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Synthesis, DNA-binding, Cytotoxicity, Photo Cleavage, Antimicrobial and Docking Studies of Ru(II) Polypyridyl Complexes

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Abstract

Three Ruthenium(II) polypyridine complexes, [Ru(phen)2(mipc)]2+(1), [Ru(bpy)2(mipc)]2+ (2) and [Ru(dmb)2(mipc)]2+(3) [mipc = 2-(6-methyl-3-(1H-imidazo[4, 5-f][1,10]-phenanthroline-2-yl)-4H-chromene-4-one, phen = 1,10-phenanthroline,bpy = 2, 2′bipyridine,dmb = 4, 4′-dimethyl-2, 2′-bipyridine] have been synthesized and characterized by elemental analysis, IR, UV–Vis, 1H& 13C NMR and mass spectra. The DNA-binding properties of the Ruthenium(II) complexes were investigated by spectrophotometric methods, viscosity measurements and light switch studies. These three complexes have been focused on photo activated cleavage studies with pBR-322 and antimicrobial studies. Experimental results indicate that the three complexes intercalate into DNA base pairs and follows the order of 1 > 2 > 3 respectively. Molecular docking studies also support the DNA interactions with complexes through hydrogen bonding and vander Waal’s interactions. Cytotoxicity studies with Hela cell lines has been revealing about anti tumor activity of these complexes.

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References

  1. Lippard SJ (1987) Chemistry and molecular biology of platinum anticancer drugs. Pure Appl Chem 59:731–742

    Article  CAS  Google Scholar 

  2. Salim A, Abu-Surrah MK (2006) Platinum Group Antitumor Chemistry: design and development of New Anticancer Drugs Complementary to Cisplatin. Curr Med Chem 13:1337–1357

    Article  Google Scholar 

  3. Zhang Z, Bi C, Schmitt SM, Fan Y, Dong L, Jian Zuo Q, Dou P (2012) 1, 10-Phenanthroline promotes copper complexes into tumor cells and induces apoptosis by inhibiting the proteasome activity. J Biol Inorg Chem 17(8):1257–1267

    Article  PubMed  CAS  Google Scholar 

  4. Giovagnini L, Ronconi L, Aldinucci D, Lorenzon D, Sitran S, Fregona D (2005) Synthesis, Characterization, and Comparative in Vitro Cytotoxicity Studies of Platinum(II), Palladium(II), and Gold(III) Methyl sarcosine dithiocarbamate Complexes. J Med Chem 48:1588–1595

    Article  PubMed  CAS  Google Scholar 

  5. Perez-Rebolledo A, DaniloAyala J, de Lima GM, Marchini N, Bombieri G, Zani CL, Souza-Fagundes EM, Beraldo H (2005) Structural studies and cytotoxic activity of N(4)-phenyl-2-benzoylpyridine thiosemicarbazone Sn(IV) complexes. Eur J Med Chem 40(5):467–472

    Article  PubMed  CAS  Google Scholar 

  6. Liu J, Zheng W, Shi S, Tan C, Chen J, Zheng K, Ji L (2008) Synthesis, antitumor activity and structure–activity relationships of a series of Ru(II) complexes. J Inorg Biochem 102:193

    Article  PubMed  CAS  Google Scholar 

  7. Liu Y-J, Liang Z-H, Li Z-Z, Yao J-H, Huang H-L (2011) Ruthenium(II) Polypyridyl Complexes: synthesis and Studies of DNA Binding, Photocleavage, Cytotoxicity, Apoptosis, Cellular Uptake, and Antioxidant Activity. DNA Cell Biol 30(10):829–838

    Article  PubMed  Google Scholar 

  8. Li X, Xie Y-Y, Zhong N-J, Liang Z-H, He J, Huang H-L, Liu Y-J (2012) DNA-binding and photocleavage, cytotoxicity, apoptosis and antioxidant activity studies of ruthenium(II) complexes. Transit Met Chem 37:197–205

    Article  Google Scholar 

  9. Puckett CA, Barton JK (2008) Mechanism of cellular uptake of a ruthenium polypyridyl complex. Biochem 47:11711–11716

    Article  CAS  Google Scholar 

  10. Sigel A, Sigel H Eds. (1996) Metal ions in biological systems, interaction of metal ions with nucleotides, nucleic acids, and their constituents. Marcel Dekker, New York 32– 854

  11. Pyle AM, Morii T, Barton JK (1990) Probing Microstructures in Double Helical DNA with Chiral Metal Complexes: recognition of Changes in Base-Pairs Propeller Twisting in Solution. J Am Chem Soc 112:9432

    Article  CAS  Google Scholar 

  12. Sigman DS, Mazumdre A, Perrin DM (1993) Chemical nucleases. Chem Rev 93:2295–2316

    Article  CAS  Google Scholar 

  13. Erkkila KE, Odom DT, Barton JK (1999) Recognition and Reaction of Metallointercalators with DNA. Chem Rev 99:2777

    Article  PubMed  CAS  Google Scholar 

  14. Ji LN, Zou XH, Liu JG (2001) Shape- and enantioselective interaction of Ru(II)/Co(III) polypyridyl complexes with DNA. Coord Chem Rev 513:216–217

    Google Scholar 

  15. Xiong Y, Ji LN (1999) Synthesis, DNA-binding and DNA-mediated luminescence quenching of Ru(II) polypyridine complexes. Coord Chem Rev 711:185–186

    Google Scholar 

  16. Pelligrini PP, Aldrich-Wright JR (2003) Evidence for chiral discrimination of ruthenium (II) polypyridyl complexes by DNA. Dalton Trans 3:176

    Article  Google Scholar 

  17. Lawrence D, Vaidyanathan VG, Nair BU (2006) Synthesis, characterization and DNA binding studies of two mixed ligand complexes of ruthenium (II). J Inorg Biochem 100:1244

    Article  PubMed  CAS  Google Scholar 

  18. Maheswari PU, Palaniandavar M (2004) DNA binding and cleavage activity of [Ru(NH3)4(diimine)]Cl2 Complexes. Inorg Chim Acta 357:901

    Article  CAS  Google Scholar 

  19. Yang XJ, Drepper F, WU B, Sun WH, Haehnel W, Janiak C (2005) From model compounds to protein binding: synthesis, characterizations and fluorescences studies of [RuII(bipy)(terpy)L]2+ complexes (bipy = 2,2’ – bipyridine; terpy = 2,2’: 6’,2” – terpyridine; L = imiddazole, pyrazole and derivatives, cytochrome c). Dalton Trans 21(2):256–267

    Article  Google Scholar 

  20. Sava G, Pacer S, Berganmo A, Cocchettio M, Mestroni G, Allesio E (1995) Effects of ruthenium complexes on experimental tumors: irrelevance of cytotoxicity for metastasis inhibition. Chem Biol Interact 95:109–126

    Article  PubMed  CAS  Google Scholar 

  21. Beckford FA, Shaloski M Jr., Leblanc G, Thessbng J, Lesley C (2009) Microwave synthesis of mixed ligand diimine–thiosemicarbazone complexes of ruthenium (II): biophysical reactivity and Cytotoxicity. Dalton Trans 48:10757–10764

    Google Scholar 

  22. Morris RE, Aird RE, Murdoch PD, Chen HM, Cummings J, Hughes ND, Parsons S, Parkin A, Boyd G, Jodrell DI, Sadler PJ (2001) Inhibition of Cancer Cell Growth by Ruthenium(II) Arene Complexes. J Med Chem 44:3616–3621

    Article  PubMed  CAS  Google Scholar 

  23. Friedman AE, Chambron JC, Sauvage JP, Turro NJ, Barton JK (1990) Molecular “Light Switch” for DNA Ru(bpy)2(dppz) 2+. J Am Chem Soc 112:4960

    Article  CAS  Google Scholar 

  24. Hartshorn RM, Barton JK (1992) Novel Dipyridophenazine Complexes of Ruthenium (II): exploring Luminescent Reporters of DNA. J Am Chem Soc 114:5919

    Article  CAS  Google Scholar 

  25. Praveen Kumar Yata M, Shilpa P, Nagababu MR, Reddy LR, Kotha NM, Gabra SS (2012) Study of DNA Light Switch Ru(II) Complexes: synthesis, Characterization, Photocleavage and Antimicrobial Activity. J Fluoresc 22:835–847

    Article  PubMed  Google Scholar 

  26. Shobha Devi C, Yata Praveen Kumar P, Nagababu MS, Reddy R, Gabra NM, Satyanarayana S (2012) DNA binding characteristics of Ru(II) Complexes and their “light switch” on off effect in presence of Co(II) and EDTA. J Iran Chem Soc 9:671–680

    Article  CAS  Google Scholar 

  27. Shobha Devi C, Satyanarayana S (2012) Synthesis, characterization and DNA - binding properties of Ru(II) molecular “light switch” complexes. J Coord Chem 65:474–486

    Article  Google Scholar 

  28. Shilpa M, Penubaka Nagababu J, Naveen Lavanya Latha A, Gaytri Devi A, Nagarjuna YP, Kumar SS (2011) DNA-interactions of ruthenium(II) & Cobalt(III) phenanthroline and bipyridyl complexes with a planar aromatic ligand 2-(2 fluoronyl) 1H-imidazo [4,5-f][1,10-Phenanthroline]. J Incl Phenom Macrocycl Chem 70:187–195

    Article  CAS  Google Scholar 

  29. Ashwini Kumar K, Reddy KL, Satyanarayana S (2010) Study of the interaction between ruthenium (II) complexes and CT-DNA, Synthesis, Characterization, Photocleavage and Antimicrobial activity studies. Supramol Chem 22:629–643

    Article  Google Scholar 

  30. Vidhisha S, Reddy KL, Ashwini Kumar K, Satyanarayana S (2010) Synthesis, DNA interactions of ruthenium (II) complexes with polypyridyl ligand: 2-(2, 5-dimethoxyphenyl)-1H-imidazo [4, 5-f][1, 10]-phenanthroline. Transit Met Chem 35:1027–1034

    Article  CAS  Google Scholar 

  31. Ashwini Kumar K, Reddy KL, Satyanarayana S (2010) Synthesis, DNA interaction and Photocleavage studies of ruthenium(II) complexes with 2- (pyrrole) imidazo [4,5-f] [1,10-phenanthroline as an intercalative ligand. Transit Met Chem 35:713–720

    Article  Google Scholar 

  32. Reddy KL, Harish Y, Reddy K, Satyanarayana S (2009) DNA- binding and Photocleavage properties of Ru(ΙΙ) polypyridyl complexes with DNA and their toxicity studies on eukaryotic microorganisms. Nucleosides Nucleotides Nucleic Acids 28:953–968

    Article  PubMed  CAS  Google Scholar 

  33. Ashwini Kumar K, Reddy KL, Satyanarayana S (2010) Synthesis, characterization and DNA binding studies of ruthenium(II) complexes with 2-benzo[b] furan-2-yl-1H-imidazo [4,5-f] [1,10] phenanthroline as an intercalative ligand. J Coord Chem 63:3676–3687

    Article  Google Scholar 

  34. Nagababu P, Shilpa M, Ira Bhatnagar PBN, Sreenivas Y, Kumar P, Reddy KL, Satyanarayana S (2010) Synthesis, Characterization, DNA Binding Properties, Fluorescence Studies and Toxic activity of cobalt(III) and ruthenium(II) polypyridyl complexes. J Fluoresc 21(2):563–572

    Article  PubMed  Google Scholar 

  35. Shilpa M, Nagababu P, Kumar YP, Naveena J, Latha L, Rajender Reddy M, Satyanaraayana S (2011) DNA-interactions of ruthenium(II) complexes with planar aromatic ligands. J Fluoresc 21:1155–1164

    Article  PubMed  CAS  Google Scholar 

  36. Liu XW, Li J, Li H, Zheng KC, Chao H, Ji LN (2005) Synthesis, characterization, DNA-binding and photocleavage of complexesRu(phen)2 (6-OH-dppz)]2+ and [Ru(phen)2 (6-NO2 -dppz)] 2+. J Inorg Biochem 99:2372–2380

    Article  PubMed  CAS  Google Scholar 

  37. Liu YJ, Wei XY, Mei WJ, He LX (2007) Synthesis, characterization and DNA binding studies of ruthenium (II) complexes: [Ru(bpy)2(dtmi)]2+ and [Ru(bpy)2(dtni)]2+. Trans Met Chem 32:762–768

    Article  CAS  Google Scholar 

  38. Tan LF, Chao H (2007) DNA-binding and photocleavage studies of mixed polypyridyl ruthenium (II) complexes with calf thymus DNA. Inorg Chim Acta 360:2016–2022

    Article  CAS  Google Scholar 

  39. Liu JG, Ye BH, Li H, Zhen QX, Ji LN (1999) Polypyridyl ruthenium(II) complexes containing intramolecular hydrogen-bond ligand: syntheses, characterization and DNA-binding properties. J Inorg Biochem 76:265–271

    Article  CAS  Google Scholar 

  40. Perrin D, Annarego WLF, Perrin DR (1980) Purification of laboratory chemicals, 2nd edn. Pergamon Press, New York

    Google Scholar 

  41. Marmur J (1961) A procedure for the isolation of deoxyribonucleic acid from micro-organisms. J Mol Biol 3:208–218

    Article  CAS  Google Scholar 

  42. Reichmann ME, Rice SA, Thomas CA, Doty P (1954) Crystalline Δ4-Androsten-17β-o1-3, 16-dione. J Am Chem Soc 76:3047–3053

    Article  CAS  Google Scholar 

  43. Yamada M, Tanaka Y, Yoshimoto Y, Kuroda Shimao S (1992) Synthesis and properties of diamino-substituted dipyrido [3, 2-a: 20, 30-c] phenazine. J Bull Chem Soc Jpn 65:1006–1011

    Article  CAS  Google Scholar 

  44. Sullivan BP, Salmon DJ, Meyer T (1978) Mixed Phosphine 2, 2′- Bipyridine Complexes of Ruthenium. Inorg Chem 17:3334–3341

    Article  CAS  Google Scholar 

  45. Wolfe A, Shimer GH, Meehan T (1987) Polycyclic aromatic hydrocarbons physically intercalate into duplex regions of denatured DNA. Biochemistry 26:6392–6396

    Article  PubMed  CAS  Google Scholar 

  46. Mc Ghee JD, Von Hippel PH (1974) Theoretical aspects of DNAprotein interactions: co-operative and non-co-operative binding of large ligands to a one-dimensional homogeneous lattice. J Mol Biol 86:469–489

    Article  CAS  Google Scholar 

  47. Chaires JB, Dattagupta N, Crothers DM (1982) Self association of daunomycin. Biochemistry 21:3927–3932

    Article  PubMed  CAS  Google Scholar 

  48. Satyanarayana S, Dabrowiak JC, Chaires JB (1993) Tris (phenanthroline) ruthenium (II) enantiomer interactions with DNA: mode and specificity of binding. Biochemistry 32:2573–2584

    Article  PubMed  CAS  Google Scholar 

  49. Tselepi-Kalouli E, Katsaros N (1989) The Interaction of [Ru(NH3)5Cl]2+ and [Ru(NH3)6]3+ ions with DNA. J Inorg Biochem 37:271–282

    Article  PubMed  CAS  Google Scholar 

  50. Steck EA, Day AR (1943) Reactions of Phenanthraquinone and Retenequinone with Aldehydes and Ammonium Acetate in Acetic Acid Solution. J Am Chem Soc 65:452

    Article  CAS  Google Scholar 

  51. Tan L, Shen J, Liu J, Jin LZL, Weng C (2012) Spectral characteristics, DNA-binding and cytotoxicity of two functional Ru(II) mixed-ligand complexes. Dalton Trans 41:4575

    Article  PubMed  CAS  Google Scholar 

  52. Zhou XH, Ye BH, Li H, Liu JG, Xiang Y, Ji LN (1999) Mono and bi-nuclear ruthenium(II) containing a new asymmetric ligand 3-(pyrazin-2-yl)-as-triazino[5,6-f]1,10-phenanthroline: synthesis, Characterization and DNA-binding properties. J Chem Soc Dalton Trans 9:1423

    Article  Google Scholar 

  53. Nair RB, Teng ES, Kirkland SL, Murphy CJ (1998) Synthesis and DNA-binding properties of [Ru (NH3)4dppz] 2+. Inorg Chem 37:139–141

    Article  PubMed  CAS  Google Scholar 

  54. Moucheron C, Mesmaeker AKD, Choua C (1997) Photophysics of Ru(phen)2(PHEHAT)2+: a Novel “Light Switch” for DNA and Photo-oxidant for Mononucleotides. Inorg Chem 36:584–592

    Article  CAS  Google Scholar 

  55. Gao F, Chao H, Zhou F, Yuan YX, Peng B, Ji LN (2006) DNA interactions of a functionalized ruthenium(II) mixed-polypyridyl complex [Ru(bpy)2ppd]2+. Inorg Biochem 100:1487–1494

    Article  CAS  Google Scholar 

  56. Joseph R, Lakowicz GW (1973) Quenching of fluorescence by oxygen. Probe for structural fluctuations in macromolecules. Biochemistry 12:4161–4170

    Article  Google Scholar 

  57. Lakowicz JR (1983) Principles of fluorescence spectroscopy. Plenum Press, New York

    Book  Google Scholar 

  58. Drew WL, Barry AL, ’Toole RO, Sherris JC (1972) Clinical Microbiology and Immunology Reliability of the Kirby-Bauer Disc Diffusion Method for Detecting Methicillin-Resistant Strains of Staphylococcus aureus. Appl Environ Microbiol 24:240

    Google Scholar 

  59. Satyanarayana S, Dabrowiak JC, Chaires JB (1992) Neither delta- nor lambda- tris- (phenanthroline) ruthenium (II) binds to DNA by classical intercalation. Biochemistry 31:9319

    Article  PubMed  CAS  Google Scholar 

  60. Ashwini Kumar K, Kotha Laxma Reddy S, Vidhisha SS (2009) Synthesis, Characterization and DNA binding and Photocleavage studies of [Ru(bpy)2BDPPZ]2+, [Ru(dmb)2BDPPZ]2+ and [Ru(phen)2BDPPZ]2+ complexes and their antimicrobial activity. Appl Organomet Chem 23:409–420

    Article  Google Scholar 

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Acknowledgments

We are grateful to DST PURSE project F.No A-30 for financial support and also CFRD & DBT- OU ISLARE Osmania University Hyderabad for helping the analysis and cytotoxic studies.

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Srishailam, A., Kumar, Y.P., Gabra, N.M.D. et al. Synthesis, DNA-binding, Cytotoxicity, Photo Cleavage, Antimicrobial and Docking Studies of Ru(II) Polypyridyl Complexes. J Fluoresc 23, 897–908 (2013). https://doi.org/10.1007/s10895-013-1209-7

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  • DOI: https://doi.org/10.1007/s10895-013-1209-7

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