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Synthesis, Spectral Properties and DFT Calculations of new Ruthenium (II) Polypyridyl Complexes; DNA Binding Affinity and in Vitro Cytotoxicity Activity

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Abstract

In this paper a novel ligand debip (2–(4–N,N–diethylbenzenamine)1H–imidazo[4,5–f] [1, 10]phenanthroline) and its Ru(II) polypyridyl complexes [Ru(L)2(debip)]2+, (L = phen (1), bpy (2) and dmb (3)) have been synthesized and characterized by spectroscopic techniques. The DNA binding studies for all these complexes were examined by absorption, emission, quenching studies, viscosity measurements and cyclic voltammetry. The light switching properties of complexes 1–3 have been evaluated. Molecular docking, Density Functional Theory (DFT) and time dependent DFT calculations were performed. The Ru(II) complexes exhibited efficient photocleavage activity against pBR322 DNA upon irradiation and exhibited good antimicrobial activity. Also investigated 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay, lactate dehydrogenase (LDH) release assay and reactive oxygen species (ROS) against selected cancer cell lines (HeLa, PC3, Lancap, MCF-7 and MD-MBA 231).

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References

  1. Blanpain C (2013) Tracing the cellular origin of cancer. Nat Cell Biol 15:126–134

    Article  CAS  PubMed  Google Scholar 

  2. Galanski M, Jakupec MA, Keppler BK (2005) Update of the preclinical situation of anticancer platinum complexes: novel design strategies and innovative analytical approaches. Curr Med Chem 12:2075–2094

    Article  CAS  PubMed  Google Scholar 

  3. Li W, Han BJ, Yao JH, Jiang GB, Liu YJ (2015) Cytotoxicity in vitro, cell migration and apoptotic mechanism studies induced by ruthenium(II) complexes. RSC Adv 5:24534–24543

    Article  CAS  Google Scholar 

  4. Zhang CX, Lippard SJ (2003) New metal complexes as potential therapeutics. Curr Opin Chem Biol 7:481–489

    Article  CAS  PubMed  Google Scholar 

  5. Ronconi L, Sadler PJ (2007) Insights into the Acid–Base properties of PtIV–Diazidodiam(m)inedihyroxido complexes from multinuclear NMR spectroscopy. Coord Chem Rev 251:1633–1648

    Article  CAS  Google Scholar 

  6. Han BJ, Jiang GB, Wang J (2015) Ruthenium(II) polypyridyl complexes: synthesis, cytotoxicity in vitro, reactive oxygen species, mitochondrial membrane potential and cell cycle arrest studies. Transit Met Chem 40:153–160

    Article  CAS  Google Scholar 

  7. El-ajaily MM, Abdullah HA, Al-janga A, Saad EE, and Maihub AA (2015) Zr(IV), la(III), and Ce(IV) chelates with 2-[(4-[(Z)-1-(2-Hydroxyphenyl)ethylidene]aminobutyl)- ethanimidoyl]phenol: synthesis, Spectroscopic Characterization, and Antimicrobial Studies Advances in Chemistry 15

  8. Niyazi H, Hall JP, O'Sullivan K, Winter G, Sorensen T, Kelly JM, Cardin CJ (2012) Crystalstructures of lambda-[Ru(phen)(2)dppz](2+) with oligonucleotides containing TA/TA and AT/ATsteps show two intercalation modes. Nat Chem 4:621–628

    Article  CAS  PubMed  Google Scholar 

  9. Nonat AM, Quinn SJ, Gunnlaugsson T (2009) Mixed f-d coordination complexes as dual visible- and near-infrared-emitting probes for targeting DNA. Inorg Chem 48:4646–4648

    Article  CAS  PubMed  Google Scholar 

  10. Ryan J, Quinn S, Gunnlaugsson T (2008) Highly effective DNA Photocleavage by novel "rigid" Ru(bpy)3-4-nitro- and −4-amino-1,8-naphthalimide conjugates. Inorg Chem 47:401–403

    Article  CAS  PubMed  Google Scholar 

  11. Zeglis BM, Pierre VC, Barton JK (2007) Metallo-intercalators and metallo-insertors. Chem Commun (Camb) pp 4565–4579

  12. Moucheron C, De Mesmaeker AK, Kelly JM (1997) Photoreactions of ruthenium(II) and osmium(II) complexes with deoxyribonucleic acid (DNA). J Photochem Photobiol B 40:91–106

    Article  CAS  PubMed  Google Scholar 

  13. Erkkila KE, Odom DT, Barton JK (1999) Recognition and reaction of metallointercalators with DNA. Chem Rev 99:2777–2795

    Article  CAS  PubMed  Google Scholar 

  14. Song H, Kaiser JT, Barton JK (2012) Crystal structure of Delta-[Ru(bpy)(2)dppz](2+) bound to mismatched DNA reveals side-by-side metalloinsertion and intercalation. Nat Chem 4:615–620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gill MR, Thomas JA (2012) Ruthenium(II) polypyridyl complexes and DNA-from structural probes to cellular imaging and therapeutics. Chem Soc Rev 41:3179–3192

    Article  CAS  PubMed  Google Scholar 

  16. Zheng KC, Wang JP, Peng WL, Liu XW, Yun FC (2001) Studies on 6,6′- disubstitution effects of the dpq in [Ru(bpy)2(dpq)]2+ with DFT method. J Phys Chem A 105:10899–10905

    Article  CAS  Google Scholar 

  17. Zheng KC, Liu XW, Wang JP, Yun FC, Ji LN (2003) DFT studies on the molecular orbitals and related properties of [Ru(phen)2(9,9′ -2R- dpq)]2+(R=NH2,OH,H and F). J Mol Struct (THEOCHEM) 637:195–203

    Article  CAS  Google Scholar 

  18. Mei WJ, Liu J, Zheng KC, Lin LJ, Chao H et al (2003) Experimental and theoretical study on DNA-binding and photocleavage properties of chiral complexes - and -[Ru(bpy)2L] (L o-hpip, m-hpip and p- hpip). Dalton Trans 7:1352–1359

    Article  Google Scholar 

  19. Hotze ACG, Bacac M, Velders AH, Jansen BAJ, Kooijman H, Spek AL, Haasnoot JG, Reedij KJ (2003) New cytotoxic and water-soluble bis(2-phenylazopyridine)ruthenium(II) complexes. J Med Chem 46:1743–1750

    Article  CAS  PubMed  Google Scholar 

  20. Elmes RB, Orange KN, Cloonan SM, Williams DC, Gunnlaugsson T (2011) Luminescent ruthenium(II) polypyridyl functionalized gold nanoparticles; their DNA binding abilities and application as cellular imaging agents. J Am Chem Soc 133:15862–15865

    Article  CAS  PubMed  Google Scholar 

  21. Elmes RB, Erby M, Bright SA, Williams DC, Gunnlaugsson T (2012) Photophysical and biological investigation of novel luminescent Ru(II)-polypyridyl-1,8-naphthalimide Troger's bases as cellular imaging agents. Chem Commun (Camb) 48:2588–2590

    Article  CAS  Google Scholar 

  22. Venkat RP, Rjender RM, Srishailam A, Praveen KY, Nagamani C, Deepika N, Nagasuryaprasad K, Satyanarayana singh SS, Satyanarayana S (2015) Design, synthesis, DNA-binding affinity, cytotoxicity, apoptosis, and cell cycle arrest of Ru(II) polypyridyl complexes. Anal Biochem Methods Biol Sci 485:49–58

    Article  Google Scholar 

  23. Rjender RM, Venkat RP, Praveen KY, Srishailam A, Nambigari N, Satyanarayana S (2014) Synthesis, characterization, DNA binding, light switch "on and off", docking studies and cytotoxicity, of ruthenium(II) and cobalt(III) polypyridyl complexes. J Fluoresc 24:803–817

    Article  Google Scholar 

  24. Shobha DC, Anil KD, Singh SS, Gabra NM, Deepika N, Yata PK, Satyanarayana S (2013) Synthesis, interaction with DNA, cytotoxicity, cell cycle arrest and apoptotic inducing properties of ruthenium(II) molecular "light switch" complexes. Eur J Med Chem 64:410–421

    Article  Google Scholar 

  25. Srishailam A, Yata PK, Gabra NM, Reddy PV, Deepika N, Veerababu N, Satyanarayana S (2013) Synthesis, DNA-binding, cytotoxicity, photo cleavage, antimicrobial and docking studies of Ru(II) polypyridyl complexes. J Fluoresc 23:897–908

    Article  CAS  PubMed  Google Scholar 

  26. Yamada M, Tanaka Y, Yoshimoto Y, Kuroda S, Shimao I (1992) Synthesis and properties of diamino substistuted di pyrido [3,4-a:2′,3′-c] phenazine. Bull Chem Soc Jpn 65:2007–2009

    Article  CAS  Google Scholar 

  27. Schatzschneider U, Niesel J, Ott I, Gust R, Alborzinia H, Wolf S (2008) Cellular uptake, cytotoxicity, and metabolic profiling of human cancer cells treated with ruthenium(II) polypyridyl complexes [Ru(bpy)2(N--N)]Cl2 with N--N=bpy, phen, dpq, dppz, and dppn. Chem Med Chem 3:1104–1109

    Article  CAS  PubMed  Google Scholar 

  28. Tan CP, Liu J, Chen LM, Shi S, Ji LN (2008) Synthesis, structural characteristics, DNA binding properties and cytotoxicity studies of a series of Ru(III) complexes. J Inorg Biochem 102:1644–1653

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. 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  CAS  PubMed  Google Scholar 

  31. Barton JK, Danishefsky A, Raphael GJ (1984) Site-specific cleavage of left-handed DNA in pBR322 by A-co(DIP). J Am Chem Soc 106:2172–2176

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  33. Ghosh BK, Chakravorty A (1989) Electrochemical studies of ruthenium compounds part I. Ligand oxidation levels. Coord Chem Rev 95:239–294

    Article  CAS  Google Scholar 

  34. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, et al., (2009) Gaussian 09, Revision B.01. In Wallingford

  35. Becke AD (1993) Semiempirical hybrid functional with improved performance in an extensive chemical assessment. J Chem Phys 98:5648

    Article  CAS  Google Scholar 

  36. Becke AD (1996) Density-functional thermochemistry. IV A new dynamical correlation functional and implications for exact-exchange mixing. J Chem Phys 104:1040–1046

    Article  CAS  Google Scholar 

  37. Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37:785

    Article  CAS  Google Scholar 

  38. Hay PJ, Wadt WR (1985) Ab initio effective core potentials for molecular calculations. Potentials for the transition metal atoms Sc to hg. J Chem Phys 82:270

    Article  CAS  Google Scholar 

  39. Hay PJ, Wadt WR (1985) Ab initio effective core potentials for molecular calculations. Potentials for K to au including the outermost core orbitals. J Chem Phys 82:299

    Article  CAS  Google Scholar 

  40. Wadt WR, Hay PJ (1985) Ab initio effective core potentials for molecular calculations. Potentials for main group elements Na to bi. J Chem Phys 82:284

    Article  CAS  Google Scholar 

  41. Dennington R, Keith T, Milliam J (2009) Gauss view, version 5 Semichem Inc. Shawnee Mission, KS

  42. Miertuš S, Scrocco ET (1981) Electrostatic Interaction of a Solute with a Continuum. A Direct Utilization of AB Initio Molecular Potentials for the Prevision of Solvent Effects. J Chem Phys 55:117–129

    Google Scholar 

  43. Cossi M, Barone V, Cammi RT (1996) Ab initio study of solvated molecules: a new implementation of the polarizable continuum model. Chem Phys Lett 255:327–335

    Article  CAS  Google Scholar 

  44. Chitumalla RK, Gupta KSV, Malapaka C, Fallahpour Islam RA, Han L, Kotamarthi B, Singh SP (2014) Thiocyanate-free cyclometalated ruthenium(II) sensitizers for DSSC: a combined experimental and theoretical investigation. Phys Chem Chem Phys 16:2630

    Article  CAS  PubMed  Google Scholar 

  45. Diller DJ, Merz KM Jr (2001) High throughput docking for library design and library prioritization. Proteins 43:113–124

    Article  CAS  PubMed  Google Scholar 

  46. Gohlke H, Klebe G (2001) Statistical potentials and scoring functions applied to protein-ligand binding. Curr Opin Struct Biol 11:231–235

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  48. McGhee JD, Hippel VPH (1974) Theoretical aspects of DNA-protein 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  PubMed  Google Scholar 

  49. Gale PA (2011) Anion receptor chemistry. Chem Commun 47:82–86

    Article  CAS  Google Scholar 

  50. Jonathan AK, Elaine MB, Thorfinnur G (2012) Synthesis, structural characterisation and luminescent anion sensing studies of a Ru(II)polypyridyl complex featuring an aryl urea derivatised 2,2′-bpy auxiliary ligand. Inorg Chim Acta 381:236–242

    Article  Google Scholar 

  51. Hui C, Wen JM, Qi WH, Liang NJ (2004) Electronic effects on the interactions of complexes [Ru(phen)2(p-L)]2+ (L=MOPIP, HPIP, and NPIP) with DNA. Inorg Chim Acta 357:285–293

    Article  Google Scholar 

  52. Li G, Liu N, Liu S, Zhang S (2008) Electrochemical biosensor based on the interaction between copper(II) complex with 4,5-diazafluorene-9-one and bromine ligands and deoxyribonucleic acid. Electrochim Acta 53:2870–2876

    Article  CAS  Google Scholar 

  53. Drew WL, Barry AL, Toole RO, Sherris JC (1972) Reliability of the Kirby-Bauer disc diffusion method for detecting methicillin-resistant strains of Staphylococcus aureus. Appl Microbiol 24:240–247

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Barton JK, Raphael AL (1984) Photoactivated stereospecific cleavage of double-helical DNA by cobalt(III) complexes. J Am Chem Soc 106:2466–2468

    Article  CAS  Google Scholar 

  55. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  PubMed  Google Scholar 

  56. José CM, Moreno CJ, Puertollano E, Puertollano MA, de Pablo MA (2010) The antimicrobial peptide cecropin a induces caspase-independent cell death in human promyelocytic leukemia cells. Peptides 31:1494–1503

    Article  Google Scholar 

  57. Aronoff SL, MD, FACP, FACE, Berkowitz K, APRN, BC, FNP, CDE, Shreiner B, RN, MN, CDE, BC-ADM, Want L, RN, MS, CDE, CCRC, BC-ADM, Glucose Metabolism and Regulation: Beyond Insulin and Glucagon

  58. Hickman JA (1992) Apoptosis induced by anticancer drugs, Cancer. Metastasis Rev 11:121–139

    Article  CAS  Google Scholar 

  59. Darzynkiewicz Z (1990) Differential staining of DNA and RNA in intact cells and isolated cell nuclei with acridine orange. Methods Cel Biology 33:285–298

    Article  CAS  Google Scholar 

  60. Gorczyca W, Hotz MA, Lassota P, Traganos F (1992) Features of apoptotic cells measured by flow cytometry. Cytometry 13:795–808

    Article  PubMed  Google Scholar 

  61. Hawley ST, Hawley GR (2004) Flow cytometry protocols, 2nd edn. Humana Press, Totowa

    Book  Google Scholar 

  62. Shouval RS, Elazar Z (2007) ROS, mitochondria and the regulation of autophagy. Trends Cell Biol 17:422–427

    Article  Google Scholar 

  63. Adams DJ, Boskovic ZV, Theriault JR, Wang AJ, Stern AM, Wagner BK, Shamji AF, Schreiber SL (2013) Discovery of small-molecule enhancers of reactive oxygen species that are nontoxic or cause genotype-selective cell death. ACS Chem Biol 8:923–929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We are grateful to DBT New Delhi and UGC New Delhi for financial support, and CFRD, Osmania University, Hyderabad-07. The authors gratefully acknowledge Korea Research Fellowship program funded by the Ministry of Science, ICT and Future Planning through the National Research Foundation of Korea (2016H1D3A1936765) for performing the DFT studies.

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Authors and Affiliations

  1. Department of Chemistry, Osmania University, Hyderabad, Telangana State, 500007, India

    Rajender Reddy Mallepally, Nagamani Chintakuntla, Venkat Reddy Putta, Ravi Kumar Vuradi & Satyanarayana Sirasani

  2. Department of Biochemistry, Osmania University, Hyderabad, Telangana State, 500007, India

    Nagasuryaprasad K, Madhuri P & Satyanarayana Singh S

  3. Department of Nanoenergy Engineering, Pusan National University, Busan, 609-735, Republic of Korea

    Ramesh Kumar Chitumalla & Joonkyung Jang

  4. Inorganic & Physical Chemistry Division, CSIR−IICT, Tarnaka, Hyderabad, Telangana, 500007, India

    Nagababu Penumaka

  5. CSIR-NEERI Kolkata Zonal Laboratory, 1-8, Sector C, East Kolkata, Area Development Projecct, P.O. East Kolkata, Township, Kolkata, 700107, India

    Nagababu Penumaka

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  1. Rajender Reddy Mallepally
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Mallepally, R.R., Chintakuntla, N., Putta, V.R. et al. Synthesis, Spectral Properties and DFT Calculations of new Ruthenium (II) Polypyridyl Complexes; DNA Binding Affinity and in Vitro Cytotoxicity Activity. J Fluoresc 27, 1513–1530 (2017). https://doi.org/10.1007/s10895-017-2091-5

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