Photophysical and Photochemical Properties of New Coumarin-Substituted Zinc and Indium Phthalocyanines for Photodynamic Therapy

Öz

In this study, we synthesized and characterized zinc (II) and indium (III) acetate phthalocyanine derivatives, modified with 7-hydroxy-8-methyl-4-(2,3,4,5-tetrafluorophenyl)coumarin, as potential photosensitizers for photodynamic therapy (PDT). The synthesized phthalocyanines were characterized using various analytical techniques, including elemental analysis, UV-Vis, FT-IR spectroscopy, and MALDI-TOF mass spectrometry. The study focused on the photophysical and photochemical properties of these compounds, particularly their singlet oxygen and photodegradation quantum yields. Zinc phthalocyanine exhibited lower fluorescence quantum yield and higher stability, whereas indium phthalocyanine showed superior singlet oxygen generation. These findings suggest that coumarin-substituted phthalocyanines hold promise as effective photosensitizers in PDT, with indium derivatives demonstrating enhanced photodynamic efficacy.

Anahtar Kelimeler

• Coumarin
• Phthalocyanine
• Photodynamic therapy
• PDT
• Singlet oxygen

Destekleyen Kurum

Marmara Üniversitesi

Proje Numarası

FYL-2022-10633

Teşekkür

We gratefully acknowledge the Research Foundation of Marmara University, Commission of Scientific Research Project (BAPKO) for their support under grant FYL-2022-10633.

Kaynakça

1. [1]. Yahya, M., Nural, Y., & Seferoğlu, Z. (2022). Recent advances in the nonlinear optical (NLO) properties of phthalocyanines: A review. Dyes and Pigments, 198, 109960. (https://doi.org/10.1016/j.dyepig.2021.109960)
2. [2]. Claessens, C. G., Hahn, U. W. E., & Torres, T. (2008). Phthalocyanines: From outstanding electronic properties to emerging applications. The Chemical Record, 8(2), 75-97. (https://doi.org/10.1002/tcr.20139)
3. [3]. Klyamer, D., Bonegardt, D., & Basova, T. (2021). Fluoro-substituted metal phthalocyanines for active layers of chemical sensors. Chemosensors, 9(6), 133. (https://doi.org/10.3390/chemosensors9060133)
4. [4]. Song, C., Li, Y., Gao, C., Zhang, H., Chuai, Y., & Song, D. (2020). An OTFT based on titanium phthalocyanine dichloride: A new p-type organic semiconductor. Materials Letters, 270, 127666. (https://doi.org/10.1016/j.matlet.2020.127666)
5. [5]. Molina, D., Follana-Berná, J., & Sastre-Santos, Á. (2023). Phthalocyanines, porphyrins and other porphyrinoids as components of perovskite solar cells. Journal of Materials Chemistry C, 11(24), 7885-7919. (https://doi.org/10.1039/D2TC04441B)
6. [6]. Rezaee, E., Khan, D., Cai, S., Dong, L., Xiao, H., Silva, S. R. P., Liu, X., & Xu, Z. X. (2023). Phthalocyanine in perovskite solar cells: A review. Materials Chemistry Frontiers, 7(9), 1704-1736. (https://doi.org/10.1039/D2QM01369J)
7. [7]. Yabaş, E., Biçer, E., & Altındal, A. (2023). Novel reduced graphene oxide/zinc phthalocyanine and reduced graphene oxide/cobalt phthalocyanine hybrids as high sensitivity room temperature volatile organic compound gas sensors. Journal of Molecular Structure, 1271, 134076. (https://doi.org/10.1016/j.molstruc.2022.134076)
8. [8]. Gursel, Y. H., Senkal, B. F., Kandaz, M., & Yakuphanoglu, F. (2009). Synthesis and liquid crystal properties of phthalocyanine bearing a star polytetrahydrofuran moiety. Polyhedron, 28(8), 1490-1496. (https://doi.org/10.1016/j.poly.2009.02.038)

9. [9]. Canımkurbey, B., Taşkan, M. C., Demir, S., Duygulu, E., Atilla, D., & Yuksel, F. (2020). Synthesis and investigation of the electrical properties of novel liquid-crystal phthalocyanines bearing triple branched alkylthia chains. New Journal of Chemistry, 44(18), 7424-7435. (https://doi.org/10.1039/D0NJ00678E)
10. [10]. Balamurugan, G., & Park, J. S. (2022). Enhanced solution processing and optical properties of perhalogenated zinc-phthalocyanines via anion-π bonding. Dyes and Pigments, 201, 110199. (https://doi.org/10.1016/j.dyepig.2022.110199)
11. [11]. Lo, P. C., Rodríguez-Morgade, M. S., Pandey, R. K., Ng, D. K., Torres, T., & Dumoulin, F. (2020). The unique features and promises of phthalocyanines as advanced photosensitisers for photodynamic therapy of cancer. Chemical Society Reviews, 49(4), 1041-1056. (https://doi.org/10.1039/C9CS00129H)
12. [12]. Zhang, Y., & Lovell, J. F. (2017). Recent applications of phthalocyanines and naphthalocyanines for imaging and therapy. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 9(1), e1420. (https://doi.org/10.1002/wnan.1420)
13. [13]. Çalık, A. E., Köksoy, B., Orman, E. B., Durmuş, M., Özkaya, A. R., & Bulut, M. (2013). 4-Carboxymethyl-8-methyl-7-oxycoumarin substituted zinc, cobalt and indium phthalocyanines: Electrochemical and photochemical properties. Journal of Porphyrins and Phthalocyanines, 17(10), 1046-1054. (https://doi.org/10.1142/S108842461350096X)
14. [14]. Saka, E. T., Göl, C., Durmuş, M., Kantekin, H., & Bıyıklıoğlu, Z. (2012). Photophysical, photochemical and aggregation behavior of novel peripherally tetra-substituted phthalocyanine derivatives. Journal of Photochemistry and Photobiology A: Chemistry, 241, 67-78. (https://doi.org/10.1016/j.jphotochem.2012.05.023)
15. [15]. Prabhu CP, K., Nemakal, M., Managa, M., Nyokong, T., & Koodlur Sannegowda, L. (2021). Symmetrically substituted Zn and Al phthalocyanines and polymers for photodynamic therapy application. Frontiers in Chemistry, 9, 647331. (https://doi.org/10.3389/fchem.2021.647331)
16. [16]. Neagu, M., Constantin, C., Tampa, M., Matei, C., Lupu, A., Manole, E., Ion, RM., Fenga, C., & Tsatsakis, A. M. (2016). Toxicological and efficacy assessment of post-transition metal (Indium) phthalocyanine for photodynamic therapy in neuroblastoma. Oncotarget, 7(43), 69718. (https://doi.org/10.18632/oncotarget.11942)
17. [17]. Özdemir, M., Köksoy, B., Yalçın, B., Taşkın, T., Selçuki, N. A., Salan, Ü., Durmuş, M., & Bulut, M. (2021). Novel lutetium (III) phthalocyanine-coumarin dyads; synthesis, characterization, photochemical, theoretical and antioxidant properties. Inorganica Chimica Acta, 517, 120145. (https://doi.org/10.1016/j.ica.2020.120145)
18. [18]. Sharma, D., Steen, G., Korterik, J. P., García-Iglesias, M., Vázquez, P., Torres, T., Herek, J. L., & Huijser, A. (2013). Impact of the anchoring ligand on electron injection and recombination dynamics at the interface of novel asymmetric push–pull zinc phthalocyanines and TiO2. The Journal of Physical Chemistry C, 117(48), 25397-25404. (https://doi.org/10.1021/jp410080a)
19. [19]. Kwiatkowski, S., Knap, B., Przystupski, D., Saczko, J., Kędzierska, E., Knap-Czop, K., Kotlińska, J., Michel, O., Kotowski, K., & Kulbacka, J. (2018). Photodynamic therapy–mechanisms, photosensitizers and combinations. Biomedicine & pharmacotherapy, 106, 1098-1107. (https://doi.org/10.1016/j.biopha.2018.07.049)
20. [20]. Köksoy, B., Durmuş, M., & Bulut, M. (2019). Potential photosensitizer candidates for PDT including 7-oxy-3-thiomethylphenyl coumarino-phthalocyanines. Inorganica Chimica Acta, 498, 119137. (https://doi.org/10.1016/j.ica.2019.119137)
21. [21]. Rak, J., Kabesova, M., Benes, J., Pouckova, P., & Vetvicka, D. (2023). Advances in liposome-encapsulated phthalocyanines for photodynamic therapy. Life, 13(2), 305. (https://doi.org/10.3390/life13020305)
22. [22]. Supuran, C. T. (2020). Coumarin carbonic anhydrase inhibitors from natural sources. Journal of Enzyme Inhibition and Medicinal Chemistry, 35(1), 1462-1470. (https://doi.org/10.1080/14756366.2020.1788009)
23. [23]. Özdemir, M., Taşkın, D., Ceyhan, D., Köksoy, B., Taşkın, T., Bulut, M., & Yalçın, B. (2023). 7, 8-Dihydroxycoumarin derivatives: In silico molecular docking and in vitro anticholinesterase activity. Journal of Molecular Structure, 1274, 134535. (https://doi.org/10.1016/j.molstruc.2022.134535)
24. [24]. Mishra, S., Pandey, A., & Manvati, S. (2020). Coumarin: An emerging antiviral agent. Heliyon, 6(1). (https://doi.org/10.1016/j.heliyon.2020.e03217)
25. [25]. Qin, H. L., Zhang, Z. W., Ravindar, L., & Rakesh, K. P. (2020). Antibacterial activities with the structure-activity relationship of coumarin derivatives. European journal of medicinal chemistry, 207, 112832. (https://doi.org/10.1016/j.ejmech.2020.112832)
26. [26]. Ramsis, T. M., Ebrahim, M. A., & Fayed, E. A. (2023). Synthetic coumarin derivatives with anticoagulation and antiplatelet aggregation inhibitory effects. Medicinal Chemistry Research, 32(11), 2269-2278. (https://doi.org/10.1007/s00044-023-03148-1)
27. [27]. Todorov, L., Saso, L., & Kostova, I. (2023). Antioxidant activity of coumarins and their metal complexes. Pharmaceuticals, 16(5), 651. (https://doi.org/10.3390/ph16050651)
28. [28]. Çelik, E., Özdemir, M., Köksoy, B., Taskin‐Tok, T., Taslimi, P., Sadeghian, N., & Yalçın, B. (2023). New Coumarin− Thiosemicarbazone Based Zn (II), Ni (II) and Co (II) Metal Complexes: Investigation of Cholinesterase, α‐Amylase, and α‐Glucosidase Enzyme Activities, and Molecular Docking Studies. ChemistrySelect, 8(38), e202301786. (https://doi.org/10.1002/slct.202301786)
29. [29]. Rawat, A., & Reddy, A. V. B. (2022). Recent advances on anticancer activity of coumarin derivatives. European Journal of Medicinal Chemistry Reports, 5, 100038. (https://doi.org/10.1016/j.ejmcr.2022.100038)
30. [30]. Bisi, A., Cappadone, C., Rampa, A., Farruggia, G., Sargenti, A., Belluti, F., Di Martino, R. M. C., Malucelli, E., Meluzzi, A., Iotti, S., & Gobbi, S. (2017). Coumarin derivatives as potential antitumor agents: Growth inhibition, apoptosis induction and multidrug resistance reverting activity. European journal of medicinal chemistry, 127, 577-585. (https://doi.org/10.1016/j.ejmech.2017.01.020)
31. [31]. Çamur, M., Durmuş, M., & Bulut, M. (2012). Highly singlet oxygen generative water-soluble coumarin substituted zinc (II) phthalocyanine photosensitizers for photodynamic therapy. Polyhedron, 41(1), 92-103. (https://doi.org/10.1016/j.poly.2012.04.034)
32. [32]. Dandriyal, J., Singla, R., Kumar, M., & Jaitak, V. (2016). Recent developments of C-4 substituted coumarin derivatives as anticancer agents. European journal of medicinal chemistry, 119, 141-168. (https://doi.org/10.1016/j.ejmech.2016.03.087)
33. [33]. Roh, E. J. (2021). Inhibitory effects of coumarin derivatives on tyrosinase. Molecules, 26(8), 2346. (https://doi.org/10.3390/molecules26082346)
34. [34]. Deng, G., Xu, H., Kuang, L., He, C., Li, B., Yang, M., Zhang, X., Li, Z., & Liu, J. (2019). Novel nonlinear optical chromophores based on coumarin: Synthesis and properties studies. Optical Materials, 88, 218-222. (https://doi.org/10.1016/j.optmat.2018.11.035)
35. [35]. Liu, X., Cole, J. M., Waddell, P. G., Lin, T. C., Radia, J., & Zeidler, A. (2012). Molecular origins of optoelectronic properties in coumarin dyes: toward designer solar cell and laser applications. The Journal of Physical Chemistry A, 116(1), 727-737. (https://doi.org/10.1021/jp209925y)
36. [36]. Pradhan, R., Khandelwal, K., Shankar S, S., Panda, S. J., Purohit, C. S., Bag, B. P., Singhal, R., Liu, W., Zhu, X., Sharma, G. D., & Mishra, A. (2023). Correlation of Functional Coumarin Dye Structure with Molecular Packing and Organic Solar Cells Performance. Solar RRL, 7(21), 2300487. (https://doi.org/10.1002/solr.202300487)
37. [37]. Köksoy, B., Durmuş, M., & Bulut, M. (2015). Tetra-and octa-[4-(2-hydroxyethyl) phenoxy bearing novel metal-free and zinc (II) phthalocyanines: Synthesis, characterization and investigation of photophysicochemical properties. Journal of Luminescence, 161, 95-102. (https://doi.org/10.1016/j.jlumin.2014.12.044)
38. [38]. Zhou, X. Q., Meng, L. B., Huang, Q., Li, J., Zheng, K., Zhang, F. L., Liu, J. Y., & Xue, J. P. (2015). Synthesis and in vitro anticancer activity of zinc (II) phthalocyanines conjugated with coumarin derivatives for dual photodynamic and chemotherapy. ChemMedChem, 10(2), 304-311. (https://doi.org/10.1002/cmdc.201402401)
39. [39]. Boyar, C. Y., & Çamur, M. (2019). Novel water soluble 7-oxy-4-(pyridine-3-yl) coumarin substituted phthalocyanines as potential photosensitizers for photodynamic therapy. Inorganica Chimica Acta, 494, 30-41. (https://doi.org/10.1016/j.ica.2019.05.004)
40. [40]. J.G. Young, W. Onyebuagu, Synthesis and characterization of di-disubstituted phthalocyanines, The Journal of Organic Chemistry 55(7) (1990) 2155-2159. (https://doi.org/10.1021/jo00294a032)
41. [41]. George, R. D., & Snow, A. W. (1995). Synthesis of 3‐nitrophthalonitrile and tetra‐α‐substituted phthalocyanines. Journal of Heterocyclic Chemistry, 32(2), 495-498. (https://doi.org/10.1002/jhet.5570320219)
42. [42]. Dyrda, G. (2023). Photostability of indium phthalocyanines in organic solvents. (https://doi.org/10.21203/rs.3.rs-3407051/v1)
43. [43]. Gürel, E., Pişkin, M., Altun, S., Odabaş, Z., & Durmuş, M. (2015). Synthesis, characterization and investigation of the photophysical and photochemical properties of highly soluble novel metal-free, zinc (II), and indium (III) phthalocyanines substituted with 2, 3, 6-trimethylphenoxy moieties. Dalton Transactions, 44(13), 6202-6211. (https://doi.org/10.1039/C5DT00304K)
44. [44]. Özdemir, M., Karapınar, B., Yalçın, B., Salan, Ü., Durmuş, M., & Bulut, M. (2019). Synthesis and characterization of novel 7-oxy-3-ethyl-6-hexyl-4-methylcoumarin substituted metallo phthalocyanines and investigation of their photophysical and photochemical properties. Dalton Transactions, 48(34), 13046-13056. (https://doi.org/10.1039/C9DT02687H)
45. [45]. Güzel, E., Arslan, B. S., Atmaca, G. Y., Nebioğlu, M., & Erdoğmuş, A. (2019). High photosensitized singlet oxygen generating zinc and chloroindium phthalocyanines bearing (4‐isopropylbenzyl) oxy groups as potential agents for photophysicochemical applications. ChemistrySelect, 4(2), 515-520. (https://doi.org/10.1016/j.jphotochem.2015.10.026)
46. [46]. Yaşa Atmaca, G., & Erdoğmuş, A. (2017). Novel, Highly Soluble Non-Peripherally Phthalocyanines Bearing Bulky Groups Containing Fluorine Atoms: Synthesis, Characterization, Spectral and Improved Photophysicochemical Properties. Hacettepe Journal of Biology and Chemistry, 45(1). (10.15671/HJBC.2017.137)
47. [47]. Karapınar, B., Özdemir, M., Salan, Ü., Durmuş, M., Yalçın, B., & Bulut, M. (2019). 7‐Oxy‐3, 4‐cyclohexenecoumarin Carrying Novel Zinc (II) and Indium (III) Acetate Phthalocyanines: Synthesis, Characterization, Photophysical and Photochemical Properties. Chemistry Select, 4(33), 9632-9639. (https://doi.org/10.1002/slct.201902582