Abstract
Phthalocyanines (Pcs) have the potential to be used in many medical applications. Novel Zn (II), Co (II), and Cu (II) phthalocyanines (Pcs) 4, 5, and 6, respectively, containing four methylpropiophenonyl units at the peripheral positions were described. Pcs were synthesized by cyclotetramerization of the previously prepared precursor 2-hydroxy-4'-[2-(3,4-dicyanophenoxyethoxy)]-2-methylpropiophenone 3 with the presence of metal salts under nitrogen atmosphere. The compounds were characterized by elemental analysis, IR (Infrared spectroscopy), UV–visible spectroscopy, and Laser Desorption ionization time-of-flight mass spectroscopy (LDI-TOF–MS) methods. The compounds were tested for in vitro cytotoxicity in cultured human cells, and thermotolerance in Caenorhabditis elegans (C. elegans). Standard MTT assays were carried out for cytotoxicity testing using HeLa and L929 cells. Results showed that there was no significant decrease in the cell viability with zinc (II), cobalt (II), and copper (II) phthalocyanines (ZnPc, CoPc, and CuPc) at 0.25 μM concentration. C. elegans survival assay with ZnPc, CoPc, and CuPc under heat stress showed that although a dose-dependent statistically significant toxicity was observed for ZnPc and CuPc, CoPc was not toxic at all concentrations tested and even increased the survival of worms at the 0.050–0.250 µM concentration range. Therefore, CoPc can be a lead compound for further preclinical studies for its potential in photodynamic therapy (PDT) and anti-aging purposes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aktaş A, Akyüz D, Koca A, Acar İ (2018) Synthesis and investigation of spectroelectrochemical properties of peripherally tetra-substituted phthalocyanine bearing 3-(4-{[3-(trifluoromethyl) benzyl] oxy} phenyl) propan-1-ol and its metallo compounds. J Incl Phenom Macrocycl Chem 92(1):223–235
Antebi A (2007) Genetics of aging in caenorhabditis elegans. PLoS Genet 3(9):1565–2157
Aziz T, Sun Y, Wu ZH, Haider M, Qu TY, Khan A, Sun DM (2021) A flexible nickel phthalocyanine resistive random-access memory with multi-level data storage capability. J Mater Sci Technol 86:151–157. https://doi.org/10.1016/j.jmst.2021.02.008
Bal Öztürk A, Cevher E, Pabuccuoğlu S, Özgümüş S (2019) pH sensitive functionalized hyperbranched polyester based nanoparticulate system for the receptor-mediated targeted cancer therapy. Int J Polym 68:417–432. https://doi.org/10.1080/00914037.2018.1452226
Başak AS, Özkaya AR, Altındal A, Salih B, Şengül A, Bekaroğlu Ö (2014) Synthesis, characterization, oxygen electrocatalysis and OFET properties of novel mono-and ball-type metallophthalocyanines. Dalton Trans 43:5858–5870. https://doi.org/10.1039/C3DT51955D
Benedetto A, Bambade T, Au C, Tullet JM, Monkhouse J, Dang H, Gems D (2019) New label-free automated survival assays reveal unexpected stress resistance patterns during C. J Investig Dermatol Symp Proc 18:e12998. https://doi.org/10.1038/jidsymp.1998.3
Ben-Hur E, Carmichael A, Riesz P, Rosenthal I (1985) Photochemical generation of superoxide radical and the cytotoxicity of phthalocyanines. Int J Radiat biol Rela. Stud Phys Chem Med 48:837–846. https://doi.org/10.1080/09553008514551931
Çakır D, Göksel M, Çakır V, Durmuş M, Biyiklioglu Z, Kantekin H (2015) Amphiphilic zinc phthalocyanine photosensitizers: synthesis, photophysicochemical properties and in vitro studies for photodynamic therapy. Dalton Trans 44:9646–9658. https://doi.org/10.1039/C5DT00747J
Ceyhan T, Altındal A, Özkaya AR, Salih B, Bekaroğlu Ö (2010) Novel ball-type four dithioerythritol bridged metallophthalocyanines and their water-soluble derivatives: Synthesis and characterization, and electrochemical, electrocatalytic, electrical, and gas sensing properties. Dalton Dalton Trans 39:9801–9814. https://doi.org/10.1039/c0dt00641f
Değirmencioğlu İ, Atalay E, Er M, Köysal Y, Işık Ş, Serbest K (2010) Novel phthalocyanines containing substituted salicyclic hydrazone-1, 3-thiazole moieties: Microwave-assisted synthesis, spectroscopic characterization, X-ray structure and thermal characterization. Dyes Pigm 84:69–78. https://doi.org/10.1016/j.dyepig.2009.07.001
Farajzadeh N, Karaoğlu HP, Akin M, Saki N, Koçak MB (2019) Synthesis, Photophysical and biological properties of new phthalocyanines bearing peripherally 4-(Trifluoromethoxy) phenoxy groups. Chem Sel 4:8998–9005. https://doi.org/10.1002/slct.201901509
Gordon J, Lithgow TMW, Hinerfeld DA, Thomas EJ (2011) Thermotolerance of a long-lived mutant of caenorhabditis elegans. J Gerontol 49:270–276. https://doi.org/10.1093/geronj/49.6.b270
Greenwald I, Kovall R (2018) Notch signaling: genetics and structure. Wormbook Online Rev C. Elegans Biol [Internet]
Han SK, Lee D, Lee H, Kim D, Son HG, Yang JS, Kim S (2016) OASIS 2: online application for survival analysis 2 with features for the analysis of maximal lifespan and healthspan in aging research. Oncotarget 7:56147
Herndon LA, Wolkow CA, Driscoll M, Hall DH (2017) Effects of ageing on the basic biology and anatomy of C elegans. In: Anders O, Matthew S (eds) Ageing: lessons from C elegans. Springer, Cham, pp 9–39
Hori Y, Murata A, Kikuchi K, Suzuki S (1987) Electrochemical reduction of carbon dioxides to carbon monoxide at a gold electrode in aqueous potassium hydrogen carbonate. J Chem Soc Chem Comm 10:728–729. https://doi.org/10.1039/C39870000728
Kakı E, Gögsu N, Altındal A, Salih B, Bekaroǧlu Ö (2019) Synthesis, characterization, and VOCs adsorption kinetics of diethylstilbestrol-substituted metallophthalocyanines. Porphyr Sci Women 3:991–999
Kandaz M, Yılmaz İ, Bekaroğlu Ö (2000) Synthesis and characterization of novel symmetrical phthalocyanines substituted with mono-or bi-macrocycles. Polyhedron 19:115–121. https://doi.org/10.1016/S0277-5387(99)00344-7
Keith SA, Amrit FRG, Ratnappan R, Ghazi A (2014) The C. elegans healthspan and stress-resistance assay toolkit. Method 68:476–486. https://doi.org/10.1016/j.ymeth.2014.04.003
Kluson P, Drobek M, Kalaji A, Zarubova S, Krysa J, Rakusan J (2008) Singlet oxygen photogeneration efficiencies of a series of phthalocyanines in well-defined spectral regions. A J Photoch Photobio 199:267–273. https://doi.org/10.1016/j.jphotochem.2008.06.003
Koray AR, Ahsen V, Bekâroǧlu Ö (1986) Preparation of a novel, soluble copper phthalocyanine with crown ether moieties. J Chem Soc Chem Comm 12:932–933. https://doi.org/10.1039/C39860000932
Kulaç D, Bulut M, Altındal A, Özkaya AR, Salih B, Bekaroğlu Ö (2007) Synthesis and characterization of nov, el 4-nitro-2-(octyloxy) phenoxy substituted symmetrical and unsymmetrical Zn (II), Co (II) and Lu (III) phthalocyanines. Polyhedron 26:5432–5440. https://doi.org/10.1016/j.poly.2007.08.015
Leznoff C, Lever A (1989) Properties and Applications. VCH New York. https://doi.org/10.1002/adma.19930051217
Li X, Jeon YH, Kwon N et al (2021) In Vivo-assembled phthalocyanine/albumin supramolecular complexes combined with a hypoxia-activated prodrug for enhanced photodynamic immunotherapy of cancer. Biomaterials 266:120430. https://doi.org/10.1016/j.biomaterials.2020.120430
Lin AL, Fan PP, Liu SF et al (2020) A phthalocyanine-based liposomal nanophotosensitizer with highly efficient tumor-targeting and photodynamic activity. Dyes Pigm 180:108455. https://doi.org/10.1016/j.dyepig.2020.108455
Lithgow GJ, White TM, Melov S, Johnson TE (1995) Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci 92:7540–7544. https://doi.org/10.1073/pnas.92.16.7540
Liu W, Jensen TJ, Fronczek FR et al (2005) Synthesis and cellular studies of nonaggregated water-soluble phthalocyanines. J Med Chem 48:1033–1041. https://doi.org/10.1021/jm049375b
Liu Q, Pang M, Tan S, Wang J, Chen Q, Wang K, Hong Z (2018) Potent peptide-conjugated silicon phthalocyanines for tumor photodynamic therapy. J Cancer 9:310–320. https://doi.org/10.7150/jca.22362
Malenov DP, Janjić GV, Medaković VB, Hall MB, Zarić SD (2017) Noncovalent bonding: Stacking interactions of chelate rings of transition metal complexes. Coord Chem Rev 345:318–341. https://doi.org/10.1016/j.ccr.2016.12.020
Malenov DP, Zarić SD (2019) Strong stacking interactions of metal–chelate rings are caused by substantial electrostatic component. Dalton Trans 48(19):6328–6332
Özçeşmeci M, Sancar-Baş S, Akkurt B, Hamuryudan E, Bolkent Ş (2018) Synthesis and biological uses of a3b type water-soluble phthalocyanine alternate to alcian blue. Chem Sel 3:12805–12812. https://doi.org/10.1002/slct.201803371
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 Trans 48:13046–13056. https://doi.org/10.1039/C9DT02687H
Ozdemir M, Artuc GO, Guler EM et al (2021) Phthalocyanines bearing silazane group for colorectal cancer. Dyes Pigm 196:1–12. https://doi.org/10.1016/j.dyepig.2021.109832
Prabhu CPK, Nemakal M, Managa M, Nyokong T, Koodlur Sannegowda L (2021) Symmetrically substituted Zn and Al phthalocyanines and polymers for photodynamic therapy application. Front Chem 9:452. https://doi.org/10.3389/fchem.2021.647331
Rella R, Spadavecchia J, Ciccarella G, Siciliano P, Vasapollo G, Valli L (2003) Optochemical vapour detection using spin coated thin films of metal substituted phthalocyanines. Sens Actuator B Chem 89:86–91. https://doi.org/10.1016/S0925-4005(02)00447-1
Rosenthal I (1991) Phthalocyanines as photodynamic sensitizers. Photochem Photobiol 53:859–870. https://doi.org/10.1111/j.1751-1097.1991.tb09900.x
Şener S, Bayraç TA, Şener BB, Tozlu C, Acar N, Salih B, Yüksel M, Bekaroğlu Ö (2019) Synthesis, characterization, and DFT study of novel metallo phtalocyanines with four carboranyl clusters as photosensitisers for the photodynamic therapy of breast cancer cells. Eur J Pharm Sci 129:124–131. https://doi.org/10.1016/j.ejps.2018.12.017
Şenoğlu S, Özer M, Dumludağ F, Acar N, Salih B, Bekaroğlu Ö (2020) Synthesis, characterization, DFT study, conductivity, and effects of humidity on CO2 sensing properties of the novel tetrakis-[2-(dibenzylamino) ethoxyl] substituted metallophthalocyanines. Sens Actuator B Chem 310:127860. https://doi.org/10.1016/j.snb.2020.1278607
Seoudi R, EI-Bahy GS, EI-Sayed ZA (2005) FTIR, TGA and DC electrical conductivity studies of phthalocyanine and its complexes. J Mol Struct 753(1–3):119–126. https://doi.org/10.1016/j.molstruc.2005.06.003
Sevim AM, Arıkan S, Koca A, Gül A (2012) Synthesis and spectroelectrochemistry of new phthalocyanines with ester functionalities. Dyes Pigm 92:1114–1121. https://doi.org/10.1016/j.dyepig.2011.07.015
Walker GA, Walker DW, Lithgow GJ. (1998). A relationship between thermotolerance and longevity in caenorhabditis elegans. In: Journal of investigative dermatology symposium proceedings. 3:6–10
Wightman B (2015) A Transparent window into biology: a primer on caenorhabditis elegans 3: 6–10. http://www.wormbook.org/
Yang JS, Nam HJ, Seo M, Han SK, Choi Y, Nam HG, Kim S (2011) OASIS: online application for the survival analysis of lifespan assays performed in aging research. PLoS One 6:e23525. https://doi.org/10.1371/journal.pone.0023525
Yavuz Dokgöz E, Tengirsek E, Güleç M, Akgüner ZP, Erol T, Emik S, Olgun A (2019) Turkish. J Biochem. https://doi.org/10.1515/tjb-2019-frontmatter44s2
Yelten A, Karal-Yılmaz O, Akguner ZP, Ayça BO,Yilmaz S (2020) In-vitro bioactivity investigation of sol-gel derived alumina-bovine hydroxyapatite (Bha) composite powders. Gazi Univ J Sci 33: 690-700. https://doi.org/10.35378/gujs.541345
Zawadzka A, Płóciennik P, Strzelecki J, Pranaitis M, Dabos-Seignon S, Sahraoui B (2013) Structural and nonlinear optical properties of as-grown and annealed metallophthalocyanine thin films. Thin Solid Films 545:429–437. https://doi.org/10.1016/j.tsf.2013.07.042
Zhuang Z, Lv T, Li M, Zhang Y, Xue T, Yang L, Zhang W (2014) The lifespan-extending effects of Nymphaea hybrid root extract in the nematode caenorhabditis elegans. Plant Food Hum Nutr 69(4):304–309
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Şenoğlu, S., Güleç, M., Dokgöz, E.Y. et al. Synthesis, characterization, in vitro cytotoxicity of novel metallo phthalocyanines with four methylpropiophenonyl clusters and their effects on Caenorhabditis elegans thermotolerance. Chem. Pap. 77, 1561–1572 (2023). https://doi.org/10.1007/s11696-022-02415-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11696-022-02415-6