Journal of Fluorescence

, Volume 26, Issue 5, pp 1825–1837 | Cite as

Influence of Amino Acid-Nucleobase Hybrid Ligand in Binding and Biological Activity of Co(II) and Zn(II) Complexes

  • V. Violet Dhayabaran
  • T. Daniel Prakash


Synthesis of new metallic complex of cobalt and zinc with amino acid-nucleobase hybrid ligand have been achieved by simple chemical reaction of metal salt with amino acid L-histidine and nucleobase adenine as ligands. Various physicochemical techniques such as elemental analysis, conductometric measurements, FT-IR, UV-visible, 1H & 13C NMR, mass spectroscopy and magnetic measurements were employed to characterize the complexes. The results confirmed the formation of the ligand and the complex. The interaction of the complex with calf thymus DNA (CT-DNA) has been carried out using UV-visible titration, fluorescence spectroscopy, cyclic voltammetry and viscosity measurements. The intrinsic binding constant (Kb) and Stern-Volmer constant (Ksv) of the complexes have been calculated. The cleavage activity of the ligand and the complexes with pBR322 DNA was further confirmed by gel electrophoretic technique. The pharmacological activity of the ligand and the complexes was investigated by antioxidant, antimicrobial and cytotoxic activity, and they show promising pharmacological effect. The results of the molecular docking studies of the ligand and the complexes reinforce all the above facts.


Co(II) complex Zn(II) complex Adenine Histidine DNA interaction Pharmacological effect 



The authors thank the Principal, Management and Head of the Department of Chemistry, Head of the Department of Zoology Bishop Heber College, Trichy for providing necessary research facilities. The authors also gratefully acknowledge UGC, New Delhi for providing financial assistance under major research project (UGC File No. 42-238/2013 (SR)) to accomplish the work successfully.

Supplementary material

10895_2016_1874_MOESM1_ESM.docx (753 kb)
ESM 1 (DOCX 753 kb)


  1. 1.
    Abdel-Rahman LH, El-Khatib RM, Nassr LA, Abu-Dief AM, Lashin FE (2013) Design, characterization, teratogenicity testing, antibacterial, antifungal and DNA interaction of few high spin Fe (II) Schiff base amino acid complexes. Spectrochim Acta A 111:266–276CrossRefGoogle Scholar
  2. 2.
    Wang PH, Keck JG, Lien EJ, Lai MM (1990) Design, synthesis, testing, and quantitative structure-activity relationship analysis of substituted salicylaldehyde Schiff bases of 1-amino-3-hydroxyguanidine tosylate as new antiviral agents against coronavirus. J Med Chem 33(2):608–614CrossRefPubMedGoogle Scholar
  3. 3.
    Mai JC, Mi Z, Kim SH, Ng B, Robbins PD (2001) A proapoptotic peptide for the treatment of solid tumors. Cancer Research Cancer Res 61(21):7709–7712PubMedGoogle Scholar
  4. 4.
    Risso A, Braidot E, Sordano MC, Vianello A, Macrì F, Skerlavaj B, Zanetti M, Gennaro R, Bernardi P (2002) BMAP-28, an antibiotic peptide of innate immunity, induces cell death through opening of the mitochondrial permeability transition pore. Mol Cell Boil 22(6):1926–1935CrossRefGoogle Scholar
  5. 5.
    Cruciani RA, Barker JL, Zasloff M, Chen HC, Colamonici O (1991) Antibiotic magainins exert cytolytic activity against transformed cell lines through channel formation. P Natl Acad Sci USA 88(9):3792–3796CrossRefGoogle Scholar
  6. 6.
    Hatse S, Naesens L, Degréve B, Segers C, Vandeputte M, Waer M, Clercq ED, Balzarini J (1998) Potent antitumor activity of the acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl) adenine in choriocarcinoma-bearing rats. Int J Cancer 76(4):595–600CrossRefPubMedGoogle Scholar
  7. 7.
    Ghosh PK, Mandal HK, Mahapatra A (2010) Interaction of adenine with dichloro-[1-alkyl-2-(naphthylazo)-imidazole] palladium (II) complexes: kinetic and mechanistic studies. Transit Metal Chem 35(6):679–687CrossRefGoogle Scholar
  8. 8.
    Mesu JG, Visser T, Soulimani F, Weckhuysen BM (2005) Infrared and Raman spectroscopic study of pH-induced structural changes of L-histidine in aqueous environment. Vib Spectrosc 39(1):114–325CrossRefGoogle Scholar
  9. 9.
    Remko M, Fitz D, Rode BM (2010) Effect of metal ions (Li+, Na+, K+, Mg2+, Ca2+, Ni2+, Cu2+ and Zn2+) and water coordination on the structure and properties of l-histidine and zwitterionic l-histidine. Amino Acids 39(5):1309–1319CrossRefPubMedGoogle Scholar
  10. 10.
    Song YM, Wu Q, Yang PJ, Luan NN, Wang LF, Liu YM (2006) DNA Binding and cleavage activity of Ni (II) complex with all-trans retinoic acid. J Inorg Biochem 100(10):1685–1691CrossRefPubMedGoogle Scholar
  11. 11.
    Tan J, Wang B, Zhu L (2009) DNA binding, cytotoxicity, apoptotic inducing activity, and molecular modeling study of quercetin zinc (II) complex. Bioorgan Med Chem 17(2):614–620CrossRefGoogle Scholar
  12. 12.
    Friedman AE, Chambron JC, Sauvage JP, Turro NJ, Barton JK (1990) A molecular light switch for DNA: Ru (bpy) 2 (dppz) 2+. J Am Chem Soc 112(12):4960–4962CrossRefGoogle Scholar
  13. 13.
    Metcalfe C, JA T (2003) Kinetically inert transition metal complexes that reversibly bind to DNA. Chem Soc Rev 32(4):215–224CrossRefPubMedGoogle Scholar
  14. 14.
    Van Rijt SH, Sadler PJ (2009) Current applications and future potential for bioinorganic chemistry in the development of anticancer drugs. Drug Discov Today 14(23):1089–1097CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Reddy PR, Radhika M, Rao KS (2004) Interaction of zinc and cobalt with dipeptides and their DNA binding studies. J Chem Sci 116(4):221–226CrossRefGoogle Scholar
  16. 16.
    Reddy PR, Radhika M, Manjula P (2005) Synthesis and characterization of mixed ligand complexes of Zn (II) and Co (II) with amino acids: Relevance to zinc binding sites in zinc fingers. J Chem Sci 117(3):239–246CrossRefGoogle Scholar
  17. 17.
    Bandyopadhyay S, Mukherjee GN, Drew MG (2006) Equilibrium studies on mixed ligand complex formation of Co (II), Ni (II), Cu (II) and Zn (II) with N-(2-hydroxybenzyl)-l-histidine (H 2 hb-l-his) and typical N, N donor ligands: Crystal structure of [Ni (hb-l-his)(bipyridine)]· H 2 O complex. Inorg Chim Acta 359(10):3243–3251CrossRefGoogle Scholar
  18. 18.
    Wang YF, Li RF, Wang QL, LH Y, Yang GM, Liao DZ (2004) Synthesis, structure and properties of two bimetallic compounds [Co (bpy) 2 (NiL)](ClO4) 2 and {[Co (phen) 3](NiL)}(ClO4) 2 containing a macrocyclic oxamide ligand. Transit Metal Chem 29(7):728–731CrossRefGoogle Scholar
  19. 19.
    Perrin DD, Armarego WL, Perrin DR (1980) Purification of Laboratory Chemicals, 2nd edn. Pergamon Press, OxfordGoogle Scholar
  20. 20.
    Marmur J (1961) A procedure for the isolation of deoxyribonucleic acid from micro-organisms. J Mol Biol 3(2):208–IN1CrossRefGoogle Scholar
  21. 21.
    Eriksson M, Leijon M, Hiort C, Norden B, Graeslund A (1994) Binding of DELTA.-and LAMBDA.-[Ru (phen) 3] 2+ to [d (CGCGATCGCG)] 2 studied by NMR. Biochemistry-US 33(17):5031–5040CrossRefGoogle Scholar
  22. 22.
    Xiong Y, He XF, Zou XH, JZ W, Chen XM, Ji LN, Li RH, Zhou JY, Yu KB (1999) Interaction of polypyridyl ruthenium (II) complexes containing non-planar ligands with DNA. Dalton Trans (1):19–24Google Scholar
  23. 23.
    Sabolová D, Kožurková M, Plichta T, Ondrušová Z, Hudecová D, Šimkovič M, Paulíková H, Valent A (2011) Interaction of a copper (II)–Schiff base complexes with calf thymus DNA and their antimicrobial activity. Int J Biol Macromol 48(2):319–325CrossRefPubMedGoogle Scholar
  24. 24.
    Vujčić M, Tufegdžić S, Vujčić Z, Gašić MJ, Sladić D (2007) Interactions of the anti-tumor sesquiterpene hydroquinone avarol with DNA in vitro. J Serb Chem Soc 72(12):1265–1269CrossRefGoogle Scholar
  25. 25.
    Yoon I, Park HS, Cui BC, Li JZ, Kim JH, Lkhagvadulam B, Shim YK (2011) Photodynamic and Antioxidant Activities of Divalent Transition Metal Complexes of Methyl Pheophorbide-a. B Kor Chem Soc 32(spc8):2981–2987CrossRefGoogle Scholar
  26. 26.
    Arjmand F, Jamsheera A, Mohapatra DK (2013) Synthesis, characterization and in vitro DNA binding and cleavage studies of Cu (II)/Zn (II) dipeptide complexes. J Photoch Photobio B 121:75–85CrossRefGoogle Scholar
  27. 27.
    Ghose R (1992) Metal complexation with adenine and thymine. Synth React Inorg Met-Org Chem 22(4):379–392CrossRefGoogle Scholar
  28. 28.
    Raman N, Mahalakshmi R, Arun T, Packianathan S, Rajkumar R (2014) Metal based pharmacologically active complexes of Cu (II), Ni (II) and Zn (II): Synthesis, spectral, XRD, antimicrobial screening, DNA interaction and cleavage investigation. J Photoch Photobio B 138:211–222CrossRefGoogle Scholar
  29. 29.
    Zafar H, Kareem A, Sherwani A, Mohammad O, Ansari MA, Khan HM, Khan TA (2015) Synthesis and characterization of Schiff base octaazamacrocyclic complexes and their biological studies. J Photoch Photobio B 142:8–19CrossRefGoogle Scholar
  30. 30.
    Kumar GS, Ali MA, Choon TS, Prasad KJR (2016) Synthesis, DNA binding and cytotoxic evaluation of aminoquinoline scaffolds. J Chem Sci 128(3):391–400CrossRefGoogle Scholar
  31. 31.
    Costes JP, Dahan F, Laurent JP, Drillon M (1999) An alternating copper (II) chain with bridging oxamidato and nitrito ligands: crystal structure and magnetic properties of [Cu (NO 2) 2 CuL] n (L = N, N′-bis (2-methyl-2-aminopropyl) oxamide). Inorg Chim Acta 294(1):8–13CrossRefGoogle Scholar
  32. 32.
    Zheng K, Liu X, Deng H, Chao H, Yun F, Ji L (2003) Theoretical and experimental studies on electron transfer among complexes [M (phen) 3] 2 + [M = Os (II), Ru (II), Co (III) and Zn (II)] binding to DNA. J Mol Struc -THEOCHEM 626(1):295–304CrossRefGoogle Scholar
  33. 33.
    Wang XL, Chao H, Hong XL, Liu YJ, Ji LN (2005) Bis (2, 2′-bipyridine) cobalt (III) complexes containing asymmetric ligands: Synthesis, DNA-binding and photocleavage studies. Transit Metal Chem 30(3):305–311CrossRefGoogle Scholar
  34. 34.
    Waring MJ (1965) Complex formation between ethidium bromide and nucleic acids. J Mol Biol 13(1):269–282CrossRefPubMedGoogle Scholar
  35. 35.
    Nohara A, Umetani T, Sanno Y (1973) A facile synthesis of chromone-3-carboxaldehyde, chromone-3-carboxylic acid and 3-hydroxymethylchromone. Tetrahedron Lett 14(22):1995–1998CrossRefGoogle Scholar
  36. 36.
    Wang BD, Yang ZY, Li TR (2006) Synthesis, characterization, and DNA-binding properties of the Ln (III) complexes with 6-hydroxy chromone-3-carbaldehyde-(2′-hydroxy) benzoyl hydrazone. Bioorgan Med Chem 14(17):6012–6021CrossRefGoogle Scholar
  37. 37.
    Yang ZY, Wang BD, Li YH (2006) Study on DNA-binding properties and cytotoxicity in L 1210 of La (III) complex with PMBP-isonicotinoyl hydrazone. J Organomet Chem 691(20):4159–4166CrossRefGoogle Scholar
  38. 38.
    Nagaraj K, Velmurugan G, Sakthinathan S, Venuvanalingam P, Arunachalam S (2014) Influence of self-assembly on intercalative DNA binding interaction of double-chain surfactant Co (iii) complexes containing imidazo [4, 5-f][1, 10] phenanthroline and dipyrido [3, 2-d: 2′-3′-f] quinoxaline ligands: experimental and theoretical study. Dalton Trans 43(48):18074–18086CrossRefPubMedGoogle Scholar
  39. 39.
    Cory M, McKee DD, Kagan J, Henry DW, Miller JA (1985) Design, synthesis, and DNA binding properties of bifunctional intercalators. Comparison of polymethylene and diphenyl ether chains connecting phenanthridine. J Am Chem Soc 107(8):2528–2536CrossRefGoogle Scholar
  40. 40.
    Carter MT, Bard AJ (1987) Voltammetric studies of the interaction of tris (1, 10-phenanthroline) cobalt (III) with DNA. J Am Chem Soc 109(24):7528–7530CrossRefGoogle Scholar
  41. 41.
    Satyanarayana S, Dabrowiak JC, Chaires JB (1993) Tris (phenanthroline) ruthenium (II) enantiomer interactions with DNA: mode and specificity of binding. Biochemistry-US 32(10):2573–2584CrossRefGoogle Scholar
  42. 42.
    Tabassum S, Zaki M, Arjmand F, Ahmad I (2012) Synthesis of heterobimetallic complexes: In vitro DNA binding, cleavage and antimicrobial studies. J Photoch Photobio B 114:108–118CrossRefGoogle Scholar
  43. 43.
    Škerget M, Kotnik P, Hadolin M, Hraš AR, Simonič M, Knez Ž (2005) Phenols, proanthocyanidins, flavones and flavonols in some plant materials and their antioxidant activities. Food Chem 89(2):191–198CrossRefGoogle Scholar
  44. 44.
    Thankamony M, Mohanan K (2007) Synthesis, spectral studies, thermal decomposition kinetics, reactivity and antibacterial activity of some lanthanide (III) nitrate complexes of 2-(N-indole-2-one) amino-3-carboxyethyl-4, 5, 6, 7-tetrahydrobenzo-(b) thiophene. Indian J Chem A 46(2):247Google Scholar
  45. 45.
    Raman N, Raja JD, Sakthivel A (2007) Synthesis, spectral characterization of Schiff base transition metal complexes: DNA cleavage and antimicrobial activity studies. J Chem Sci 119(4):303–310CrossRefGoogle Scholar
  46. 46.
    Rohs R, Bloch I, Sklenar H, Shakked Z (2005) Molecular flexibility in ab initio drug docking to DNA: binding-site and binding-mode transitions in all-atom Monte Carlo simulations. Nucleic Acids Res 33(22):7048–7057CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.PG and Research Department of ChemistryBishop Heber College (Autonomous)TiruchirappalliIndia

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