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Synthesis and Investigation of Bivalent Thiosemicarbazone Complexes: Conformational Analysis, Methyl Green DNA Binding and In-silico Studies

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Abstract

2-(3,4-dihydronaphthalen-1(2H)-ylidene)-N-ethylhydrazine-1-carbothioamide as a thiosemicarbazone derivative (HDEC) was prepared for coordination with Cd(II), Co(II) and Ni(II) ions. The obtained complexes were analyzed and their suggested formulae were [Cd(HDEC)2Cl2], [Co(HDEC)2Cl2] and [Ni(HDEC)2Cl2]. The neutral bidentate mode of bonding via C=S and C=N groups was suggested spectrally. Regarding the Co(II) and Ni(II) complexes, the two characteristic ligand field transitions in Nujol mull as well as the magnetic moment values point to their octahedral shape. The quantum calculations obtained through DFT/B3LYP method as the atomic charges, bond lengths and bond angles confirm the priority of C(8)=S(5) and C(1)=N(6) groups in coordination. Additionally, the maps of frontiers as well as the array plot with iso-surface indicate the reduced polarity of the ligand and its Cd(II) complex. A distinguished antibacterial activity of HDEC was clearly appeared with all bacterial strains which steadily exceeds than the standard drug (Ampicillin). The IC50 values for the colorimetric assay of methyl green DNA binding detect the excellent genotoxicity of the ligand. In-silico assay via Swiss link introduced an impression on the absorption, distribution, metabolism and excretion (ADME) of all compounds. The ligand showed excellent properties that it make it in the rank of promising genotoxic agent which mainly interacted with protease enzyme. Moreover, the molecular docking versus DNA-polymerase indicates the superiority of the ligand in allosteric binding with DNA-pockets. Finally, the interaction of the ligand versus DNA-polymerase cannot being ignored either from the in-vitro or in-silico assessments. Also, the lack of complexes activity may refer to their saturation from ligand coordination which yielded octahedral forms that unable for extra-interaction with the donors of biological systems in living cells.

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References

  1. Casas, J.S.; García-Tasende, M.S.; Sordo, J.: Main group metal complexes of semicarbazones and thiosemicarbazones. Struct. Rev. Coord. Chem. Rev. 209(1), 197–261 (2000)

    Article  Google Scholar 

  2. West, D.X.; Padhye, S.B.; Sonawane, P.B.: Structural and physical correlations in the biological properties of transition metal heterocyclic thiosemicarbazone and S-alkyldithiocarbazate complexes. Struct. Bond. 76, 1–50 (1990)

    Google Scholar 

  3. West, D.X.; Liberta, A.E.; Padhye, S.B.: Thiosemicarbazone complexes of copper (II): structural and biological studies. Coord. Chem. Rev. 123(1–2), 49–71 (1993)

    Article  Google Scholar 

  4. Liberta, A.E.; West, D.X.: Antifungal and antitumor activity of heterocyclic thiosemicarbazones and their metal complexes: current status. Biometals 5(2), 121–126 (1992)

    Article  Google Scholar 

  5. Abu-Dief, A.M.; El-Metwaly, N.M.; Omar Alzahrani, S.; Alkhatib, F.; Abumelha, H.M.; El-Dabea, T.; Abd El Aleem Ali Ali, M.: Structural, conformational and therapeutic studies on new thiazole complexes: drug-likeness and MOE-simulation assessments. Res. Chem. Intermed. 47(5), 1979–2002 (2021)

    Article  Google Scholar 

  6. Abu-Dief, A.M.; El-Metwaly, N.M.; Alzahrani, S.O.; Bawazeer, A.M.; Shaaban, S.; Adam, M.S.S.: Targeting ctDNA binding and elaborated in-vitro assessments concerning novel Schiff base complexes: Synthesis, characterization, DFT and detailed in-silico confirmation. J. Mol. Liq. 322, 114977 (2021)

    Article  Google Scholar 

  7. Sumrra, S.H.; Habiba, U.; Zafar, W.; Imran, M.; Chohan, Z.H.: A review on the efficacy and medicinal applications of metal-based triazole derivatives. J. Coord. Chem. 73(20–22), 2838–2877 (2020)

    Article  Google Scholar 

  8. Alkhamis, K.; Alsoliemy, A.; Aljohani, M.M.; Alrefaei, A.F.; Abumelha, H.M.; Mahmoud, M.H.; Zaky, R.; El-Metwaly, N.M.: Conductometry of nano-sized zinc sulfate; synthesis and characterization of new hydrazone complexes: conformational and in-vitro assay. J. Mol. Liq. 340, 117167 (2021)

    Article  Google Scholar 

  9. Morgan, S.M.; El-Sonbati, A.Z.; Eissa, H.R.: Geometrical structures, thermal properties and spectroscopic studies of Schiff base complexes: Correlation between ionic radius of metal complexes and DNA binding. J. Mol. Liq. 240, 752–776 (2017)

    Article  Google Scholar 

  10. Leovac, V.M.; Novaković, S.B.; Bogdanović, G.A.; Joksović, M.D.; Szécsényi, K.M.; Češljević, V.I.: Transition metal complexes with thiosemicarbazide-based ligands. Part LVI: Nickel(II) complex with 1,3-diphenylpyrazole-4-carboxaldehyde thiosemicarbazone and unusually deformed coordination geometry. Polyhedron 26(14), 3783–3792 (2007)

    Article  Google Scholar 

  11. Netalkar, P.P.; Netalkar, S.P.; Revankar, V.K.: Transition metal complexes of thiosemicarbazone: Synthesis, structures and invitro antimicrobial studies. Polyhedron 100, 215–222 (2015)

    Article  Google Scholar 

  12. Khandar, A.A.; Azar, Z.M.; Eskandani, M.; Hubschle, C.B.; Smaalen, S.; Shaabani, B.; Omidi, Y.: Cadmium(II) complexes of a hydrazone ligand: Synthesis, characterization, DNA binding, cyto- and genotoxicity studies. Polyhedron 171, 237–248 (2019)

    Article  Google Scholar 

  13. Pelosi, G.; Bisceglie, F.; Bignami, F.; Ronzi, P.; Schiavone, P.; Maria, C.R.; Claudio, C.; Elisabetta, P.: Antiretroviral activity of thiosemicarbazone metal complexes. J. Med. Chem. 53(24), 8765 (2010)

    Article  Google Scholar 

  14. Miminoshvili, E.B.: Metal hydrazide complexes. J. Struct. Chem. 50(1), 168–175 (2009)

    Article  Google Scholar 

  15. Antony, R.; David, S.T.; Saravanan, K.; Karuppasamy, K.; Balakumar, S.: Synthesis, spectrochemical characterisation and catalytic activity of transition metal complexes derived from Schiff base modified chitosan. Spectrochim. Acta A 103, 423–430 (2013)

    Article  Google Scholar 

  16. Pelosi, G.: Thiosemicarbazone metal complexes: from structure to activity. Open Crystallogr J 3, 16–28 (2010)

    Article  Google Scholar 

  17. Alzahrani, S.; Morad, M.; Bayazeed, A.; Aljohani, M.M.; Alkhatib, F.; Shah, R.; Katouah, H.; Abumelha, H.M.; Althagafi, I.; Zaky, R.; El-Metwaly, N.M.: Ball milling approach to prepare new Cd (II) and Zn (II) complexes; characterization, crystal packing, cyclic voltammetry and MOE-docking agrees with biological assay. J. Mol. Struct. 1218, 128473 (2020)

    Article  Google Scholar 

  18. Katouah, H.; Sayqal, A.; Al-Solimy, A.M.; Abumelha, H.M.; Shah, R.; Alkhatib, F.; Alzahrani, S.; Zaky, R.; El-Metwaly, N.M.: Facile synthesis and deliberate characterization for new hydrazide complexes; cyclic voltammetry, crystal packing, eukaryotic DNA degradation and in-silico studies. J. Mol. Liq. 320, 114380 (2020)

    Article  Google Scholar 

  19. Frisch, M., Trucks, G., Schlegel, H., Scuseria, G., Robb, M., Cheeseman, J., Scalmani, G., Barone, V., Mennucci, B., Petersson, G., Gaussian. Inc., Wallingford, CT, USA, (2009)

  20. Lee, C.; Yang, W.; Parr, R.G.: Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys. Rev. B 37(2), 785–789 (1988)

    Article  Google Scholar 

  21. Becke, A.D.: Density-functional thermochemistry. III. The role of exact exchange. J. Chem. Phys. 98(7), 5648–5656 (1993)

    Article  Google Scholar 

  22. Dennington, R., Keith, T., Millam, J., GaussView, Ver. 4.1. Semichem Inc., Shawnee Mission, KS (2009)

  23. Al-Hazmi, G.A.A.; Abou-Melha, K.S.; El-Metwaly, N.M.; Althagafi, I.; Shaaban, F.; Zaky, R.: Green synthesis approach for Fe (III), Cu (II), Zn (II) and Ni (II)-Schiff base complexes, spectral, conformational, MOE-docking and biological studies. Appl. Organomet. Chem. 34(3), e5403 (2020)

    Article  Google Scholar 

  24. Burres, N.; Frigo, A.; Rasmussen, R.; McAlpine, J.: A Colorimetric microassay for the detection of agents that interact with DNA. J. Nat. Prod. 55, 1582–1587 (1992)

    Article  Google Scholar 

  25. Daina, A.; Michielin, O.; Zoete, V.: SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 7, 42717 (2017)

    Article  Google Scholar 

  26. Alaysuy, O.; Abumelha, H.M.; Alsoliemy, A.; Alharbi, A.; Alatawi, N.M.; Osman, H.E.M.; Zaky, R.; El-Metwaly, N.M.: Elucidating of new hydrazide-based complexes derived from Pd (II), Cu (II) and Cd (II) ions: studies concerning spectral, DFT, Hirshfeld-crystal, biological screening beside Swiss-ADME verification. J. Mol. Struct. 1259, 132748 (2022)

    Article  Google Scholar 

  27. Al-nami, S.Y.; Aljuhani, E.; Althagafi, I.; Abumelha, H.M.; Bawazeer, T.M.; Al-Solimy, A.M.; Al-Ahmed, Z.A.; Al-Zahrani, F.; El-Metwaly, N.: Synthesis and Characterization for new nanometer Cu (II) complexes, conformational study and molecular docking approach compatible with promising in vitro screening. Arab. J. Sci. Eng. 46, 365–382 (2021)

    Article  Google Scholar 

  28. Almalki, S.A.; Bawazeer, T.M.; Asghar, B.; Alharbi, A.; Aljohani, M.M.; Khalifa, M.E.; El-Metwaly, N.: Synthesis and characterization of new thiazole-based Co (II) and Cu (II) complexes; therapeutic function of thiazole towards COVID-19 in comparing to current antivirals in treatment protocol. J. Mol. Struct. 1244, 130961 (2021)

    Article  Google Scholar 

  29. Jeffery, G.; Bassett, J.; Mendham, J.; Denney, R.: Vogel’s Quantitative Chemical Analysis, 5th edn. Longman Scientific & Technical Longman Group UK Limited, Essex CM20 2JE, England (1989)

    Google Scholar 

  30. Geary, W.J.: The use of conductivity measurements in organic solvents for the characterization of coordination compounds. Coord. Chem. Rev. 7(1), 81–122 (1971)

    Article  Google Scholar 

  31. El-Asmy, A.; Jeragh, B.; Ali, M.: Spectral, thermal, molecularmodeling and biological studies on monoandbinuclear complexes derived from oxalobis(2,3-butanedionehydrazone). Chem. Cent. J. 9, 1–12 (2015)

    Article  Google Scholar 

  32. Nakamoto, K.: Infrared Spectra of Inorganic and Coordination Compounds, p. 1–338. Wiley, New York (1970)

    Google Scholar 

  33. Al-Qahtani, S.D.; Alsoliemy, A.; Almehmadi, S.J.; Alkhamis, K.; Alrefaei, A.F.; Zaky, R.; El-Metwaly, N.M.: Green synthesis for new Co (II), Ni (II), Cu (II) and Cd (II) hydrazone-based complexes; characterization, biological activity and electrical conductance of nano-sized copper sulphate. J. Mol. Struct. 1244, 131238 (2021)

    Article  Google Scholar 

  34. Lever, A.B.P.: Inorganic Electronic Spectroscopy, p. 1–863. Elsevier, Amsterdam (1968)

    Google Scholar 

  35. Cotton, F.A.; Wilkinson, G.; Murillo, C.A.; Bochmann, M.: Advanced inorganic chemistry, 6th edn., p. 1–171. Wiley, New Jersey (2003)

    Google Scholar 

  36. Mehri, M.; Chafai, N.; Ouksel, L.; Benbouguerra, K.; Hellal, A.; Chafaa, S.: Synthesis, electrochemical and classical evaluation of the antioxidant activity of three α-aminophosphonic acids: experimental and theoretical investigation. J. Mol. Struct. 1171, 179–189 (2018)

    Article  Google Scholar 

  37. Al-Hazmi, G.A.A.; Abou-Melha, K.S.; El-Metwaly, N.M.; Althagafi, I.; Shaaban, F.; Zaki, R.: Green synthesis approach for Fe (III), Cu (II), Zn (II) and Ni (II)-Schiff base complexes, spectral, conformational, MOE-docking and biological studies. Appl. Organomet. Chem. 34, e5403 (2020)

    Article  Google Scholar 

  38. Anderson, J.S.M.; Melin, J.; Ayers, P.W.: Conceptual density-functional theory for general chemical reactions, including those that are neither charge- nor frontier-orbital-controlled. 2. Application to molecules where frontier molecular orbital theory fails. Comput. Theor. Chem. 3(2), 375–389 (2007)

    Article  Google Scholar 

  39. Abumelha, H.M.; Al-Fahemi, J.H.; Althagafi, I.; Bayazeed, A.A.; Al-Ahmed, Z.A.; Khedr, A.M.; El-Metwaly, N.M.: deliberate-characterization for Ni (II)-Schiff Base complexes: promising in-vitro anticancer feature that matched MOE docking-approach. J. Inorg. Organomet. Poly. Mater. 30(9), 3277–3293 (2020)

    Article  Google Scholar 

  40. Raman, N.; Muthuraj, V.; Ravichandran, S.; Kulandaisamy, A.: Synthesis, characterization and electrochemical behaviour of Cu(II), Co(II), Ni(II) and Zn(II) complexes derived from acetylacetone and p-anisidine and their antimicrobial activity. Proc. Indian Acad. Sci. 115, 161–167 (2003)

    Article  Google Scholar 

  41. Yousef, T.A.; El-Reash, G.M.A.; 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 81, 749–763 (2014)

    Article  Google Scholar 

  42. Shah, R.K.; Abou-Melha, K.S.; Saad, F.A.; Yousef, T.; Al-Hazmi, G.A.; Elghalban, M.G.; Khedr, A.M.; El-Metwaly, N.M.: Elaborated studies on nano-sized homo-binuclear Mn (II), Fe (III), Co (II), Ni (II), and Cu (II) complexes derived from N2O2 Schiff base, thermal, molecular modeling, drug-likeness, and spectral. J. Therm. Anal. Calorim. 123(1), 731–743 (2016)

    Article  Google Scholar 

  43. Nagar, R.: Syntheses, characterization, and microbial activity of some transition metal complexes involving potentially active O and N donor heterocyclic ligands. J Inorg Biochem 40, 349–356 (1990)

    Article  Google Scholar 

  44. Ramesh, R.; Maheswaran, S.J.: Synthesis, spectra, dioxygen affinity and antifungal activity of Ru(III) Schiff base complexes. J. Inorg. Biochem. 96, 457–462 (2003)

    Article  Google Scholar 

  45. Abdel-Rahman, L.H.; Noamaan, M.A.; Ahmed, H.E.; Adam, M.S.S.: Synthesis, characterization and in vitro pharmacological evaluation of 6,6’-((1E,1’E)-((4-chloro-1,2-phenylene) bis (azaneyl ylidene)) bis(methaneylylidene)) bis (2-ethoxy phenol and its Zr(IV), V(IV), Zn(II) chelates as promising antiproliferative, antimicrobial, antioxidant drug candidates. Bioorg. Chem. 114, 105106 (2021)

    Article  Google Scholar 

  46. Martín-Cordero, C.; López-Lázaro, M.; Gálvez, M.; Jesús Ayuso, M.: Curcumin as a DNA topoisomerase II Poison. J. Enzym. Inhib. Med. Chem. 18, 505–509 (2003)

    Article  Google Scholar 

  47. Fenton, R.R.; Gauci, R.; Junk, P.C.; Lindoy, L.F.; Luckay, R.C.; Meehan, G.V.; Price, J.R.; Turner, P.; Wei, G.: Macrocyclic ligand design. Structure–function relationships involving the interaction of pyridinyl-containing, mixed oxygen–nitrogen donor macrocycles with cobalt (II), nickel (II), copper (II), zinc (II), cadmium (II), silver (I) and lead (II). J. Chem. Soc. Dalton Trans. 10, 2185–2193 (2002)

    Article  Google Scholar 

  48. Khan, T.; Ahmad, R.; Azad, I.; Raza, S.; Joshi, S.; Khan, A.R.: Computer-aided drug design and virtual screening of targeted combinatorial libraries of mixed-ligand transition metal complexes of 2-butanone thiosemicarbazone. Comput. Biol. Chem. 75, 178–195 (2018)

    Article  Google Scholar 

  49. Alkhamis, K.; Alkhatib, F.; Alsoliemy, A.; Alrefaei, A.F.; Katouah, H.A.; Osman, H.E.; Mersal, G.A.; Zaky, R.; El-Metwaly, N.M.: Elucidation for coordination features of hydrazide ligand under influence of variable anions in bivalent transition metal salts; green synthesis, biological activity confirmed by in-silico approaches. J. Mol. Struct. 1238, 130410 (2021)

    Article  Google Scholar 

  50. Abu-Dief, A.M.; El-khatib, R.M.; Aljohani, F.S.; Alzahrani, S.O.; Mahran, A.; Khalifa, M.E.; El-Metwaly, N.M.: Synthesis and intensive characterization for novel Zn (II), Pd (II), Cr (III) and VO (II)-Schiff base complexes; DNA-interaction, DFT, drug-likeness and molecular docking studies. J. Mol. Struct. 1242, 130693 (2021)

    Article  Google Scholar 

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Acknowledgements

Dr. Mohamed acknowledges Taif University Researchers Supporting Project number (TURSP-2020/43). Taif University, Taif, Saudi Arabia.

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Authors and Affiliations

  1. Department of Chemistry, College of Science, University of Tabuk, Tabuk, Saudi Arabia

    Kholood Alkhamis & Nada M. Alatawi

  2. Department of Chemistry, Faculty of Applied Science, Umm Al Qura University, Makkah, Saudi Arabia

    Amerah Alsoliemy, Jihan Qurban, Arwa Alharbi & Nashwa M. El-Metwaly

  3. Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia

    Mohamed E. Khalifa

  4. Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt

    Rania Zaky & Nashwa M. El-Metwaly

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  1. Kholood Alkhamis
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  2. Nada M. Alatawi
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  3. Amerah Alsoliemy
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  4. Jihan Qurban
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Correspondence to Nashwa M. El-Metwaly.

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Alkhamis, K., Alatawi, N.M., Alsoliemy, A. et al. Synthesis and Investigation of Bivalent Thiosemicarbazone Complexes: Conformational Analysis, Methyl Green DNA Binding and In-silico Studies. Arab J Sci Eng 48, 273–290 (2023). https://doi.org/10.1007/s13369-022-06941-z

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