THREE NEW BIS(ACYLHYDRAZONE) MONONUCLEAR TRANSITION METAL COMPLEXES: SYNTHESIS, CHARACTERIZATIONS AND DNA INTERACTION STUDIES

Öz

In recent years, studies on the design and synthesis of artificial nucleases with biological, structural and coordination properties have been increasing. With this study, mononuclear complex compounds were obtained with Cu(II), Ni(II) and Zn(II) transition metal ion salts of bis(acylhydrazone) ligand, which has the potential to show biological activity and has revolving atoms such as N and O in its structure. The characteristic structures of the obtained complex compounds were elucidated using various techniques such as FTIR, UV-Visible, 1H-NMR, TGA, elemental analysis and magnetic susceptibility. The DNA-binding activities of potential artificial metallonucleases, whose structures were elucidated, were investigated using the UV-visible absorption titration method. Additionally, their DNA-cleavge activities were analyzed using the agarose gel electrophoresis method. The DNA binding mode and cleavage mechanisms were determined as part of this study.. In line with the results obtained, it was determined that the binding mode between DNA and the complexes is a noncovalent interaction. It has been demonstrated that the compounds cleavage DNA both oxidatively and hydrolytically. It has been revealed that the radicals involved in DNA cleavage activity are H2O2, superoxide and hydroxyl radicals. It was revealed that the compound with the highest cleavage and bonding interaction was the Cu(II) complex, followed by Ni(II) and Zn(II) complexes.

Anahtar Kelimeler

• bis(acylhydrazones)
• metal complexes
• DNA interactions

ÜÇ YENİ BİS(AÇİLHİDRAZON) MONONÜKLEER GEÇIŞ METALI KOMPLEKSİ: SENTEZ, KARAKTERİZASYON VE DNA ETKİLEŞİM ÇALIŞMALARI

Öz

Son yıllarda biyolojik açıdan aktif ve yapısında metal içeren yapay nükleazların tasarlanması ve sentezine yönelik çalışmalara giderek çoğalmaktadır. Gerçekleştirilen bu çalışma ile biyolojik aktivite gösterme potansiyeli olan ve yapısında N ve O gibi dönor atomlar bulunduran bis(açilhidrazon)ligandın Cu(II), Ni(II) ve Zn(II) geçiş metal iyon tuzlarıyla mononükleer kompleks bileşikleri elde edilmiştir. Elde edilen kompleks bileşiklerin karakteristik yapıları, FTIR, UV-Görünür, 1H-NMR, TGA, elemental analiz ve magnetic süssebilite gibi çeşitli teknikler kullanılarak aydınlatılmıştır. Yapıları aydınlatılan potansiyel yapay metallonükleazların UV-vis. adsorbsiyon titrasyon metodu ile DNA-bağlanma, agaroz jel elektroforez yöntemi ile de DNA-kesme aktiviteleri incelenmiştir. DNA bağlanma modu ve kesme mekanizmaları belirlenmiştir. Elde edilen sonuçlar doğrultusunda, DNA ile kompleksler arasındaki bağlanma modunun nonkovalent bir etkileşim olduğu belirlenmiştir. Bileşiklerin hem oksidadif hem de hidrolitik olarak DNA’ yı kestiği ortaya koyulmuştur. DNA kesme aktivitesinde rol alan radikallerin H2O2, superoksit ve hidroksil radikalleri olduğu ortaya çıkarılmıştır. Kesme ve bağlanma etkileşiminin en yüksek olduğu bileşiğin Cu(II) kompleksi olduğu ve bu sıralamayı Ni(II) ve Zn(II) komplekslerinin izlediği ortaya konmuştur.

Anahtar Kelimeler

• bis(açilhidrazon)lar
• metal kompleksler
• DNA etkileşim

Kaynakça

1. Lin, Y. Q., He, S. X., Tian, X. M., Huang, C., Chen, D. M. and Zhu, B. X., ‘’Synthesis, crystal structures and antibacterial properties of four complexes derived from mono-or diquinoline-substituted acylhydrazone ligands’’, Inorganica Chimica Acta, 541, 121080, 2022.
2. Zhang, Q., Jiang, F., Huang, Y., Wu, M. and Hong, M., ‘’Coordination-driven face-directed self-assembly of a M9L6 hexahedral nanocage from octahedral Ni (II) ions and asymmetric hydrazone ligands’’, Crystal Growth and Design, 9(1), 28-31, 2009.
3. Ye, X. P., Zhu, T. F., Wu, W. N., Ma, T. L., Xu, J., Zhang, Z. P. and Jia, L., ‘’Syntheses, characterizations and biological activities of two Cu (II) complexes with acylhydrazone ligand bearing pyrrole unit’’, Inorganic Chemistry Communications, 47, 60-62, 2014.
4. Badiger, D. S., Hunoor, R. S., Patil, B. R., Vadavi, R. S., Mangannavar, C. V., Muchchandi, I. S. and Gudasi, K. B., ‘’Synthesis, spectroscopic properties and biological evaluation of transition metal complexes of salicylhydrazone of anthranilhydrazide: X-ray crystal structure of copper complex’’, Inorganica chimica acta, 384, 197-203, 2012.
5. Dash, S. P., Panda, A. K., Pasayat, S., Dinda, R., Biswas, A., Tiekink, E. R. and Sinn, E., ‘’Oxidovanadium (v) complexes of Aroylhydrazones incorporating heterocycles: Synthesis, characterization and study of DNA binding, photo-induced DNA cleavage and cytotoxic activities’’, RSC Advances, 5(64), 51852-51867, 2015.
6. Chang, H. Q., Jia, L., Xu, J., Xu, Z. Q., Chen, R. H., Wu, W. N. and Wang, Y., ‘’Syntheses, characterizations, antitumor activities and cell apoptosis induction of Cu (II), Zn (II) and Cd (II) complexes with hydrazone Schiff base derived from isonicotinohydrazide’’, Inorganic Chemistry Communications, 57, 8-10, 2015.
7. Santiago, P. H., Santiago, M. B., Martins, C. H. and Gatto, C. C., ‘’Copper (II) and zinc (II) complexes with Hydrazone: Synthesis, crystal structure, Hirshfeld surface and antibacterial activity’’, Inorganica Chimica Acta, 508, 119632, 2020.
8. Xu, J., Zhou, T., Xu, Z. Q., Gu, X. N., Wu, W. N., Chen, H. and Chen, R. H., ‘’Synthesis, crystal structures and antitumor activities of copper (II) complexes with a 2-acetylpyrazine isonicotinoyl hydrazone ligand’’, Journal of Molecular Structure, 1128, 448-454, 2017.

9. Rocha, C. S., Bomfim Filho, L. F., de Souza, A. E., Diniz, R., Denadai, A. M., Beraldo, H. and Teixeira, L. R., ‘’Structural studies and investigation on the antifungal activity of silver (I) complexes with 5-nitrofuran-derivedhydrazones’’, Polyhedron, 170, 723-730, 2019.
10. Yang, Q. Y., Cao, Q. Q., Qin, Q. P., Deng, C. X., Liang, H. and Chen, Z. F., ‘’Syntheses, Crystal Structures, and Antitumor Activities of Copper (II) and Nickel (II) Complexes with 2-((2-(Pyridin-2-yl) hydrazono) methyl) quinolin-8-ol’’, International Journal of Molecular Sciences, 19(7), 1874, 2018.
11. Giziroglu, E., Aygün, M., Sarikurkcu, C., Kazar, D., Orhan, N., Firinci, E. and Gokcen, C., ‘’Synthesis, characterization and antioxidant activity of new dibasic tridentate ligands: X-ray crystal structures of DMSO adducts of 1, 3-dimethyl-5-acetyl-barbituric acid o-hydroxybenzoyl hydrazone copper (II) complex’’, Inorganic Chemistry Communications, 36, 199-205, 2013.
12. Parrilha, G. L., Vieira, R. P., Rebolledo, A. P., Mendes, I. C., Lima, L. M., Barreiro, E. J. and Beraldo, H., ‘’Binuclear zinc (II) complexes with the anti-inflammatory compounds salicylaldehyde semicarbazone and salicylaldehyde-4-chlorobenzoyl hydrazone (H2LASSBio-1064)’’, Polyhedron, 30(11), 1891-1898, 2011.
13. Tirkey, V., Mishra, S., Dash, H. R., Das, S., Nayak, B. P., Mobin, S. M. and Chatterjee, S.,’’ Synthesis, characterization and antibacterial studies of ferrocenyl and cymantrenyl hydrazone compounds’’, Journal of Organometallic Chemistry, 732, 122-129, 2013.
14. Santini, C., Pellei, M., Gandin, V., Porchia, M., Tisato, F. and Marzano, C., ‘’Advances in copper complexes as anticancer agents’’, Chemical reviews, 114(1), 815-862, 2014.
15. Gökçe, C. and Gup, R., ‘’Synthesis, characterization and DNA interaction of new copper (II) complexes of Schiff base-aroylhydrazones bearing naphthalene ring’’ Journal of Photochemistry and Photobiology B: Biology, 122, 15-23, 2013.
16. Tardito, S., Bassanetti, I., Bignardi, C., Elviri, L., Tegoni, M., Mucchino, C. and Marchio, L., ‘’Copper binding agents acting as copper ionophores lead to caspase inhibition and paraptotic cell death in human cancer cells’’ Journal of the American Chemical Society, 133(16), 6235-6242, 2011.
17. Jamal, R. A., Ashiq, U., Arshad, M. N., Maqsooda, Z. T. and Khanb, I. U., “4-Hydroxybenzohydrazide”, Acta Crystallographica Section E, E65, 1764, 2009.
18. Gup, R., Gökçe, C. and Dilek, N., ‘’Seven-coordinated cobalt (II) complexes with 2, 6-diacetylpyridine bis (4-hydroxybenzoylhydrazone): synthesis, characterisation, DNA binding and cleavage properties’’, Supramolecular Chemistry, 27(10), 629-641, 2015.
19. Gökçe, C. and Gup, R., ‘’Copper (II) complexes of acylhydrazones: synthesis, characterization and DNA interaction’’, Applied Organometallic Chemistry, 27(5), 263-268, 2013.
20. Chandra, S. and Sharma, A. M., “Nickel(II) and copper(II) complexes with Schiff base ligand 2,6-diacetylpyridine bis(carbohydrazone): Synthesis and IR, mass, 1H NMR, electronic and EPR spectral studies”, Spectrochimica Acta Part A, 72, 851-857, 2009.
21. Güp, R., Gökçe, C. and Dilek, N., ‘’Synthesis, structural characterization and DNA interaction of zinc complex from 2, 6-diacetylpyridine dihydrazone and {4-[(2E)-2-(hydroxyimino) acetyl] phenoxy} acetic acid’’, Journal of Photochemistry and Photobiology B: Biology, 144, 42-50, 2015.
22. López, A. T., Luckie, M. R. A., Otero, D. M., Mendieta, V. S., Escudero, R. and Morales, F., ‘’Two-Dimensional Copper Coordination Polymer Assembled with Fumarate and 5, 5’-Dimethyl-2, 2’-bipyridine: Synthesis, Crystal Structure and Magnetic Properties’’, Journal of Chemical Crystallography, 1-8, 2022.
23. Schleife, F., Rodenstein, A. and Kirmse, R., Kersting, B., “Seven-coordinate Mn(II) and Co(II) complexes of the pentadentate ligand 2,6-diacetyl-4-carboxymethyl-pyridine bis(benzoylhydrazone): Synthesis, crystal structure and magnetic properties”, Inorganica Chimica Acta, 374, 521-527, 2011.
24. Gökce, C. and Gup, R., ‘’Synthesis and characterisation of Cu (II), Ni (II), and Zn (II) complexes of furfural derived from aroylhydrazones bearing aliphatic groups and their interactions with DNA’’, Chemical Papers, 67(10), 1293-1303, 2013.
25. Popov, L. D., Shcherbakov, I. N., Levchenkov, S. I., Tupolova, Y. P., Kogan, V. A. and Lukov, V. V., “Binuclear copper(II) and oxovanadium(IV) complexes with 2,6-diformyl-4-tert-butylphenol-bis-(1’ phthalazinylhydrazone). Synthesis, properties and quantum chemical study”, Journal of Coordination Chemistry, 61(3), 392-409, 2008.
26. Gök, Y. and Bek [acaron] roglu, Ö., ‘’The Synthesis and Complex Formatirn of Stererisomers of some new α-Dioximes’’, Synthesis and Reactivity in Inorganic and Metal-Organic Chemistry, 11(7), 621-631, 1981.
27. Gup, R. and Kırkan, B., ‘’Synthesis and spectroscopic studies of copper (II) and nickel (II) complexes containing hydrazonic ligands and heterocyclic coligand’’, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 62(4-5), 1188-1195, 2005.
28. Gup, R. and Kırkan, B., ‘’Synthesis and spectroscopic studies of mixed-ligand and polymeric dinuclear transition metal complexes with bis-acylhydrazone tetradentate ligands and 1, 10-phenanthroline’’, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 64(3), 809-815, 2006.
29. Mohanraj, M., Ayyannan, G., Raja, G., and Jayabalakrishnan, C., ‘’Synthesis, characterization and in vitro biological assays of copper (II) and nickel (II) complexes with furan‐2‐carboxylic acid hydrazide’’, Applied Organometallic Chemistry, 31(4), e3582, 2017.
30. Sirajuddin, M., Ali, S. and Badshah, A., ‘’Drug–DNA interactions and their study by UV–Visible, fluorescence spectroscopies and cyclic voltametry’’, Journal of Photochemistry and Photobiology B: Biology, 124, 1-19, 2013.