New pyrazolone-based Schiff base Cu(II) complexes: Synthesis, spectra, theoretical calculation and protein binding

Document Type : Original Article

Authors

Department of Chemistry, Faculty of Science, Semnan University, Semnan, Iran

Abstract

In this study, five Schiff base ligands of the NO type were synthesized through the condensation of 4-aminoantipyrine with different aldehydes. These aldehydes include 3,5-dibromo-2-hydroxybenzaldehyde (HL1), 3,5-dichloro-2-hydroxybenzaldehyde (HL2), 3,5-diiodo-2-hydroxybenzaldehyde (HL3), 3-ethoxy-2- hydroxybenzaldehyde (HL4) and 2-hydroxy-1- naphtaldehyde (HL5). Copper(II) complexes were then prepared using these ligands. The synthesized complexes were characterized using various spectroscopic techniques such as spectrometry, IR, UV-Vis, and electrochemical (CV) methods. Elemental analysis was also performed to determine the elemental composition of the complexes. To gain further insight into the structural features and properties of the complexes, computational methods were employed. The optimization of the complex structures was carried out using Gaussian 09 software with the B3LYP 6-311G basis set. This allowed for the determination of important physical characteristics of the complexes. Frequency calculations were performed to obtain vibrational frequencies, while UV-Vis calculations were carried out to explain the electronic absorption spectra of the complexes. The experimental results obtained from the various spectroscopic techniques were compared with the theoretical results obtained from the computational studies. Theoretical exploration of the frontier molecular orbitals and energy gaps of the complexes provided insight into their electronic structures and stability. Furthermore, molecular docking studies were conducted to investigate the binding affinity of the tested complexes towards STAT3. The Protein Data Bank (PDB) entry 1bg1 was used as the target protein. By analyzing the docking results and summarizing the interactions during the binding process, the complexes exhibited potential effectiveness as inhibitors against colon cancer. Metal complexes (1-5) showed that they may be used as new drug candidates for colon cancer. The molecular binding of copper complexes compared to Crizotinib, and niclosamide (as a drug) showed that they have a better performance and are completely placed in the active site of the receptor. So, the present study gives a new insight for in vivo investigation of the complexes.

Keywords

Main Subjects

This is an open access article under the CC-BY-SA 4.0 license.( https://creativecommons.org/licenses/by-sa/4.0/)

References

[1] Karrouchi, K., Radi, S., Ramli, Y., Taoufik, J., Mabkhot, Y. N., Al-Aizari, F. A., & Ansar, M. H., (2018). Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review. Molecules., 23(1), 134. ‏
[2] Ghasemi, L., Behzad, M., Gharib, A., Arab, A., & Abbasi, A., (2023). A pyrazolone-based dinuclear Cu(II) Schiff-base complex: DFT studies on the rate-determining steps of the tautomerism in the ligand and molecular docking modelling with COVID-19 main protease (6LU7). J. Coord. Chem., 76(5-6), 830-846.
[3] Raman, N., Johnson Raja, S., & Sakthivel, A., (2009). Transition metal complexes with Schiff-base ligands: 4-aminoantipyrine based derivatives–a review. J. Coord. Chem., 62(5), 691-709. ‏
[4] Poormohammadi, E. B., Behzad, M., Abbasi, Z., & Astaneh, S. D. A., (2020). Copper complexes of pyrazolone-based Schiff base ligands: Synthesis, crystal structures and antibacterial properties.  J. Mol. Struct., 1205,127603. ‏
[5] Yadav, P., Kumari, M., Jain, Y., Agarwal, M., & Gupta, R., (2020). Antipyrine based Schiff’s base as a reversible fluorescence turn “off-on-off” chemosensor for sequential recognition of Al3+ and F− ions: A theoretical and experimental perspective. Spectrochim. Acta A Mol. Biomol. Spectrosc., 227, 117596.
[6] Mandal, S., Mondal, M., Biswas, J. K., Cordes, D. B., Slawin, A. M., Butcher, R. J., Saha, M., & Saha, N. C., (2018). Synthesis, characterization and antimicrobial activity of some nickel, cadmium and mercury complexes of 5-methyl pyrazole-3yl-N-(2′-methylthiophenyl) methyleneimine, (MPzOATA) ligand. J. Mol. Struct., 1152, 189-198.
[7] Wang, W. Jin, L., & Yu, Z., (2012). A Highly Active Ruthenium(II) Pyrazolyl–Pyridyl–Pyrazole Complex Catalyst for Transfer Hydrogenation of Ketones. Organometallics., 31(15), 5664-5667.
[8] Haiduc, I., (2019). ReviewInverse coordination. Organic nitrogen heterocycles as coordination centers. A survey of molecular topologies and systematization. Part 1. Five-membered and smaller rings. J. Coord. Chem., 72(13), 2127-2159.
[9] Matada, M. N., & Jathi, K., (2019). Pyrazole-based azo-metal(II) complexes as potential bioactive agents: synthesis, characterization, antimicrobial, anti-tuberculosis, and DNA interaction studies. J. Coord. Chem., 72(12), 1994-2014. ‏
[10] Mandal, S., Das, M., Das, P., Samanta, A., Butcher, R. J., Saha, M., Alswaidan, I. A., L., Rhyman, Ramasami, P., & Saha, N. C., (2019). Synthesis, characterization, DFT and antimicrobial studies of transition metal ion complexes of a new schiff base ligand, 5-methylpyrazole-3yl-N-(2́-hydroxy phenyl amine) methyleneimine, (MPzOAP). J. Mol. Struct., 1178, 100-111.
[11] Marchetti, F., Pettinari, C., Di Nicola, C., Tombesi, A., & Pettinari, R., (2019). Coordination chemistry of pyrazolone-based ligands and applications of their metal complexes.  Coord. Chem. Rev., 401, 213069. ‏
[12] Marchetti, F., Pettinari, C., & Pettinari, R., (2005). Acylpyrazolone ligands: Synthesis, structures, metal coordination chemistry and applications. Coord. Chem. Rev., 249 (24), 2909–2945.
[13] Casas, J. S., Garcia-Tasende, M. S., Sanchez, A., Sordo, J., & Touceda, A., (2007). Coordination modes of 5-pyrazolones: A solid-state overview. Coord. Chem. Rev., 251, 1561-1589.
[14] Marchetti, F., Pettinari, R., & Pettinari, C., (2015). Recent advances in acylpyrazolone metal complexes and their potential applications. Coord. Chem. Rev., 303, 1–31.
[15] Berhanu, A.L., Mohiuddin, I., Malik, A.K., Aulakh, J.S., Kumar, V. & Kim, K.H., (2019). A review of the applications of Schiff bases as optical chemical sensors. TrAc Trend. Anal. Chem., 116, 74-91.
[16] Antony, R., Arun, T., & Manickam S. T. D., (2019). A review on applications of chitosan-based Schiff bases. Int. J. Biol. Macromol.,129, 615-633.
[17] Zhang, J., Xu, L. & Wong, W.Y., (2018). Energy materials based on metal Schiff base complexes. ‏ Coord. Chem. Rev., 355, 180-198.
[18] Liu, X., Manzur, C., Novoa, N., Celedón, S., Carrillo, D. & Hamon, J.R., (2018). Multidentate unsymmetrically-substituted Schiff bases and their metal complexes: Synthesis, functional materials properties, and applications to catalysis.  Coord. Chem. Rev., 357, 144-172.
[19] Kaczmarek, M.T., Zabiszak, M., Nowak, M. & Jastrzab, R., (2018). Lanthanides: Schiff base complexes, applications in cancer diagnosis, therapy, and antibacterial activity. ‏ Coord. Chem. Rev., 370, 42-54.
[20] Iscen, A., Brue, C.R., Roberts, K.F., Kim, J., Schatz, G.C. & Meade, T.J., (2019). Inhibition of Amyloid-β Aggregation by Cobalt(III) Schiff Base Complexes: A Computational and Experimental Approach. J. Am. Chem. Soc. 141, 16685-16695. 
[21] Siegel, R.L., Miller, K.D. & Jemal, A., (2015). Cancer statistics, 2015. Statistics CA: Cancer J. Clin., 65(1), 5-29. ‏
[22] Czarnomysy, R., Surażyński, A., Muszynska, A., Gornowicz, A., Bielawska, A. & Bielawski, K., (2018). A novel series of pyrazole-platinum(II) complexes as potential anti-cancer agents that induce cell cycle arrest and apoptosis in breast cancer cells. J. Enzym. Inhib. Med. Chem., 33, 1006-1023.
[23] Kachalaki, S., Ebrahimi, M., Khosroshahi, L.M., Mohammadinejad, S. & Baradaran, B., (2016).  Cancer chemoresistance; biochemical and molecular aspects: a brief overview. Eur. J. Pharmaceut. Sci., 89, 20-30.
 
[24] Palanimurugan, A., &   Kulandaisamy A., (2018).  DNA, in vitro antimicrobial/anticancer activities and biocidal based statistical analysis of Schiff base metal complexes derived from salicylalidene-4-imino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one and 2-aminothiazole. J. Organomet. Chem., 861, 263-274.
[25] Palanimurugan, A.,  Dhanalakshmi, A.,  Selvapandian, P., & Kulandaisamy A., (2019).   Electrochemical behavior, structural, morphological, Calf Thymus-DNA interaction and in-vitro antimicrobial studies of synthesized Schiff base transition metal complexes. Heliyon, 5(7), e02039. ‏
[26] 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. ‏ Sci. Rep. 9, 5237.
[27] a) Matada, M.N. & Jathi, K., (2019). Pyrazole-based azo-metal(II) complexes as potential bioactive agents: synthesis, characterization, antimicrobial, anti-tuberculosis, and DNA interaction studies. ‏J. Coord. Chem., 72 (12), 1994-2014. b)  Kumar, V., El-Massaoudi, M., Radi, S., Van Hecke, K., Rotaru, A. & Garcia, Y., (2020). Iron(ii) coordination pyrazole complexes with aromatic sulfonate ligands: the role of ether. New J. Chem., 44(32),13902-13912. ‏
[28] Kacar, S.,  Unver, H., & Sahinturk, V., (2020).  A mononuclear copper(II) complex containing benzimidazole and pyridyl ligands: Synthesis, characterization, and antiproliferative activity against human cancer cells.  Arabian. J. Chem., 13(2), 4310-4323. ‏
[29] Sakai, K., Tomita, Y., Ue, T., Goshima, K., Ohminato, M., Tsubomura, T., Matsumoto, K., Ohmura, K., & Kawakami, K., (2000).  Syntheses, antitumor activity, and molecular mechanics studies of cis-PtCl2(pzH)2 (pzH=pyrazole) and related complexes. Crystal structure of a novel Magnus-type double-salt [Pt(pzH)4] [PtCl4][cis-PtCl2(pzH)2]2 involving two perpendicularly aligned 1D chains. Inorg. Chim. Acta., 297, 64-71. ‏
[30] Aljuhani, E., Aljohani, M.M., Alsoliemy, A., Shah, R., Abumelha, H.M., Saad, F.A., Hossan, A., Al-Ahmed, Z.A., Alharbi, A., & El-Metwaly, N.M., (2021). Synthesis and characterization of Cu(II)-pyrazole complexes for possible anticancer agents; conformational studies as well as compatible in-silico and in-vitro assays. Heliyon, 7(11), e08485. ‏
[31] Ali, P., Meshram, J., Sheikh, J., Tiwari, V., Dongre, R., & Hadda, T.B., (2012). Predictions and correlations of structure activity relationship of some aminoantipyrine derivatives on the basis of theoretical and experimental ground. Med. Chem. Res., 21, 157-164.
[32] Layek, S., Ganguly, R., & Pathak, D. D., (2018). Unprecedented formation of a μ-oxobridged polymeric copper(II) complex: Evaluation of catalytic activity in synthesis of 5-substituted 1H-tetrazoles. J. Org. Chem., 870, 16-22.
[33] Selvakumar, P. M., Suresh, E., & Subramanian, P. S., (2007). Synthesis, spectral characterization and structural investigation on some 4-aminoantipyrine containing Schiff base Cu(II) complexes and their molecular association. Polyhedron, 26(4), 749-756.
[34] Medzhidov, A. A., Fatullaeva, P. A., Peng, S. M., Ismaiylov, R. G., Lee, G. H., & Garaeva, S. R., (2012). Oxidative dehydrogenation of N-(2-hydroxy-3,5-R1, R2-benzyl)-4-aminoantipyrines in the complexation reaction. Russ. J. Coord. Chem., 38, 126-133.
[35] Raman, N., Johnson Raja, S., & Sakthivel, A., (2009). Transition metal complexes with Schiff-base ligands: 4-aminoantipyrine based derivatives–a review. J. Coord. Chem,  62(5), 691-709. ‏
[36] Liu, Z.C., Yang, Z.Y., Li, T.R., Wang, B.D., Li, Y., & Wang, M.F., (2011). DNA-binding, antioxidant activity and solid-state fluorescence studies of copper(II), zinc(II) and nickel(II) complexes with a Schiff base derived from 2-oxo-quinoline-3-carbaldehyde. Transition Met Chem., 36, 489-498.
[37] Fatullayeva, P. A., Medjidov, A. A., Maharramov, A. M., Gurbanov, A. V., Askerov, R. K., Rahimov, K. Q., Kopylovich, M. N., Mahmudov, K. T., & Pombeiro A. J., (2012). New cobalt(II) and nickel(II) complexes of 2-hydroxy-benzyl derivatives of 4-aminoantipyrine. Polyhedron, 44(1), 72-76.
[38] Parvarinezhad, S., Salehi, M., Kubicki, M., & Khaleghian A., (2021). Unprecedented formation of a μ-oxobridged dimeric copper (II) complex: Evaluation of structural, spectroscopic, and electronic properties by using theoretical studies and investigations biological activity studies of new Schiff bases derived from pyrazolone. Appl. Organomet. Chem., 35(12), e6443.
‏
[39] Parvarinezhad, S., Salehi, Kubicki, M., & Eshaghi Malekshah, R., (2022). Synthesis, characterization, spectral studies and evaluation of noncovalent interactions in co-crystal of μ-oxobridged polymeric copper(II) complex derived from pyrazolone by theoretical studies. J. Mol.  Struct., 1260,132780.
[40] Parvarinezhad, S., Salehi, M., Eshaghi Malekshah, R., Kubicki, M., & Khaleghian, A., (2022). Synthesis, characterization, spectral studies two new transition metal complexes derived from pyrazolone by theoretical studies, and investigate anti-proliferative activity. Appl. Organomet. Chem., 36(3), e6563.
[41] Huang, L., & Chen, D.B., (2005). link to html4-{[(1E)- (3,5-Dibromo-2 hydroxy­phen­yl) methyl­ene] ­amino}-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one. Act Crystallogr, E., 61(12), o4169-o4170.
[42] Selvakumar, P.M., Suresh, E., & Subramanian, P.S., (2007). Synthesis, spectral characterization and structural investigation on some 4-aminoantipyrine containing Schiff base Cu(II) complexes and their molecular association. Polyhedron., 26(4), 749-756.
[43] Zhang, X., (2011). Syntheses, Crystal Structures and Antibacterial Activities of Two Antipyrine Derivatives. J. Chem. Crystallogr, 41(7), 1044-1048.
[44] Mohamed, S.K., Mague, J.T., Akkurt, M., Albayati, M.R., & Mohamed, A.F., (2017). 4-{(E)-[(2-Hy­dr­oxy­naphthalen-1-yl) methyl­ idene] amino}-1,5-di­methyl-2-phenyl-2,3-di­ hydro-1H-pyrazol-3-one: a new polymorph (β-phase). IUCrData., 2(8), x171166. 
 
[45] Ouennoughi, Y., Eddine Karce, H., Aggoun, D., Lanez, T., Ruiz-Rosas, R., Bouzerafa, B., Ourari, A., Morallon, E., (2017). A novel ferrocenic copper(II) complex Salen-like, derived from 5-chloromethyl-2-hydroxyacetophenone and N ferrocenmethylaniline: Design, spectral approach and solvent effect towards electrochemical behavior of Fc+/Fc redox couple, J. Organ. Chem., 848, 344-351.
[46] Deilami, A.B., Salehi, M., Arab, A. & Amiri, A., (2018). Synthesis, crystal structure, electrochemical properties and DFT calculations of three new Zn(II), Ni(II) and Co(III) complexes based on 5-bromo-2-((allylimino)methyl) phenol Schiff-based ligand. Inorganica Chim. Acta, 476, 93-100. ‏
[47] Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Montgomery Jr, J.A., Vreven, T., Kudin, K.N., Burant, J.C., Millam, J.M., Iyengar, S.S., Tomasi, J., Barone, V., et al., (2009), Gaussian 09 (Linux version).
[48] El-Ayaan, U., El-Metwally, N.M., Youssef, M.M., & El Bialy, S.A., (2007). Perchlorate mixed–ligand copper(II) complexes of β-diketone and ethylene diamine derivatives: Thermal, spectroscopic and biochemical studies. Spectrochim. Acta A., 68, 1278-1286.
[49] Ray, R.K., & Kauffman, G.R., (1990). EPR Spectra and covalency of bis(amidinourea/O-alkyl-1-amidinourea) copper (II) complexes Part II. Properties of the CuN42− chromophore.  Inorg. Chim. Acta., 173, 207-214.
 
[50] Mashat, K.H., Babgi, B.A., Hussien, M.A., Arshad, M.N., & Abdellattif, M.H., (2019). Synthesis, structures, DNA-binding and anticancer activities of some copper(I)-phosphine complexes. Polyhedron, 158, 164-172.
[51] Parvarinezhad, S., Salehi, M., Kubicki, M., & Malekshah, R. E., (2022). Experimental and theoretical studies of new Co(III) complexes of hydrazide derivatives proposed as multi-target inhibitors of SARS-CoV-2. Appl. Organomet. Chem., 36(10), e6836. ‏
[52] Gholivand, K., Barzegari, A., Yousefian, M., Malekshah, R.E., & Faraghi, M., (2023). Experimental and theoretical evaluation of biological properties of a phosphoramide functionalized graphene oxide Biocatal. Agric. Biotechnol, 47, 102612. ‏
[53] Gholivand, K., Sabaghian, M., & Malekshah, R. E., (2021). Synthesis, characterization, cytotoxicity studies, theoretical approach of adsorptive removal and molecular calculations of four new phosphoramide derivatives and related graphene oxide. Bioorg. Chem., 115, 105193.
[54] Ramezanipoor, S., Parvarinezhad, S., Salehi, M., Grześkiewicz, A. M., & Kubicki, M., (2022). Crystal structures, electrochemical properties and theoretical studies of three New Zn(II), Mn(III) and Co(III) Schiff base complexes derived from 2-hydroxy-1-allyliminomethyl-naphthalen. J. Mol.  Struct., 1257, 132541. ‏‏
[55] Sepehrfar, S., Salehi, M., Parvarinezhad, S., Grześkiewicz, A.M., & Kubicki, M., (2023). New Cu(II), Mn(II) and Mn(III) Schiff base complexes cause noncovalent interactions: X-ray crystallography survey, Hirshfeld surface analysis and molecular simulation investigation against SARS-CoV-2. J. Mol.  Struct., 1278, 134857.
[56] Saad, F.A., Elghalban, M.G., El‐Metwaly, N.M., El‐Ghamry, H., & Khedr, A.M., (2017). Density functional theory/B3LYP study of nanometric 4-(2,4-dihydroxy-5-formylphen-1-ylazo)-N-(4-methylpyrimidin-2-yl) benzene sulfonamide complexes: Quantitative structure–activity relationship, docking, spectral and biological investigations. Appl. Organomet. Chem., 31, ec3721.
[57] Ali, P., Meshram, J., Sheikh, J., Tiwari, V., Dongre, R., & Hadda, T.B., (2012). Predictions and correlations of structure activity relationship of some aminoantipyrine derivatives on the basis of theoretical and experimental ground. Med. Chem. Res., 21, 157–164.
[58] Fatullayeva, P.A., Medjidov, A.A., Maharramov, A.M., Gurbanov, A.V., Askerov, R.K., Rahimov, K.Q., Kopylovich, M.N., Mahmudov, K.T., & Pombeiro, A.J., (2012). New cobalt(II) and nickel(II) complexes of 2-hydroxy-benzyl derivatives of 4-aminoantipyrine. Polyhedron., 44(1), 72-76.
[59] Loukopoulos, E., Berkoff, B., Abdul‐Sada, A., Tizzard, G.J., Coles, S.J., Escuer, A., & Kostakis, G.E., (2015). A Disk-Like CoII3DyIII4 Coordination Cluster Exhibiting Single Molecule Magnet Behavior. Eur. J. Inorg. Chem., 2015, 2646– 2649.
[60] El-Sonbati, A.Z., El-Mogazy, M.A., Nozha, S.G., Diab, M.A., Abou-Dobara, M.I., Eldesoky, A.M., & Morgan, S.M., (2022). Mixed ligand transition metal(II) complexes: Characterization, spectral, electrochemical studies, molecular docking and bacteriological application. J. Mol. Struc., 1248, 131498.
[61] El-Sonbati, A.Z., Diab, M.A., Morgan, S.M., Abou-Dobara, M.I., & El-Ghettany, A.A., (2020). Synthesis, characterization, theoretical and molecular docking studies of mixed-ligand complexes of Cu(II), Ni(II), Co(II), Mn(II), Cr(III), UO2(II) and Cd(II). J. Mol. Struct., 1200, 127065.
[62] El-Metwally, N.M., El-Shazly, R.M., Gabr, I.M., & El-Asmy, A.A., (2005). Physical and spectroscopic studies on novel vanadyl complexes of some substituted thiosemicarbazides. Spectrochim. Acta A, 61, 1113-1119.
[63] Lever, A.B.P., (1986). Inorganic Electronic Spectroscopy.  Elsevier, Amsterdam.
[64] Selvakumar, P. M., Suresh, E., & Subramanian, P. S., (2007). Synthesis, spectral characterization and structural investigation on some 4-aminoantipyrine containing Schiff base Cu(II) complexes and their molecular association. Polyhedron, 26(4), 749-756. ‏
[65] Hökelek, T., Kiliç, Z., ISIKLAN, M., & Hayvali, M., (2002). Crystal structure of 4-{[(1E)- (2-hydroxynaphthyl) methylidene] amino}-1, 5-di methyl-2-phenyl-2, 3-dihydro-1H-pyrazol-3-one‏. Anal. Sci., 18, 215-216.
[66] Zhou, Y.H., Liu, X.W., Chen, L.Q., Wang, S.Q., & Cheng, Y., (2016). Synthesis, structure and superoxide dismutase-like activity of two mixed-ligand Cu(II) complexes with N, N′-bis(2-pyridylmethyl) amantadine, Polyhedron., 117, 788-794. ‏
[67] Mandal, S., Chatterjee, S., Modak, R., Sikdar, Y., Naskar, B., & Goswami, S., (2014). Syntheses, crystal structures, spectral studies, and DFT calculations of two new square planar Ni(II) complexes derived from pyridoxal-based Schiff base ligands. J. Coord. Chem., 67(4), 699-713.
[68] Grabowski, S.J., (2011).  What Is the Covalency of Hydrogen Bonding? Chem. Rev., 111(4), 2597-2625.
[69] Ruiz, A., Pérez, H., Morera-Boado, C., Almagro, L., da Silva, C.C., Ellena, J., de la Vega, J.M.G., Martínez-Álvarez, R., Suárez, M., & Martín, N., (2014). Unusual hydrogen bond patterns contributing to supramolecular assembly: conformational study, Hirshfeld surface analysis and density functional calculations of a new steroid derivative. CrystEngComm., 16(33), 7802-7814. ‏
[70] Shi, L., Zheng, H., Hu, W., Zhou, B., Dai, X., Zhang, Y., Liu, Z., Wu, X., Zhao, C., & Liang, G., (2017). Niclosamide inhibition of STAT3 synergizes with erlotinib in human colon cancer. Onco Targets Ther., 10,1767-1776. ‏
Applied Chemistry Today
Volume 18, Issue 69
December 2023
Pages 113-136

Files

Share

How to cite

Statistics