Synthesis, Crystal Structure, and Cytotoxicity Analysis of Dichloro-(2,2′:6′,2′′-Terpyridine)-Copper(Ⅱ)
Keywords:
Copper (II) complex, Crystal structure, Cytotoxicity, Cancer cells
Abstract
Malignant tumors, recognized as one of the most threatening diseases of the 20th century, continue to exhibit a rising incidence trend in the 21st century. Against this backdrop, metal complexes have attracted considerable attention due to their unique antitumor activities. In this study, we unexpectedly obtained a copper-based complex coordinated with 2,2':6',2''-Terpyridine and chloride anion ligands, and characterized its crystal structure using X-ray single-crystal diffraction technique. The cytotoxic effects of this metal complex against various tumor cell lines were evaluated through MTT assays, and the findings provide significant theoretical and practical foundations for developing novel anticancer drugs.
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[2] Krupa, K., Lesiów, M., Stokowa-Sołtys, K., Starosta, R., Ptaszyńska, N., Łęgowska, A., Rolka, K., Wernecki, M., Cal, M., & Jeżowska-Bojczuk, M. (2018). Copper(II) complexes with Fusobacterium nucleatum adhesin FadA: Coordination pattern, physicochemical properties and reactivity. Journal of Inorganic Biochemistry, 189, 69–80. https://doi.org/10.1016/j.jinorgbio.2018.09.012
[3] Wu, T., Wang, S., Lv, Y., Fu, T., Jiang, J., Lu, X., Yu, Z., Zhang, J., Wang, L., & Zhou, H. (2022). A new bis(thioether)-dipyrrin N2S2 ligand and its coordination behaviors to nickel, copper and zinc. Dalton Transactions, 51(25), 9699–9707. https://doi.org/10.1039/d2dt01282k
[4] Krasnovskaya, O., Naumov, A., Guk, D., Gorelkin, P., Erofeev, A., Beloglazkina, E., & Majouga, A. (2020). Copper coordination compounds as biologically active agents. International Journal of Molecular Sciences, 21(11), 3965. https://doi.org/10.3390/ijms21113965
[5] Fan, L., Tian, M., Liu, Y., Deng, Y., Liao, Z., & Xu, J. (2017). Salicylate•phenanthroline copper(II) complex induces apoptosis in triple-negative breast cancer cells. Oncotarget, 8(18), 29823–29832. https://doi.org/10.18632/oncotarget.15961
[6] Fan, R., Wei, J. C., Xu, B. B., Jin, N., Gong, X. Y., & Qin, X. Y. (2023). A novel chiral oxazoline copper(II)-based complex inhibits ovarian cancer growth in vitro and in vivo by regulating VEGF/VEGFR2 downstream signaling pathways and apoptosis factors. Dalton Transactions, 52(33), 11427–11440. https://doi.org/10.1039/d3dt01648j
[7] Hou, X. X., Ren, Y. P., Luo, Z. H., Jiang, B. L., Lu, T. T., Huang, F. P., & Qin, X. Y. (2021). Two novel chiral tetranucleate copper-based complexes: Syntheses, crystal structures, inhibition of angiogenesis and the growth of human breast cancer in vitro and in vivo. Dalton Transactions, 50(41), 14684–14694. https://doi.org/10.1039/d1dt02033a
[8] Xu, B. B., Jin, N., Liu, J. C., Liao, A. Q., Lin, H. Y., & Qin, X. Y. (2024). Arene-arene coupled disulfamethazines (or sulfadiazine)-phenanthroline-metal(II) complexes were synthesized by in situ reactions and inhibited the growth and development of triple-negative breast cancer through the synergistic effect of antiangiogenesis, anti-inflammation, pro-apoptosis, and cuproptosis. Journal of Medicinal Chemistry, 67(9), 7088–7111. https://doi.org/10.1021/acs.jmedchem.3c02432
[9] Liao, A. Q., Wen, J., Wei, J. C., Xu, B. B., Jin, N., Lin, H. Y., & Qin, X. Y. (2024). Syntheses, crystal structures of copper(II)-based complexes of sulfonamide derivatives and their anticancer effects through the synergistic effect of anti-angiogenesis, anti-inflammation, pro-apoptosis and cuproptosis. European Journal of Medicinal Chemistry, 280, 116954. https://doi.org/10.1016/j.ejmech.2024.116954
[10] Ziesak, A., Wesp, T., Hübner, O., Kaifer, E., Wadepohl, H., & Himmel, H. J. (2015). Counter-ligand control of the electronic structure in dinuclear copper-tetrakisguanidine complexes. Dalton Transactions, 44(44), 19111–19125. https://doi.org/10.1039/c5dt03270a
[11] Tsang, T., Davis, C. I., & Brady, D. C. (2021). Copper biology. Current Biology, 31(9), R421–R427. https://doi.org/10.1016/j.cub.2021.03.054
[12] Hussain, A., AlAjmi, M. F., Rehman, M. T., Amir, S., Husain, F. M., Alsalme, A., Siddiqui, M. A., AlKhedhairy, A. A., & Khan, R. A. (2019). Copper(II) complexes as potential anticancer and nonsteroidal anti-inflammatory agents: In vitro and in vivo studies. Scientific Reports, 9, 1–17. https://doi.org/10.1038/s41598-019-41063-x
[13] Wilcken, R., Zimmermann, M. O., Lange, A., Joerger, A. C., & Boeckler, F. M. (2013). Principles and applications of halogen bonding in medicinal chemistry and chemical biology. Journal of Medicinal Chemistry, 56(4), 1363–1388. https://doi.org/10.1021/jm3012068
[14] Tulchinsky, Y., Hendon, C. H., Lomachenko, K. A., Borfecchia, E., Melot, B. C., Hudson, M. R., Tarver, J. D., Korzyński, M. D., Stubbs, A. W., Kagan, J. J., Lamberti, C., Brown, C. M., & Dincă, M. (2017). Reversible capture and release of Cl₂ and Br₂ with a redox-active metal-organic framework. Journal of the American Chemical Society, 139(16), 5992–5997. https://doi.org/10.1021/jacs.7b02161
[15] Bickerton, L. E., Docker, A., Sterling, A. J., Kuhn, H., Duarte, F., Beer, P. D., & Langton, M. J. (2021). Highly active halogen bonding and chalcogen bonding chloride transporters with non-protonophoric activity. Chemistry – A European Journal, 27(45), 11738–11745. https://doi.org/10.1002/chem.202101681
[16] Jentzsch, A. V., & Matile, S. (2015). Anion transport with halogen bonds. Topics in Current Chemistry, 358, 205–239. https://doi.org/10.1007/128_2014_541
[17] Wei, Q., Ge, B. D., Zhang, J., Sun, A. H., Li, J. H., Han, S. D., & Wang, G. M. (2019). Tripyridine-derivative-derived semiconducting iodo-argentate/cuprate hybrids with excellent visible-light-induced photocatalytic performance. Chemistry – An Asian Journal, 14(2), 269–277. https://doi.org/10.1002/asia.201801555
[18] Kodera, M., Kajita, Y., Tachi, Y., & Kano, K. (2003). Structural modulation of Cu(I) and Cu(II) complexes of sterically hindered tripyridine ligands by the bridgehead alkyl groups. Inorganic Chemistry, 42(4), 1193–1203. https://doi.org/10.1021/ic026008m
[19] Dorofeeva, V. N., Pavlishchuk, A. V., Kiskin, M. A., Efimov, N. N., Minin, V. V., Lytvynenko, A. S., Gavrilenko, K. S., Kolotilov, S. V., Novotortsev, V. M., & Eremenko, I. L. (2019). Co(II) complexes with a tripyridine ligand, containing a 2,6-di-tert-butylphenolic fragment: Synthesis, structure, and formation of stable radicals. ACS Omega, 4(1), 203–213. https://doi.org/10.1021/acsomega.8b02595
[20] Suntharalingam, K., White, A. J., & Vilar, R. (2009). Synthesis, structural characterization, and quadruplex DNA binding studies of platinum(II)-terpyridine complexes. Inorganic Chemistry, 48(19), 9427–9435. https://doi.org/10.1021/ic901319n
[21] Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K., & Puschmann, H. (2009). OLEX2: A complete structure solution, refinement and analysis program. Journal of Applied Crystallography, 42(2), 339–341. https://doi.org/10.1107/S0021889808042726
[22] Sheldrick, G. M. (2015). Crystal structure refinement with SHELXL. Acta Crystallographica Section C: Structural Chemistry, 71(1), 3–8. https://doi.org/10.1107/S2053229614024218
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2025-04-30
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