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Two Cu(I) complexes based on semicarbazone ligand: synthesis, crystal structure, Hirshfeld surface and anticancer activity evaluation against human cell lines

  • Pedro H. O. Santiago
  • Mahmi Fujimori
  • Marcio A. S. Chagas
  • Eduardo L. França
  • Adenilda C. Honorio-França
  • Claudia C. GattoEmail author
Original Research

Abstract

Two novel Cu(I) complexes with the 2-acetylpyridine-N(4)-phenyl semicarbazone (HL) ligand, [CuCl (HL)(PPh3)]∙CH3CN (1) and [CuBr (HL)(PPh3)] (2), were investigated by single-crystal X-ray analysis, Hirshfeld surface, and physicochemical and spectroscopic methods. In both cases, the Schiff base was coordinated by the bidentate ligand via the pyridine nitrogen and the iminic nitrogen atoms. A molecule of triphenylphosphine and a halide ion (Cl or Br) completed the coordination sphere of the metal centers. The geometry around the copper atoms was distorted tetrahedral geometry. The secondary coordination sphere of Cu(I) is pentacoordinated and has weak interactions Cu···O of 2.906(1) Å and 2.783(1) Å. The 3D Hirshfeld surface and the 2D fingerprint plots of the complexes were analyzed quantitatively to verify the presence of intermolecular interactions. By their crystal structure of (2), it is possible to observe π···π stacking interactions between the pyridyl and phenyl rings from HL and also between phenyl rings and the triphenylphosphine ligands forming a 1D network. The biological activity of the Cu(I) salts, the free semicarbazone, and its Cu(I) complexes was evaluated against human cancer cell lines MCF-7 and nontumor cell lines PBMC.

Keywords

Copper(I) complexes Semicarbazone Crystal structure Hirshfeld surface Cytotoxicity 

Notes

Acknowledgments

All funding agencies are acknowledged for partial financial support.

Funding sources

The authors wish to thank FAPDF (process number 0193.001545/2017). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001, FINEP/CTINFRA, CNPq and DPP-UnB.

Author contributions

The manuscript was written with contributions from all authors. All authors have approved the final version of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

11224_2019_1379_MOESM1_ESM.cif (965 kb)
ESM 1 (CIF 964 kb)
11224_2019_1379_MOESM2_ESM.cif (1.1 mb)
ESM 2 (CIF 1110 kb)

References

  1. 1.
    Beraldo H (2004) Semicarbazonas e tiossemicarbazonas: O amplo perfil farmacológico e usos clínicos. Quim Nova 27:461–471.  https://doi.org/10.1590/S0100-40422004000300017 CrossRefGoogle Scholar
  2. 2.
    Beraldo H, Gambino D (2004) The wide pharmacological versatility of semicarbazones, thiosemicarbazones and their metal complexes. Mini Rev Med Chem 4:31–39.  https://doi.org/10.2174/1389557043487484 CrossRefGoogle Scholar
  3. 3.
    Patel RN, Shukla KK, Singh A et al (2009) Copper (II) complexes as superoxide dismutase mimics: synthesis, characterization, crystal structure and bioactivity of copper (II) complexes. Inorg Chim Acta 362:4891–4898.  https://doi.org/10.1016/j.ica.2009.07.037 CrossRefGoogle Scholar
  4. 4.
    Machado I, Fernández S, Becco L et al (2014) New fac -tricarbonyl rhenium(I) semicarbazone complexes : synthesis , characterization , and biological evaluation. J Coord Chem 67:1835–1850CrossRefGoogle Scholar
  5. 5.
    Nadella S, Selvakumar PM, Suresh E et al (2012) Lanthanide (III) complexes of bis-semicarbazone and bis-imine-substituted phenanthroline ligands: solid-state structures, photophysical properties, and anion sensing. Chem A Eur J 18:16784–16792.  https://doi.org/10.1002/chem.201201705 CrossRefGoogle Scholar
  6. 6.
    Farhadi S, Amini MM, Dusek M et al (2017) A new nanohybrid material constructed from Keggin-type polyoxometalate and Cd (II) semicarbazone Schiff base complex with excellent adsorption properties for the removal of cationic dye pollutants. J Mol Struct 1130:592–602.  https://doi.org/10.1016/j.molstruc.2016.10.081 CrossRefGoogle Scholar
  7. 7.
    Farhadi S, Mahmoudi F, Dusek M et al (2017) A new inorganic–organic nanohybrid based on a copper (II) semicarbazone complex and the PMo12O403−polyanion: synthesis, characterization, crystal structure and photocatalytic activity for degradation of cationic dyes. Polyhedron 122:247–256.  https://doi.org/10.1016/j.poly.2016.11.034 CrossRefGoogle Scholar
  8. 8.
    Singh HL, Singh JB, Bhanuka S (2016) Synthesis, spectral, DFT, and antimicrobial studies of tin (II) and lead (II) complexes with semicarbazone and thiosemicarbazones derived from (2-hydroxyphenyl)(pyrrolidin-1-yl)methanone. J Coord Chem 69:343–353.  https://doi.org/10.1080/00958972.2015.1115485 CrossRefGoogle Scholar
  9. 9.
    Fernández M, Becco L, Correia I et al (2013) Oxidovanadium (IV) and dioxidovanadium(V) complexes of tridentate salicylaldehyde semicarbazones: searching for prospective antitrypanosomal agents. J Inorg Biochem 127:150–160.  https://doi.org/10.1016/j.jinorgbio.2013.02.010 CrossRefGoogle Scholar
  10. 10.
    Singh HL, Singh JB, Bhanuka S (2016) Synthesis, spectroscopic characterization, biological screening, and theoretical studies of organotin (IV) complexes of semicarbazone and thiosemicarbazones derived from (2-hydroxyphenyl)(pyrrolidin-1-yl)methanone. Res Chem Intermed 42:997–1015.  https://doi.org/10.1007/s11164-015-2069-3 CrossRefGoogle Scholar
  11. 11.
    Gambino D, Fernández M, Santos D et al (2011) Searching for gallium bioactive compounds: gallium (III) complexes of tridentate salicylaldehyde semicarbazone derivatives. Polyhedron 30:1360–1366.  https://doi.org/10.1016/j.poly.2011.02.037 CrossRefGoogle Scholar
  12. 12.
    Chen H, Ma XQ, Lv YY et al (2016) Four transition metal complexes with a semicarbazone ligand bearing pyrazine unit. J Mol Struct 1109:146–153.  https://doi.org/10.1016/j.molstruc.2015.12.014 CrossRefGoogle Scholar
  13. 13.
    Denoyer D, Masaldan S, La Fontaine S, Cater MA (2015) Targeting copper in cancer therapy: “Copper That Cancer”. Metallomics 7:1459–1476.  https://doi.org/10.1039/C5MT00149H CrossRefGoogle Scholar
  14. 14.
    Duncan C, White AR (2012) Copper complexes as therapeutic agents. Metallomics 4:127–138.  https://doi.org/10.1039/C2MT00174H CrossRefGoogle Scholar
  15. 15.
    Krishnamoorthy P, Sathyadevi P, Butorac RR et al (2012) Copper(i) and nickel (ii) complexes with 1 : 1 vs. 1 : 2 coordination of ferrocenyl hydrazone ligands: do the geometry and composition of complexes affect DNA binding/cleavage, protein binding, antioxidant and cytotoxic activities? Dalt Trans 41:4423.  https://doi.org/10.1039/c2dt11938b CrossRefGoogle Scholar
  16. 16.
    Leovac VM, Rodic MV, Jovanovic LS et al (2015) Transition metal complexes with 1-adamantoyl hydrazones - cytotoxic copper (II) complexes of tri- and tetradentate pyridine chelators containing an adamantane ring system. Eur J Inorg Chem 2015:882–895.  https://doi.org/10.1002/ejic.201403050 CrossRefGoogle Scholar
  17. 17.
    Hancock CN, Stockwin LH, Han B et al (2011) A copper chelate of thiosemicarbazone NSC 689534 induces oxidative/ER stress and inhibits tumor growth in vitro and in vivo. Free Radic Biol Med 50:110–121.  https://doi.org/10.1016/j.freeradbiomed.2010.10.696 CrossRefGoogle Scholar
  18. 18.
    Li MX, Zhang LZ, Chen CL et al (2012) Synthesis, crystal structures, and biological evaluation of Cu (II) and Zn (II) complexes of 2-benzoylpyridine Schiff bases derived from S-methyl- and S-phenyldithiocarbazates. J Inorg Biochem 106:117–125.  https://doi.org/10.1016/j.jinorgbio.2011.09.034 CrossRefGoogle Scholar
  19. 19.
    Sathyadevi P, Krishnamoorthy P, Butorac RR et al (2012) Synthesis of novel heterobimetallic copper(i) hydrazone Schiff base complexes: a comparative study on the effect of heterocyclic hydrazides towards interaction with DNA/protein, free radical scavenging and cytotoxicity. Metallomics 4:498.  https://doi.org/10.1039/c2mt00004k CrossRefGoogle Scholar
  20. 20.
    Lee WY, Lee PPF, Yan YK, Lau M (2010) Cytotoxic copper (II) salicylaldehyde semicarbazone complexes: mode of action and proteomic analysis. Metallomics 2:694–705.  https://doi.org/10.1039/c0mt00016g CrossRefGoogle Scholar
  21. 21.
    Munira Haidad Ali S, Yan Y-K, Lee PPF et al (2014) Copper (II) complexes of substituted salicylaldehyde dibenzyl semicarbazones: synthesis, cytotoxicity and interaction with quadruplex DNA. Dalt Trans 43:1449–1459.  https://doi.org/10.1039/c3dt52297k CrossRefGoogle Scholar
  22. 22.
    Raja DS, Bhuvanesh NSP, Natarajan K (2011) Duraisamy Senthil Raja, † Nattamai S. P. Bhuvanesh, ‡ and Karuppannan Natarajan †, * † ‡. Inorg ChemGoogle Scholar
  23. 23.
    Gatto CC, Miguel PM, Almeida CM et al (2017) A copper (II) complex of a semicarbazone: crystal structure, spectroscopic analysis and cytotoxicity against human cancer cell lines. Transit Met Chem 42:503–508.  https://doi.org/10.1007/s11243-017-0154-8 CrossRefGoogle Scholar
  24. 24.
    Gatto CC, Lima IJ, Chagas MAS (2017) Supramolecular architectures and crystal structures of gold (III) compounds with semicarbazones. Supramol Chem 29:296–307.  https://doi.org/10.1080/10610278.2016.1227440 CrossRefGoogle Scholar
  25. 25.
    Makanova D, Ondrejovic G, Gazo J (1973) Reaktionen des Kupfer ( H ) - chlorids mit Triphenylphosphin Isolierung und Identifizierung einiger Oxidoreduktionsprodukte. Chem Zvesti 27:4–13Google Scholar
  26. 26.
    Aiswarya N, Sithambaresan M, Kurup MRP, Ng SW (2013) Dichlorido{2-[( E )-phenyl (pyridin-2-yl-κ N )methylidene]- N -phenylhydrazinecarboxamide-κ 2 N 2 , O }copper (II). Acta Crystallogr Sect E Struct Rep Online 69:m588–m589.  https://doi.org/10.1107/S1600536813026883 CrossRefGoogle Scholar
  27. 27.
    (1999) SMART and SAINT. Area Detector Control Integration SoftwareGoogle Scholar
  28. 28.
    Sheldrick GM (1997) SADABS, program for empirical absorption correction of area detector dataGoogle Scholar
  29. 29.
    Sheldrick GM (2007) A short history of SHELX. Acta Crystallogr Sect A Found Crystallogr 64:112–122.  https://doi.org/10.1107/S0108767307043930 CrossRefGoogle Scholar
  30. 30.
    Sheldrick GM (2015) Crystal structure refinement with SHELXL. Acta Crystallogr Sect C Struct Chem 71:3–8.  https://doi.org/10.1107/S2053229614024218 CrossRefGoogle Scholar
  31. 31.
    Dolomanov OV, Bourhis LJ, Gildea RJ et al (2009) OLEX2: a complete structure solution, refinement and analysis program. J Appl Crystallogr 42:339–341.  https://doi.org/10.1107/S0021889808042726 CrossRefGoogle Scholar
  32. 32.
    McKinnon JJ, Spackman MA, Mitchell AS (2004) Novel tools for visualizing and exploring intermolecular interactions in molecular crystals. Acta Crystallogr Sect B B60:627–668.  https://doi.org/10.1107/S0108768104020300 CrossRefGoogle Scholar
  33. 33.
    Spackman MA, Jayatilaka D (2009) Hirshfeld surface analysis. CrystEngComm 11:19–32.  https://doi.org/10.1039/b818330a CrossRefGoogle Scholar
  34. 34.
    Turner MJ, McKinnon JJ, Wolff SK, et al (2017) CrystalExplorer17Google Scholar
  35. 35.
    Honorio-França AC, Hara CCP, Ormonde JVS et al (2013) Human colostrum melatonin exhibits a day-night variation and modulates the activity of colostral phagocytes. J Appl Biomed 11:153–162.  https://doi.org/10.2478/v10136-012-0039-2 CrossRefGoogle Scholar
  36. 36.
    Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63.  https://doi.org/10.1016/0022-1759(83)90303-4 CrossRefGoogle Scholar
  37. 37.
    Osti RZ, Serrano FA, Paschoalin T et al (2012) The in vitro and in vivo antitumour activities of nitrosyl ruthenium amine complexes. Aust J Chem 65:1333–1341CrossRefGoogle Scholar
  38. 38.
    Recio Despaigne AA, Da Silva JG, Do Carmo ACM et al (2009) Copper (II) and zinc (II) complexes with 2-benzoylpyridine-methyl hydrazone. J Mol Struct 920:97–102.  https://doi.org/10.1016/j.molstruc.2008.10.025 CrossRefGoogle Scholar
  39. 39.
    Despaigne AAR, da SJG, do Carmo ACM et al (2009) Copper (II) and zinc (II) complexes with 2-formylpyridine-derived hydrazones. Polyhedron 28:3797–3803.  https://doi.org/10.1016/j.poly.2009.07.059 CrossRefGoogle Scholar
  40. 40.
    Shaabani B, Khandar AA, Mahmoudi F et al (2013) Novel binuclear cu (II) complexes combining a semicarbazone Schiff base with distinct bridging ligands: structure and antimicrobial activity. Polyhedron 57:118–126.  https://doi.org/10.1016/j.poly.2013.04.016 CrossRefGoogle Scholar
  41. 41.
    Hosseini-Monfared H, Bikas R, Szymczak R et al (2013) Syntheses, crystal structures and magnetic studies of new copper (II) complexes of (E)-N′-(phenyl (pyridin-2-yl)methylene) isonicotinohydrazide containing azide and SCN anions. Polyhedron 63:74–82.  https://doi.org/10.1016/j.poly.2013.06.055 CrossRefGoogle Scholar
  42. 42.
    Okuniewski A, Rosiak D, Chojnacki J, Becker B (2015) Coordination polymers and molecular structures among complexes of mercury (II) halides with selected 1-benzoylthioureas. Polyhedron 90:47–57.  https://doi.org/10.1016/j.poly.2015.01.035 CrossRefGoogle Scholar
  43. 43.
    Pauling L (1929) The principles determining the structure of complex ionic crystals. J Am Chem Soc 51:1010–1026.  https://doi.org/10.1021/ja01379a006 CrossRefGoogle Scholar
  44. 44.
    Shields GP, Raithby PR, Allen FH, Motherwell WDS (2000) The assignment and validation of metal oxidation states in the Cambridge Structural Database. Acta Crystallogr Sect B 56:455–465.  https://doi.org/10.1107/S0108768199015086 CrossRefGoogle Scholar
  45. 45.
    Gholivand K, Farshadfar K, Roe SM et al (2016) Investigation of structure-directing interactions within copper(I) thiocyanate complexes through X-ray analyses and non-covalent interaction (NCI) theoretical approach. CrystEngComm 18:7104–7115.  https://doi.org/10.1039/C6CE01339B CrossRefGoogle Scholar
  46. 46.
    Gholivand K, Farshadfer K, Roe SM et al (2016) Structural and photophysical characterization of mono- and binuclear Cu(I) complexes based on carbohydrazones: a combined experimental and computational study. CrystEngComm 18:2873–2884.  https://doi.org/10.1039/c5ce02208h CrossRefGoogle Scholar
  47. 47.
    Janiak C (2000) A critical account on π–π stacking in metal complexes with aromatic nitrogen-containing ligands. J Chem Soc Dalt Trans 3885–3896.  https://doi.org/10.1039/b003010o

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory of Inorganic Synthesis and CrystallographyUniversity of Brasilia (IQ-UnB)BrasiliaBrazil
  2. 2.Institute of Biological and Health ScienceFederal University of Mato GrossoBarra do GarçasBrazil

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