Photophysical and Electrochemical Properties and Anticancer Activities of Porphyrin-Cored Fluorenodendrimers Synthesized by Click Chemistry

Abstract

A new class of porphyrin-cored fluorenodendrimers were synthesized by a convergent approach through click chemistry. The zeroth-, first-, and second-generation porphyrin-cored fluorenodendrimers were characterized by means of ¹H and ¹³C NMR spectroscopy, UV-vis spectroscopy, fluorescent spectroscopy, elemental analysis, and MALDI-TOF mass spectrometry. The UV-vis spectrum of the dendrimers showed an increase in the absorption intensity on increasing the dendrimer generation, and a bathochromic shift was observed for higher-generation dendrimers compared with lower-generation dendrimers. The dendrimers showed emission bands at 317, 604–668, and 617–668 nm, the intensity of which increased with increasing dendrimer generation. All the synthesized dendrimers exhibited a reversible oxidation potential in cyclic voltammetry. The therapeutic efficacy of the porphyrin-cored fluorenodendrimers for the inhibition of a growth tumor cell (PA-1) increased with increasing generation number of the dendrimer.

Key words

dendrimers - fluorenes - click chemistry - porphyrin - anticancer activity

• References

• 1 Dendrimers and other Dendritic Polymers . Tomalia DA. Fréchet JM. J. Wiley; Chichester: 2001
• 2 Hecht S. Fréchet JM. J. Angew. Chem. Int. Ed. 2001; 40: 74
• 3 Piotti ME. Rivera FJr. Bond R. Hawker CJ. Frechet JM. J. J. Am. Chem. Soc. 1999; 121: 9471
• 4 Günes S. Neugebauer H. Sariciftci NS. Chem. Rev. 2007; 107: 1324
• 5 Zhan X. Tan Z. Domercq B. An Z. Zhang X. Barlow S. Li Y. Zhu D. Kippelen B. Marder SR. J. Am. Chem. Soc. 2007; 129: 7246
• 6 Kira A. Umeyama T. Matano Y. Yoshida K. Isoda S. Park JK. Kim D. Imahori H. J. Am. Chem. Soc. 2009; 131: 3198
• 7a Denk W. Strickler JH. Webb WW. Science 1990; 248: 73
• 7b Zipfel WR. Williams RM. Webb WW. Nat. Biotechnol. 2003; 21: 1369
• 8 Nishiyama N. Stapert HR. Zhang G.-D. Takasu D. Jiang D.-L. Nagano T. Aida T. Kataoka K. Bioconjugate Chem. 2003; 14: 58
• 9 Minghao S. Zhishan B. J. Polym. Sci. Part A: Polym. Chem. 2007; 45: 111
• 10 Finikova O. Galkin A. Rozhkov V. Cordero M. Hägerhäll C. Vinogradov S. J. Am. Chem. Soc. 2003; 125: 4882
• 11 Kiran PP. Reddy DR. Maiya BG. Dharmadhikari AK. Kumar GR. Desai NR. Appl. Opt. 2002; 41: 7631
• 12 Perepichka DF. Bryce MR. Perepichka IF. Lyubchik SB. Christensen CA. Godbert N. Batsanov AS. Levillain E. McInnes EJ. L. Zhao JP. J. Am. Chem. Soc. 2002; 124: 14227
• 13 Gaylord BS. Heeger AJ. Bazan GC. J. Am. Chem. Soc. 2003; 125: 896
• 14a Ma H. Jen AK.-Y. Adv. Mater. (Weinheim, Ger.) 2001; 13: 1201
• 14b Goodson TG. III. Acc. Chem. Res. 2005; 38: 99
• 15 Bürgi L. Richards TJ. Friend RH. Sirringhaus H. J. Appl. Phys. 2003; 94: 6129
• 16 Belfield KD. Hagan DJ. Van Stryland EW. Schafer KJ. Negres RA. Org. Lett. 1999; 1: 1575
• 17 Sugou K. Sasaki K. Kitajima K. Iwaki T. Kuroda Y. J. Am. Chem. Soc. 2002; 124: 1182
• 18 Li L.-L. Diau EW.-G. Chem. Soc. Rev. 2013; 42: 291
• 19 Meldal CW. Tornoe C. Meldal M. J. Org. Chem. 2002; 67: 3057
• 20 Anandkumar D. Ganesan S. Rajakumar P. Maruthamuthu P. New J. Chem. 2017; 41: 11238
• 21 Rajakumar P. Raja R. Tetrahedron Lett. 2010; 51: 4365
• 22 Anandkumar D. Rajakumar P. Steroids 2017; 125: 37
• 23 Yao S. Belfield KD. J. Org. Chem. 2005; 70: 5126
• 24 Anandkumar D. Raja R. Rajakumar P. RSC Adv. 2016; 6: 25808
• 25 Lindsey JS. Schreiman IC. Hsu HC. Kearney PC. Marguerettaz AM. J. Org. Chem. 1987; 52: 827
• 26 Click Reaction: General Procedure A mixture of the appropriate alkyne (1.0 equiv), the appropriate azide-functionalized compound (1.2 equiv per azide functional unit), CuSO₄·5H₂O (5 mol %), and sodium ascorbate (10 mol%) in 3:1 THF–H₂O was stirred for 10 h at r.t. until the reaction was complete. The residue obtained after evaporation of the solvent was washed thoroughly with H₂O and dissolved in CHCl₃ (150 mL). The organic layer was separated, washed with brine (150 mL), dried (Na₂SO₄), and concentrated to give the crude triazole, which was purified by column chromatography (silica gel, CHCl₃–MeOH) Dendrimer 1 The reaction of dendritic azide 11 (0.091 g, 0.23 mmol, 1.0 equiv.) and porphyrin 22 (0.05 g, 0.06 mmol, 3.1 equiv) according to the general procedure, with elution by 19:1 CHCl₃–MeOH, gave a purple solid; yield: 0.1 g (74%); mp 132 °C. ¹H NMR (300 MHz, CDCl₃): δ = 0.60 (br s, 16 H); 0.76 (t, J = 6.3 Hz, 24 H), 1.04–1.11 (m, 48 H), 1.95 (d, J = 6 Hz, 16 H), 5.19 (s, 8 H), 5.57 (s, 8 H), 7.16–7.33 (m, 28 H), 7.53 (s, 4 H); 7.68 (d, J = 6.9 Hz, 8 H), 8.08 (d, J = 7.8 Hz, 8 H), 8.87 (s, 8 H). ¹³C NMR (75 MHz, CDCl₃ + DMSO-d ₆): δ = 14.0, 22.5, 23.7, 29.6, 31.4, 40.2, 54.6, 55.1, 62.1, 112.6, 119.9, 120.1, 120.2, 122.5, 122.7, 122.9, 126.9, 127.0, 127.5, 131.6, 132.9, 135.5, 136.4, 140.1, 141.9, 150.2, 150.8, 151.8, 157.7. MS (MALDI-TOF): m/z = 2476 [M + Na]⁺. Anal. Calcd For C₁₆₀H₁₇₆N₁₆O₄Zn: C, 78.35; H, 7.23; N, 9.14. Found: C, 78.23; H, 7.11; N, 9.2.