, 6 H), 1.45–1.46 (m, 4 H), 1.64–1.65 (m, 4 H), 1.97–1.98 (m, 4 H), 3.73 (t, J = 8.0 Hz, 4 H), 7.28 (s, 2 H), 7.42 (s, 2 H), 7.55 (s, 4 H), 7.71 (d, J = 7.5 Hz, 2 H), 7.88 (d, J = 7.5 Hz, 2 H), 8.08 (s, 4 H), 8.28 (d, J = 7.5 Hz, 2 H), 8.55 (d, J = 8.0 Hz, 2 H), 9.79 (s, 2 H), 11.61 (s, 2 H). ¹³C{¹H} NMR (125 MHz, DMSO-d ₆, 80 °C, TMS): δ = 13.3, 21.7, 28.4, 28.8, 31.1, 106.7, 111.7, 113.6, 116.2, 119.1, 119.6, 120.9, 121.9, 122.9, 123.8, 125.3, 125.7, 126.3, 133.9, 135.7, 139.9, 141.0, 143.1, 143.3, 158.0. EI-MS: m/z = 876.3 [M⁺].