Synthesis, Structural Characterization, Molecular Modeling and DNA Binding Ability of CoII, NiII, CuII, ZnII, PdII and CdII Complexes of Benzocycloheptenone Thiosemicarbazone Ligand

Author(s): Hoda A. El-Ghamry*, Mohamed Gaber, Thoraya A. Farghaly

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 19 , Issue 13 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background & Objective: Six novel complexes of transition metal namely, [CoLCl2(H2O)2]0.5H2O, [NiLCl2(H2O)2]0.5H2O, [CuLCl2]0.5H2O, [ZnLCl2], [PdLCl2]H2O and [CdLCl2]H2O, where L is benzocycloheptenone thiosemicarbazone ligand, have been obtained. The confirmation of the structures of the obtained metal chelates depends on the different spectral and physicochemical techniques including CHN analysis, infrared spectra, molar conductivity measurement, UV-vis, thermogravimetric analysis and magnetic moment. The infrared spectral results ascertained that the ligand behaved as neutral bidentate connecting the metal centers via N and S atoms of C=N and C=S groups, respectively.

Methods: The UV-Vis, molar conductivity and magnetic susceptibility results implied that the geometrical structures of the metal chelates are octahedral for Co(II) & Ni(II) complexes, tetrahedral for Zn(II) & Cd(II) complexes and square planar for Cu(II) & Pd(II) complexes which have been confirmed by molecular modeling studies.

Conclusion: Moreover, the mode of interaction between some chosen metal complexes towards SSDNA has been thoughtful by UV-Vis spectra and viscosity measurements. The value of the intrinsic binding constant (Kb) for the examined compounds has been found to be lower than the binding affinity of the classical intercalator ethedium bromide. Also, the viscosity measurements of the complexes proved that they bind to DNA, most likely, by a non-intercalative mode like H-bonding or electrostatic interactions.

Keywords: Thiosemicarbazone, metal complexes, spectroscopy, DNA binding, molecular modeling.

Afrasiabi, Z.; Sinn, E.; Chen, J.; Ma, Y.; Rheingold, A.L.; Zakharov, L.N.; Rath, N.; Padhye, S. Appended 1,2-naphthoquinones as anticancer agents 1: Synthesis, structural, spectral and antitumor activities of ortho-naphthaquinone thiosemicarbazone and its transition metal complexes. Inorg. Chim. Acta, 2004, 357, 271-278.
Liberta, A.E.; West, D.X. Antifungal and antitumor activity of heterocyclic thiosemicarbazones and their metal complexes: Current status. Biometals, 1992, 5, 121-126.
Nandi, A.K.; Chaudhri, S.; Mazumdah, S.K.; Ghosh, S. Effect of chlorine substitution on the structure and activity of 4- phenylthiosemicarbazide: crystal and molecular structure of 4-(4-chlorophenyl) thiosemicarbazide. J. Chem. Soc. Perkin Trans., 1984, 2, 1729-1733.
Ali, M.A.; Chowdhary, D.A.; Naziruddin, M. Four- and five-coordinate copper(II) complexes containing mixed ligands. Polyhedron, 1984, 5, 595-598.
Scovill, J.P.; Klayman, D.L.; Franchino, C.F. 2-Acetylpyridine thiosemicarbazones. 4 Complexes with transition metals as antimalarial and antileukemic agents. J. Med. Chem., 1982, 10, 1261-1264.
Hossain, M.E.; Alam, M.N. Begum, Akbar, A.J.M; Nazimuddin, M; Smith, F.E; Hynes, R.C. The preparation, characterization, crystal structure and biological activities of some copper(II) complexes of the 2-benzoylpyridine Schiff bases of S-methyl- and Sbenzyldithiocarbazate. Inorg. Chim. Acta A, 1996, 249, 207-213.
Bindu, P.; Kurup, M.R.P.; Satyakeerty, T.R. Cyclic voltammetric and biological activities of copper(II) complexes of salicylaldehyde N (4)-substituted thiosemicarbazone and heterocyclic bases. Polyhedron, 1999, 18, 321-331.
Borges, R.H.U.; Paniago, E.; Beraldo, H. Equilibrium and kinetic studies of iron(II) and iron(III) complexes of some α(N)-heterocyclic thiosemicarbazones. Reduction of the iron(III) complexes of 2- formylpyridine thiosemicarbazone and 2- acetylpyridine thiosemicarbazone by cellular thiol-like reducing agents. J. Inorg. Biochem., 1997, 65, 267-275.
Baldini, M.; Belicchi-Ferrari, M.; Bisceglle, F.; Agllo, P.P.D.; Pelos, G.; Pinelli, S.; Tarasconi, P. Copper(II) complexes with substituted thiosemicarbazones of α-ketoglutaric acid: Synthesis, X-ray structures, DNA binding studies, and nuclease and biological activity. J. Inorg. Chem, 2004, 43, 7170-7179.
Yadagiri, B.; Holagunda, U.D.; Bantu, R.; Nagarapu, L.; Guguloth, V.; Polepally, S.; Jain, N. Rational design, synthesis and anti-proliferative evaluation of novel benzosuberone tethered with hydrazidehydrazones. Bioorg. Med. Chem. Lett., 2014, 24, 5041-5544.
Nagarapu, L.; Yadagiri, B.; Bantu, R.; Kumar, C.G.; Pombala, S.; Nanubolu, J. Studies on the synthetic and structural aspects of benzosuberones bearing 2, 4-thiazolidenone moiety as potential anti-cancer agents. Eur. J. Med. Chem., 2014, 71, 91-97.
Yadagiri, B.; Holagunda, U.D.; Bantu, R.; Nagarapu, L.; Kumar, C.G.; Pombala, S.; Sridhar, B. Synthesis of novel building blocks of benzosuberone bearing coumarin moieties and their evaluation as potential anticancer agents. Eur. J. Med. Chem., 2014, 79, 260-265.
Gad, W.A.; Nassar, D.O. The utility of 8-fluoro-1-benzosuberone in synthesis of newly; Azole, pyrane and pyrimidine derivatives as cytotoxic and anti-tumor agents. Org. Chem.: Indian J., 2014, 10(10), 398-405.
Tajik, S.; Tahera, M.A.; Beitollahi, H. Mangiferin DNA biosensor using double-stranded DNA modified pencil graphite electrode based on guanine and adenine signals. J. Electroanal. Chem., 2014, 720, 134-138.
Tajika, S.; Tahera, M.A.; Beitollahi, H.; Mahani, M.T. Electrochemical determination of the anticancer drug taxol at a ds-DNA modified pencil-graphite electrode and its application as a label-free electrochemical biosensor. Talanta, 2015, 134, 60-64.
Alaghaz, A.M.A.; El-Sayed, B.A.; El-Henawy, A.A.; Ammar, R.A.A. Synthesis, spectroscopic characterization, potentiometric studies, cytotoxic studies and molecular docking studies of DNA binding of transition metal complexes with 1,1-diaminopropane–Schiff base. J. Mol. Struct.,2013, 1035, 83-93; (b) Karastogianni, S.; Dendrinou-Samara, C.; Ioannou, E.; Raptopoulou, C.P.; Hadjipavlou-Litina, D.; Girousi, S.J. Synthesis, characterization, DNA binding properties and antioxidant activity of a manganese(II) complex with NO6 chromophore. Inorg. Biochem.,2013, 118, 48-58; (c) Pathan, A.H.; Bakale, R.P.; Naik, G.N.; Frampton, C.S.; Gudasi, K.B. Synthesis, crystal structure, redox behavior and comprehensive studies on DNA binding and cleavage properties of transition metal complexes of a fluoro substituted thiosemicarbazone derived from ethyl pyruvate. Polyhedron,2012,34, 149-156; (d) Kulkarni, N.V.; Kamath, A.; Budagumpi, S.; Revankar, V.K. Pyrazole bridged binuclear transition metal complexes: Synthesis, characterization, antimicrobial activity and DNA binding/cleavage studies. J. Mol. Struct., 2011, 1006, 580-588.
Tian, J.L.; Liu, X.; Yan, S.P.; Kelland, L. The resurgence of platinum-based cancer chemotherapy. Nat. Rev. Cancer, 2007, 7, 573-584.
Busto, N.; Valladolid, J.; Alonso, M.M.; Lozano, H.J.; Jalón, F.A.; Manzano, B.R.; Rodríguez, A.M.; Carrión, M.C.; Biver, T.; Leal, J.; Espino, G.; García, B. Anticancer activity and DNA binding of a bifunctional Ru(II) arene aqua-complex with the 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine ligand. Inorg. Chem., 2013, 52, 9962-9974.
Zuber, G.; Quada, J.C.; Hecht, S.M. Mechanistic organic chemistry in a microreactor. Zeolite-controlled photooxidations of organic sulfides. J. Am. Chem. Soc., 1998, 120, 9368-9378.
(a)Li, G.Y.; Du, K.J.; Wang, J.Q.; Liang, J.W.; Kou, J.F.; Hou, X.J.; Ji, L.N.; Chao, H. Synthesis, crystal structure, DNA interaction and anticancer activity of tridentate copper(II) complexes. J. Inorg. Biochem., 2013, 119, 43-53.
(b)Patel, M.N.; Joshi, H.N.; Patel, C.R. Cytotoxic, antibacterial, DNA interaction and superoxide dismutase like activities of sparfloxacin drug based copper(II) complexes with nitrogen donor ligands. Spectrochim. Acta A, 2013, 104, 48-55.
(c)Xue, F.; Xie, C.Z.; Zhang, Y.W.; Qiao, Z.; Qiao, X.; Xu, J.Y.; Yan, S-P. Two new dicopper(II) complexes with oxamido-bridged ligand: Synthesis, crystal structures, DNA binding/cleavage and BSA binding activity. J. Inorg. Biochem., 2012, 115, 78-86.
(d)Reddy, P.R.; Shilpa, A.; Raju, N.; Raghavaiah, P. Synthesis, structure, DNA binding and cleavage properties of ternary amino acid schiff base-phen/bipy Cu(II) complexes. J. Inorg. Biochem., 2011, 105, 1603-1612.
(a)Farghaly, T.A.; Abbas, E.M.H. Hydrazonoyl halides as precursors for synthesis of novel bioactive thiazole and formazan derivatives. J. Chem. Res., 2012, 660-664.
(b)Dimmock, J.R.; Pandeya, S.N.; Quail, J.W.; Pugazhenthi, U.; Allen, T.M.; Kao, G.Y.; Balzarini, J.; DeClercq, E. Evaluation of the semicarbazones, thiosemicarbazones and bis-carbohydrazones of some aryl alicycylic ketones for anticonvulsant and other biological propertie. Eur. J. Med. Chem., 1995, 30(4), 303-314.
Hyper Chem. Version 8.03 Hypercube, Inc.
Marmur, J. A procedure for the isolation of deoxyribonucleic acid from micro-organisms. J. Mol. Biol., 1961, 3, 208-218.
Geary, W.J. The use of conductivity measurements in organic solvents for the characterisation of coordination compounds. Coord. Chem. Rev., 1971, 7, 81-122.
Netalkar, P.P.; Netalkar, S.P.; Revankar, V.K. Transition metal complexes of thiosemicarbazone: Synthesis, structures and in vitro antimicrobial studies. Polyhedron, 2015, 100, 215-222.
El-Ghamry, H.; Sakai, K.; Masaoka, S.; El-Baradie, K.; Issa, R. Synthesis and characterization of self-assembled coordination polymers of N-diaminomethylene-4-(3-formyl-4-hydroxy-phenylazo)-benzenesulfonamide. J. Coord. Chem., 2012, 65(2), 780-794.
Yousef, T.A.; Abu El-Reash, G.M.; El-Gammal, O.A.; Ahmed, S.F. Structural, DFT and biological studies on Cu(II) complexes of semi and thiosemicarbazide ligands derived from diketo hydrazide. Polyhedron, 2014, 81, 749-763.
El-Gammal, O.A.; Abu El-Reash, G.M.; Ghazy, S.E.; Yousef, T.A. Heterocyclic substituted thiosemicarbazides and their Cu(II) complexes: Synthesis, spectral characterization, thermal, molecular modeling, and DNA degradation studies. J. Coord. Chem., 2012, 65(10), 1655-1671.
Despaigne, A.A.R.; Da Silva, J.G.; Do Carmo, A.C.M.; Piro, O.E.; Castellano, E.E.; Beraldo, H. Copper(II) and zinc(II) complexes with 2-benzoylpyridine-methyl hydrazine. J. Mol. Struct., 2009, 920, 97-102.
Joseyphus, R.S.; Dhanaraj, C.J.; Nair, M.S. Synthesis and characterization of some schiff base transition metal complexes derived from vanillin and L (+)alanine. Transition Met. Chem., 2006, 31, 699-702.
Seena, E.B.; Kurup, M.R.P. Spectral and structural studies of mono- and binuclear copper(II) complexes of salicylaldehyde N (4)-substituted thiosemicarbazones. Polyhedron, 2000, 26, 829-836.
El-Sonbati, A.Z.; Diab, M.A.; El-Bindary, A.A.; Nozha, S.G. Structural and characterization of novel copper(II) azodye complexes. Spectrochim. Acta A, 2011, 83, 490-498.
Lever, A.B.P. Inorganic Electronic Spectroscopy, 2nd ed; Elsevier: Amsterdam, 1984.
El-Baradie, K.; El-Sharkawy, R.; El-Ghamry, H.; Sakai, K. Synthesis and characterization of Cu(II), Co(II) and Ni(II) complexes of a number of sulfadrug azodyes and their application for wastewater treatment. Spectrochim. Acta A, 2014, 121, 180-187.
Vinuelas-Zahınos, E.; Maldonado-Rogado, M.A.; Luna, G.F.; Barros, G.F.J. Coordination behaviour of Schiff base 2-acetyl-2-thiazoline hydrazone (ATH) towards cobalt(II), nickel(II) and copper(II). Polyhedron, 2008, 27, 879-886.
Bessy, R.B.N.; Prathapachandra, K.M.R.; Suresh, E. Synthesis, spectral characterization and crystal structure of N-2-hydroxy-4-methoxybenzaldehyde-N′-4-nitrobenzoyl hydrazone and its square planar Cu(II) complex. Spectrochim. Acta A, 2008, 71, 1253.
Tarafder, M.T.; Kasbollah, A.; Crouse, K.A.; Ali, A.M.; Yamin, B.M.; Fun, H.K. Synthesis and characterization of Zn(II) and Cd(II) complexes of S-benzyl-β-N-(2-pyridyl) methylene dithiocarbazate (HNNS): Bioactivity of the HNNS Schiff base and its Zn(II), Cu(II) and Cd(II) complexes and the X-ray structure of the [Zn(NNS)2]. Polyhedron, 2001, 20, 2363-2370.
Amer, S.; El-Wakiel, N.; El-Ghamry, H. Synthesis, spectral, antitumor and antimicrobial studies on Cu(II) complexes of purine and triazole Schiff base derivatives. J. Mol. Struc., 2013, 1049-326- 335.
Kumar, D.N.; Garg, B.S. Synthesis and spectroscopic studies of complexes of zinc(II) with N2O2 donor groups. Spectrochim. Acta A, 2006, 64, 141-147.
Gaber, M.; El-Ghamry, H.A.; Fathalla, S.K. Ni(II), Pd(II) and Pt(II) complexes of (1H-1,2,4-triazole-3-ylimino) methyl] naphthalene-2-ol. Structural, spectroscopic, biological, cytotoxicity, antioxidant and DNA binding. Spectrochim Acta Part A, 2015, 139, 396-404.
Yousef, T.A.; Abu El-Reash, G.M.; El Morshedy, R.M. Structural, spectral analysis and DNA studies of heterocyclic thiosemicarbazone ligand and its Cr(III), Fe(III), Co(II) Hg(II), and U(VI) complexes. J. Mol. Struct., 2013, 1045, 145.
Yousef, T.A.; Abu El-Reash, G.M.; El-Morshedy, R.M. Quantum chemical calculations, experimental investigations and DNA studies on (E)-2-((3-hydroxynaphthalen-2-yl) methylene)-N-(pyridin-2-yl) hydrazinecarbothioamide and its Mn(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes. Polyhedron, 2012, 45, 71-85.
El-Baradie, K.Y.; El-Wakiel, N.A.; El-Ghamry, H.A. Synthesis, characterization and corrosion inhibition in acid medium of l‐histidine Schiff base complexes. Appl. Organomet. Chem., 2015, 29(3), 117-112.
Allen, F.H.; Kennard, O.; Watson, D.G.; Brammer, L.; Open, A.G.; Taylor, R.J. Tables of bond lengths determined by X-ray and neutron diffraction. Part 1. Bond lengths in organic compounds. Chem. Soc. Perkin Trans., 1987, 2, S1-S19.
(a)Geerlings, P.; Proft, F.D.; Langenaeker, W. Conceptual density functional theory. Chem. Rev., 2003, 103, 1793-1874.
(b)Parr, R.; Von Szentpaly, L.; Liu, S. Electrophilicity Index. J. Am. Chem. Soc., 1999, 121, 1922-1924.
(c)Chattaraj, P.; Giri, S. Stability, reactivity, and aromaticity of compounds of a multivalent superatom. J. Phys. Chem., 2007, 111, 11116-11121.
(d)Sagdinc, S.; Köksoy, B.; Kandemirli, F.; Bayari, S. Theoretical and spectroscopic studies of 5-fluoro-isatin-3-(N-benzylthiosemicarbazone) and its zinc(II) complex. J. Mol. Struct., 2009, 917, 63-70.
Fukui, K. Role of frontier orbitals in chemical reactions. Science, 1982, 218, 747-754.
Gao, G.; Liang, C. Temperature effects on the corrosion inhibition of carbon steel in acidic solutions by alizarin red. Electrochim. Acta, 2007, 52, 4554-4559.
Mohanraj, M.; Ayyannan, G.; Raja, G.; Jayabalakrishnan, C. Evaluation of DNA binding, DNA cleavage, protein binding, radical scavenging and in vitro cytotoxic activities of ruthenium(II) complexes containing 2,4-dihydroxy benzylidene ligands. Mater. Sci. Eng. C, 2016, 69, 1297-1306.
Pyle, A.M.; Rehmann, J.P.; Meshoyrer, J.P.; Kumar, C.V.; Turro, N.J.; Barton, J.K. Mixed-ligand complexes of ruthenium(II): Factors governing binding to DNA. J. Am. Chem. Soc., 1989, 111, 3051-3058.
Hirohama, T.; Kuranuki, Y.; Ebina, E.; Sugizaki, T.; Arii, H.; Chikira, M.; Selvi, P.T.; Palaniandavar, M. Copper(II) complexes of 1,10-phenanthroline-derived ligands: Studies on DNA binding properties and nuclease activity. J. Inorg. Biochem., 2005, 99, 1205-1219.
El-Sonbati, A.Z.; Diab, M.A.; El-Bindary, A.A.; Ghoneim, M.M.; Mohesien, M.T.; Abd El-Kader, M.K. Polymeric complexes — LXI. Supramolecular structure, thermal properties, SS-DNA binding activity and antimicrobial activities of polymeric complexes of rhodanine hydrazone compounds. J. Mol. Liq., 2016, 215, 711-739.
Li, T.R.; Yang, Z.Y.; Wang, B.D.; Qin, D.D. Synthesis, characterization, antioxidant activity and DNA-binding studies of two rare earth(III) complexes with naringenin-2-hydroxy benzoyl hydrazone ligand. Eur. J. Med. Chem., 2008, 43, 1688-1695.
Wang, B.; Yang, Z.Y.; Crewdson, P.; Wang, D. Synthesis, crystal structure and DNA-binding studies of the Ln(III) complex with 6-hydroxychromone-3-carbaldehyde benzoyl hydrazine. J. Inorg. Biochem., 2007, 101, 1492-1504.
Sarkar, S.; Mondal, A.; Chopra, D.; Ribas, J.; Rajak, K. A Ferromagnetically Coupled, Bent, Trinuclear Copper(II) Complex: Synthesis, Structure, Hydrogen‐Bonding Network, Magnetic Properties and DNA Interaction Study. Eur. J. Inorg. Chem., 2006, 3510-3516.
Chen, J.; Wang, X.; Shao, Y.; Zhu, J.; Zhu, Y.; Li, Y.; Xu, Q.; Guo, Z. A Trinuclear Copper(II) complex of 2,4,6-Tris(di-2-pyridylamine)-1,3,5-triazine shows prominent DNA cleavage activity. Inorg. Chem., 2007, 4, 3306-3312.
Dimitrakopoulou, A.; Dendrinou-Samara, C.; Pantazaki, A.A.; Alexiou, M.; Nordlander, E.; Kessissoglou, D.P. Synthesis, structure and interactions with DNA of novel tetranuclear, [Mn4(II/II/II/IV)] mixed valence complexes. J. Inorg. Biochem., 2008, 102, 618-628.
Wilson, W.D.; Ratmeyer, L.; Zhao, M.; Strekowski, L.; Boykin, D. The search for structure-specific nucleic acid-interactive drugs: Effects of compound structure on RNA versus DNA interaction strength. Biochemistry, 1993, 32, 4098-4104.
Li, F.H.; Zhao, G.H.; Wu, H.X.; Lin, H.; Wu, X.X.; Zhu, S.R.; Lin, H.K. Synthesis, characterization and biological activity of lanthanum(III) complexes containing 2-methylene–1,10-phenanthroline units bridged by aliphatic diamines. J. Inorg. Biochem., 2006, 100, 36-43.
Srishailam, A.; Gabra, N.M.; Kumar, Y.P.; Reddy, K.L.; Devi, C.S.; Anil Kumar, D.; Singh, S.S.; Satyanarayana, S. Synthesis, characterization; DNA binding and antitumor activity of ruthenium(II) polypyridyl complexes. J. Photochem. Photobiol. B, 2014, 141, 47-58.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 20 August, 2019
Page: [1068 - 1079]
Pages: 12
DOI: 10.2174/1389557519666190301143322
Price: $65

Article Metrics

PDF: 19