Journal of Central South University

, Volume 22, Issue 5, pp 1619–1625 | Cite as

Synthesis, structure, DNA binding and cleavage activity of a new copper(II) complex of bispyridylpyrrolide

  • Rui Min (闵睿)
  • Xiao-hui Hu (胡晓惠)
  • Xiao-yi Yi (易小艺)Email author
  • Shou-chun Zhang (张寿春)Email author


A copper-bispyridylpyrrolide complex [Cu(PDPH)Cl] (PDPH = 2,5-bis(2′-pyridyl)pyrrole) was synthesized and characterized. The complex crystallizes in the orthorhombic system with space group Pccn, a = 0.9016(3) nm, b = 1.0931(4) nm, c = 2.5319(8) nm, and V = 2.4951(15) nm3. The copper center is situated in a square planar geometry. The interaction of the copper(II) complex with calf thymus DNA (CT-DNA) was investigated by electronic absorption, circular dichroism (CD) and fluorescence spectra. It is proposed that the complex binds to CT-DNA through groove binding mode. Nuclease activity of the complex was also studied by gel electrophoresis method. The complex can efficiently cleave supercoiled pBR322 DNA in the presence of ascorbate (H2A) via oxidative pathway. The preliminary mechanism of DNA cleavage by the complex with different inhibiting reagents indicates that the hydroxyl radicals were involved as the active species in the DNA cleavage process.

Key words

copper complex bispyridylpyrrolide DNA-binding DNA cleavage 


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  1. [1]
    JAMIESON E R, LIPPARD S J. Structure, recognition, and processing of cisplatin-DNA adducts [J]. Chemical Reviews, 1999, 99(9): 2467–2498.CrossRefGoogle Scholar
  2. [2]
    SIGMAN D S, MAZUMDER A, PERRIN D M. Chemical nucleases [J]. Chemical Reviews, 1993, 93(6): 2295–2316.CrossRefGoogle Scholar
  3. [3]
    TUREL I, KLJUN J. Interactions of metal ions with DNA, its constituents and derivatives, which may be relevant for anticancer research [J]. Current Topics in Medicinal Chemistry, 2011, 11(21): 2661–2687.CrossRefGoogle Scholar
  4. [4]
    GUO Zi-jian, SADLER P J. Metals in medicine [J]. Angewandte Chemie International Edition, 1999, 38(11): 1512–1531.CrossRefGoogle Scholar
  5. [5]
    JIANG Qin, XIAO Nan, SHI Peng-fei, ZHU Yang-guang, GUO Zi-jian. Design of artificial metallonucleases with oxidative mechanism [J]. Coordination Chemistry Reviews, 2007, 251(15): 1951–1972.CrossRefGoogle Scholar
  6. [6]
    GARBUTCHEON-SINGH K, GRANT M P, HARPER B W, KRAUSE-HEUER A M, MANOHAR M, ORKEY N, ALDRICH-WRIGHT J R. Transition metal based anticancer drugs [J]. Current Topics in Medicinal Chemistry, 2011, 11(5): 521–542.CrossRefGoogle Scholar
  7. [7]
    DESBOUIS D, TROITSKY I P, BELOUSOFF M J, SPICCIA L, GRAHAM B. Copper(II), zinc(II) and nickel(II) complexes as nuclease mimetics [J]. Coordination Chemistry Reviews, 2012, 256(11): 897–937.CrossRefGoogle Scholar
  8. [8]
    STRTER N, LIPSCOMB W N, KLABUNDE T, KREBS B. Two-metal ion catalysis in enzymatic acyl and phosphoryl-transfer reactions [J]. Angewandte Chemie International Edition in English, 1996, 35(18): 2024–2055.CrossRefGoogle Scholar
  9. [9]
    WILCOX D E. Binuclear metallohydrolases [J]. Chemical Reviews, 1996, 96(7): 2435–2458.CrossRefGoogle Scholar
  10. [10]
    SIGMAN D S, GRAHAM D R, AURORA V D, STERN A M. Oxygen-dependent cleavage of DNA by the 1, 10-phenanthroline. cuprous complex. Inhibition of Escherichia coli DNA polymerase I [J]. Journal of Biological Chemistry, 1979, 254(24): 12269–12272.Google Scholar
  11. [11]
    PATRA A K, DHAR S, NETHAJI M, CHAKRAVARTY A R. Metal-assisted red light-induced DNA cleavage by ternary L-methionine copper(II) complexes of planar heterocyclic bases [J]. Dalton Transactions, 2005(5): 896–902.Google Scholar
  12. [12]
    TERENZI A, TOMASELLO L, SPINELLO A, BRUNO G, GIORDANO C, BARONE G. (dipyrido 3,2-a:2′,3′-c] henazine) glycinato) copper(II) perchlorate: A novel DNA-intercalator with anti-proliferative activity against thyroid cancer cell lines [J]. Journal of Inorganic Biochemistry, 2012, 117: 103–110CrossRefGoogle Scholar
  13. [13]
    BALDINI M, BELICCHI-FERRARI M, BISCEGLIE F, DALL’AGLIO P P, PELOSI 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]. Inorganic Chemistry, 2004, 43(22): 7170–7179.CrossRefGoogle Scholar
  14. [14]
    GOMEZ-SAIZ P, GIL-GARCA R, MAESTRO M A, PIZARRO J L, ARRIORTUA M I, LEZAMA L, ROJO T, GONZALEZ-ALVAREZ M, BORRAS J, GARCIA-TOJAL J. Structure, magnetic properties and nuclease activity of pyridine-2-carbaldehyde thiosemicarbazone copper(II) complexes [J]. Journal of Inorganic Biochemistry, 2008, 102(10): 1910–1920.CrossRefGoogle Scholar
  15. [15]
    JAYAMANI A, THAMILARASAN V, SENGOTTUVELAN N, MANISANKAR P, KANG S W, KIM Y I, GANESAN V. Synthesis of mononuclear copper(II) complexes of acyclic Schiff’s base ligands: Spectral, structural, electrochemical, antibacterial, DNA binding and cleavage activity [J]. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2014, 122C: 365–374.CrossRefGoogle Scholar
  16. [16]
    KOU Ying-ying, TIAN Jin-lei, LI Dong-dong, GU Wen, LIU Xin, YAN Shi-ping, LI Ao, AI Zheng, CHENG Peng. Synthesis, structure, magnetic properties and DNA cleavage of binuclear Cu(II) Schiff-base complexes [J]. Dalton Transactions, 2009, 13: 2374–2382.CrossRefGoogle Scholar
  17. [17]
    LIU Jie, LU Tong-bu, DENG Hong, JI Liang-nian, QU Liang-hu, ZHOU Hui. Synthesis, DNA-binding and cleavage studies of macrocyclic copper(II) complexes [J]. Transition Metal Chemistry, 2003, 28(1): 116–121.CrossRefGoogle Scholar
  18. [18]
    HUANG Yu, CHEN Shan-yong, ZHANG Ji, TAN Xin-yu, JIANG Ning, HANG Jing-jing, ZHANG Yu, LIN Hong-hui, YU Xian-qi. Dinuclear copper(II) complexes of macrocyclic polyamines: Synthesis, characterization, and DNA cleavage [J]. Chemistry & Biodiversity, 2009, 6(4): 475–486.CrossRefGoogle Scholar
  19. [19]
    LIU H K, SADLER P J. Metal complexes as DNA intercalators [J]. Accounts of Chemical Research, 2011, 44(5): 349–359.CrossRefGoogle Scholar
  20. [20]
    MANIKANDAMATHAVAN V M, UNNI NAIR B. DNA binding and cytotoxicity of copper(II) imidazole terpyridine complexes: Role of oxyanion, hydrogen bonding and π-π interaction [J]. European Journal of Medicinal Chemistry, 2013, 68: 244–252.CrossRefGoogle Scholar
  21. [21]
    ZHANG Shou-chun, ZHU Yang-guang, TU Chao, WEI Hai-ying, YANG Zhen, LIN Li-ping, DING Jian, ZHANG Jun-feng, GUO Zi-jian. A novel cytotoxic ternary copper(II) complex of 1,10-phenanthroline and L-threonine with DNA nuclease activity [J]. Journal of Inorganic Biochemistry, 2004, 98(12): 2099–2106.CrossRefGoogle Scholar
  22. [22]
    ZHANG Shou-chun, ZHOU Jian-liang. Ternary copper(II) complex of 1,10-phenanthroline and L-glycine: Crystal structure and interaction with DNA [J]. Journal of Coordination Chemistry, 2008, 61(15): 2488–2498.CrossRefGoogle Scholar
  23. [23]
    ZHANG Shou-chun, CHUN Xiao-gai, CHEN Yun, ZHOU Jian-liang. Synthesis, Crystal structure and DNA cleavage activity of a ternary copper(II) complex of dipyrido [3,2-d:2′,3′-f]-quinoxaline and glycine [J]. Chinese Journal of Chemistry, 2011, 29(1): 65–71.CrossRefGoogle Scholar
  24. [24]
    PATEL M N, DOSI P A, BHATT B S. Antibacterial, DNA interaction and superoxide dismutase activity of drug based copper(II) coordination compounds [J]. Polyhedron, 2010, 29(17): 3238–3245.CrossRefGoogle Scholar
  25. [25]
    MANIKANDAMATHAVAN V M, RAJAPANDIAN V, FREDDY A J, WEYHERMULLER T, SUBRAMANIAN V, NAIR B U. Effect of coordinated ligands on antiproliferative activity and DNA cleavage property of three mononuclear Cu(II)-terpyridine complexes [J]. European Journal of Medicinal Chemistry, 2012, 57: 449–458.CrossRefGoogle Scholar
  26. [26]
    ALVAREZ N, VEIGA N, IGLESIAS S, TORRE M H, FACCHIN G. Synthesis, structural characterization and DNA interaction of new copper-terpyridine complexes [J]. Polyhedron, 2014, 68: 295–302.CrossRefGoogle Scholar
  27. [27]
    JONES R A, KARATZA M, VORO T N, CIVEIR P U, FRANCK A P, WILLIAMSON D J. Extended heterocyclic systems 1. The synthesis and characterisation of pyrrolylpyridines, alternating pyrrole: Pyridine oligomers and polymers, and related systems [J]. Tetrahedron, 1996, 52(26): 8707–8724.CrossRefGoogle Scholar
  28. [28]
    SHELDRICK G M. SADABS, program for empirical absorption correction of are detector data [M]. Germany: University of Göttingen, 1996.Google Scholar
  29. [29]
    SHELDRICK G M. SHELXTL version 5.10 [M]. Madison, Wisconsin, USA: Bruker AXS Inc, 1997Google Scholar
  30. [30]
    MARMUR J. A procedure for the isolation of deoxyribonucleic acid from micro-organisms [J]. Journal of Molecular Biology, 1961, 3(1): 208–218.CrossRefGoogle Scholar
  31. [31]
    REICHMANN M E, RICE S A, THOMAS C A, DOTY P. A further examination of the molecular weight and size of desoxypentose nucleic acid [J]. Journal of American Chemical Society, 1954, 76(11): 3047–3053.CrossRefGoogle Scholar
  32. [32]
    WOLFE A, SHIMER G H Jr, MEEHAN T. Polycyclic aromatic hydrocarbons physically intercalate into duplex regions of denatured DNA [J]. Biochemistry, 1987, 26(20): 6392–6396.CrossRefGoogle Scholar
  33. [33]
    HU Xiao-hui, LIANG Yan, LI Chen, YI Xiao-yi. Multi-nuclear silver(I) and copper(I) complexes: A novel bonding mode for bispyridylpyrrolides [J]. Dalton Transactions, 2014, 43(6): 2458–2464.CrossRefGoogle Scholar
  34. [34]
    IMLER G H, LU Z, KISTLER K A, CARROLL P J, WAYLAND B B, ZDILLA M J. Complexes of 2,5-bis(α-pyridyl) pyrrolate with Pd(II) and Pt(II): A monoanionic iso-π-electron ligand analog of terpyridine [J]. Inorganic Chemistry, 2012, 51(19): 10122–10128.CrossRefGoogle Scholar
  35. [35]
    BARTON J K, DANISHEFSKY A, GOLDBERG J. Tris (phenanthroline)ruthenium(II): Stereoselectivity in binding to DNA [J]. Journal of the American Chemical Society, 1984, 106(7): 2172–2176.CrossRefGoogle Scholar
  36. [36]
    NAIR R B, TENG E S, KIRKLAND S L, MURPHY C J. Synthesis and DNA-binding properties of [Ru(NH3)4dppz]2+ [J]. Inorganic Chemistry, 1998, 37(1): 139–141.CrossRefGoogle Scholar
  37. [37]
    WARING M J. Complex formation between ethidium bromide and nucleic acids [J]. Journal of Molecular Biology, 1965, 13(1): 269–282.CrossRefGoogle Scholar
  38. [38]
    COLLINS J G, SHIELDS T P, BARTON J K. 1H-NMR of Rh(NH3)4phi3+ bound to d(TGGCCA)2: Classical intercalation by a nonclassical octahedral metallointercalator [J]. Journal of the American Chemical Society, 1994, 116(22): 9840–9846.CrossRefGoogle Scholar
  39. [39]
    UMA MAHESWARI P, PALANIANDAVAR M. DNA binding and cleavage properties of certain tetrammine ruthenium(II) complexes of modified 1,10-phenanthrolines, effect of hydrogen-bonding on DNA-binding affinity [J]. Journal of Inorganic Biochemistry, 2004, 98(2): 219–230.CrossRefGoogle Scholar
  40. [40]
    UMA V, CASTINEIRAS A, NAIR B U. Copper(II) complexes of N4 tetradentate ligands with flexible alkyl spacers: Crystal structure, DNA binding and cleavage studies [J]. Polyhedron, 2007, 26(13): 3008–3016.CrossRefGoogle Scholar
  41. [41]
    SONG Yu-fei, YANG Pin. Mononuclear tetrapyrido [3,2-a:2′,3′-c:3″,2″-h:2′″,3′″-j] phenazine (tpphz) cobalt complex [J]. Polyhedron, 2001, 20(6): 501–506.CrossRefGoogle Scholar
  42. [42]
    BAGULEY B C. Nonintercalative DNA-binding antitumour compounds [J]. Molecular and Cellular Biochemistry, 1982, 43(3): 167–181.CrossRefGoogle Scholar
  43. [43]
    KRISHNA A G, KUMAR D V, KHAN B, RAWAL S, GANESH K N. Taxol-DNA interactions: Fluorescence and CD studies of DNA groove binding properties of taxol [J]. Biochimica et Biophysica Acta (BBA)-General Subjects, 1998, 1381(1): 104–112.CrossRefGoogle Scholar

Copyright information

© Central South University Press and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Rui Min (闵睿)
    • 1
  • Xiao-hui Hu (胡晓惠)
    • 1
  • Xiao-yi Yi (易小艺)
    • 1
    Email author
  • Shou-chun Zhang (张寿春)
    • 1
    Email author
  1. 1.School of Chemistry and Chemical EngineeringCentral South UniversityChangshaChina

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