Silver ciprofloxacin (CIPAG): a successful combination of chemically modified antibiotic in inorganic–organic hybrid

  • I. Milionis
  • C. N. Banti
  • I. Sainis
  • C. P. Raptopoulou
  • V. Psycharis
  • N. Kourkoumelis
  • S. K. Hadjikakou
Original Paper


The new silver(I) ionic, water soluble, compound {[Ag(CIPH)2]NO3∙0.75MeOH∙1.2H2O} (CIPAG) was obtained by reacting silver(I) nitrate with the antibiotic ciprofloxacin (CIPH). The complex was characterized by m.p., mid-FT-IR, 1H-NMR, UV–Vis spectroscopic techniques. The crystal structures of both CIPAG and the hexahydrated neutral free drug {[CIPH]∙6(H2O)} (2) were characterized by X-ray crystallography. Two neutral ligands are datively bonded to the metal ion through the piperidinic nitrogen atoms forming a cationic {[Ag(CIPH)2]+} counter part which is neutralized by a nitrate group. The antibacterial effect of CIPAG and the commercially available hydrochloric salt of the antibiotic ({[CIPH 2 + ]∙Cl } (3)) were tested against the bacterial species Pseudomonas aeruginosa (PAO1), Staphylococcus epidermidis (St. epidermidis) and Staphylococcus aureus (St. aureus) by the mean of minimum inhibitory concentration, minimum bactericidal concentration and their inhibitory zone (IZ). The influence of CIPAG and 3 against the formation of biofilm of PAO1 or St. aureus was also evaluated by mean of biofilm elimination concentration. The IZ caused by CIPAG which has been loaded in poly-hydroxyethylmethacrylate, is determined. The genotoxicity of CIPAG and 3 is tested in vitro against normal human corneal epithelial cells (HCET cells), by the presence of micronucleus in HCET cells and in vivo by mean of Allium cepa test.


Biological inorganic chemistry Silver(I) compounds Ciprofloxacin Pseudomonas aeruginosa Staphylococcus epidermidis Staphylococcus aureus 



Neutral hexahydrated 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic acid


Protonated chloride ionic salt of 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic acid


Biofilm elimination concentration


1-Cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic acid




Ethylene glycol dimethacrylate


Normal human corneal epithelial cells


Hydroxyethyl methacrylate


Inhibitory zone


Minimum bactericidal concentration


Molecular dynamics


Mitotic Index


Minimum inhibitory concentration




Mycobacterium tuberculosis


Pseudomonas aeruginosa



SRB assay

Sulforhodamine B assay

St. aureus

Staphylococcus aureus

St. epidermidis

Staphylococcus epidermidis



(1) This work was carried out in partial fulfillment of the requirements for an M.Sc. thesis of I.M. within the graduate program in Medicinal Chemistry under the supervision of SKH. (2) CNB and SKH would like to thank the Unit of Bioactivity Testing of Xenobiotics, of the University of Ioannina, for providing access to the facilities. (3) CNB and SKH would like to thank the Atherothrombosis Research Centre of the University of Ioannina for providing access to the fluorescence microscope. (4) The COST Action CA15114 “Anti-Microbial Coating Innovations to prevent infectious diseases (AMICI)” is acknowledged for the stimulating discussions. (5) Ciprofloxacin hydrochloric salt was purchased from Help Pharmaceutical which is acknowledged. HCET cells were kindly provided by Dr Maria Notara (Research Fellow, Dept. of Ophthalmology, University Hospital of Cologne, Germany) who is acknowledge. (6) The synthesis of CIPAG is protected by Greek patent No. 108941. The authors of this paper are included to the patent’s inventors.

Supplementary material

775_2018_1561_MOESM1_ESM.pdf (1.8 mb)
Supplementary material 1 (PDF 1817 kb)


  1. 1.
    Tabbara KF, El-Sheikh HF, Aabed B (2001) Extended wear contact lens related bacterial keratitis. Br J Ophthalmol 85:842–847CrossRefGoogle Scholar
  2. 2.
    Stapleton F, Carnt N (2012) Contact lens-related microbial keratitis: how have epidemiology and genetics helped us with pathogenesis and prophylaxis. Eye 26:185–193CrossRefPubMedGoogle Scholar
  3. 3.
    Schaefer F, Bruttin O, Zografos L, Guex-Crosier Y (2000) Bacterial keratitis: a prospective clinical and microbiological study. Br J Ophthalmol 84:327–328CrossRefGoogle Scholar
  4. 4.
    Appelbaum PC, Hunter PA (2000) The fluoroquinolone antibacterials: past, present and future perspectives. Int J Antimicrob Agents 16:5–15CrossRefPubMedGoogle Scholar
  5. 5.
    Reidy JJ, Hobden JA, Hill JM, Forman K, O’Callaghan RJ (1991) The efficacy of topical ciprofloxacin and norfloxacin in the treatment of experimental Pseudomonas keratitis. Cornea 10:25–28CrossRefPubMedGoogle Scholar
  6. 6.
    Islan GA, Mukherjee A, Castro R (2015) Development of biopolymer nanocomposite for silver nanoparticles and ciprofloxacin controlled release. Int J Biol Macromol 72:740–750CrossRefPubMedGoogle Scholar
  7. 7.
    Silver S (2003) Bacterial silver resistance: molecular biology and uses and misuses of silver compounds. FEMS Microbiol Rev 27:341–353CrossRefPubMedGoogle Scholar
  8. 8.
    Kyros L, Banti CN, Kourkoumelis N, Kubicki M, Sainis I, Hadjikakou SK (2014) Synthesis, characterization, and binding properties towards CT-DNA and lipoxygenase of mixed-ligand silver(I) complexes with 2-mercaptothiazole and its derivatives and triphenylphosphine. J Biol Inorg Chem 19:449–464CrossRefPubMedGoogle Scholar
  9. 9.
    Sainis I, Banti CN, Owczarzak AM, Kyros L, Kourkoumelis N, Kubicki M, Hadjikakou SK (2016) New antibacterial, non-genotoxic materials, derived from the functionalization of the anti-thyroid drug methimazole with silver ions. J Inorg Biochem 160:114–124CrossRefPubMedGoogle Scholar
  10. 10.
    Turel I, Bukovec P, Quiros M (1997) Crystal structure of ciprofloxacin hexahydrate and its characterization. Int J Pharm 152:59CrossRefGoogle Scholar
  11. 11.
    Fabbiani FPA, Dittrich B (2008) Redetermination and invariom refinement of 1-cyclo-propyl-6-fluoro-4-oxo-7-(piperazin-4-ium-1-yl)-1,4-dihydroquinoline-3-carboxylate hexahydrate at 120 K. Acta Crystallogr Sect E: Struct Rep Online 64:o2354CrossRefGoogle Scholar
  12. 12.
    Fabbiani FPA, Arlin J-B, Buth G, Dittrich B, Florence AJ, Herbst-Irmer R, Sowa H (2011) Intermolecular interactions, disorder and twinning in ciprofloxacin–2,2-difluoroethanol (2/3) and ciprofloxacin–water (3/14.5). Acta Crystallogr Sect C Cryst Struct Commun 67:120Google Scholar
  13. 13.
    Vitorino GP, Sperandeo NR, Caira MR, Mazzieri MR (1050) A supramolecular assembly formed by hetero association of ciprofloxacin and norfloxacin in the solid state: co-crystal synthesis and characterization. Cryst Growth Des 2013:13Google Scholar
  14. 14.
    Li X, Hu Y, Gao Y, Zhang GGZ, Henry RF (2006) A methanol hemisolvate of ciprofloxacin. Acta Crystallogr Sect E: Struct Rep Online 62:o5803CrossRefGoogle Scholar
  15. 15.
    Fabbiani FPA, Dittrich B, Florence AJ, Gelbrich T, Hursthouse MB, Kuhs WF, Shankland N, Sowa H (2009) Crystal structures with a challenge: high-pressure crystallisation of ciprofloxacin sodium salts and their recovery to ambient pressure. Cryst Eng Comm 11:1396CrossRefGoogle Scholar
  16. 16.
    Mahapatra S, Venugopala KN, Row TNG (1866) A device to crystallize organic solids: structure of ciprofloxacin, midazolam, and ofloxacin as targets. Cryst Growth Des 2010:10Google Scholar
  17. 17.
    Batsanov SS (2001) Van der Waals radii of elements, 2001, 37, 871–885. Inorg Mater 37:871–885 (translated from Neorganicheskie Materialy, Vol. 37, No. 9, 2001, pp. 1031–1046) CrossRefGoogle Scholar
  18. 18.
    Anacona JR, Toledo C (2001) Synthesis and antibacterial activity of metal complexes of ciprofloxacin. Transit Metal Chem 26:228–231CrossRefGoogle Scholar
  19. 19.
    Psomas G (2008) Mononuclear metal complexes with ciprofloxacin: synthesis, characterization and DNA-binding properties. J Inorg Biochem 102:1798–1811CrossRefPubMedGoogle Scholar
  20. 20.
    Parshikov IA, Freeman JP, Lay JO Jr, Beger RD, Williams AJ, Sutherland JB (1999) Regioselective transformation of ciprofloxacin to N-acetylciprofloxacin by the fungus Mucor ramannianus. FEMS Microbiol Lett 177:131–135CrossRefPubMedGoogle Scholar
  21. 21.
    Wiegand I, Hilpert K, Hancock REW (2008) Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc 3:163–175CrossRefPubMedGoogle Scholar
  22. 22.
    Danguy Cavassin E, Francisco L, de Figueiredo P, Pinhata Otoch J, Martins Seckler M, Angelo de Oliveira R, Fantinelli Franco F, Spolon Marangoni V, Zucolotto V, Sara Shafferman Levin A, Figueiredo Costa S (2015) Comparison of methods to detect the in vitro activity of silver nanoparticles (AgNP) against multidrug resistant bacteria. J Nanobiotechnol 13:64–80Google Scholar
  23. 23.
    Shungu DL, Weinberg E, Gadebusch HH (1983) Tentative interpretive standards for disk diffusion susceptibility testing with norfloxacin (MK-0366, AM-715). Antimicrob Agents Chemother 23:256–260CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Pereira MP, Kelley SO (2011) Maximizing the therapeutic window of an antimicrobial drug by imparting mitochondrial sequestration in human cells. J Am Chem Soc 133:3260–3263CrossRefPubMedGoogle Scholar
  25. 25.
    Savić ND, Milivojevic DR, Glišić BĐ, Ilic-Tomic T, Veselinovic J, Pavic A, Vasiljevic B, Nikodinovic-Runic J, Djurana MI (2016) A comparative antimicrobial and toxicological study of gold(III) and silver(I) complexes with aromatic nitrogen-containing heterocycles: synergistic activity and improved selectivity index of Au(III)/Ag(I) complexes mixture. RSC Adv 6:13193–13206CrossRefGoogle Scholar
  26. 26.
    Cellini L, Di Campli E, Masulli M, Di Bartolomeo S, Allocati N (1996) Inhibition of Helicobacter pylori by garlic extract (Allium sativum). FEMS Immunol Med Microbiol 13:273–277CrossRefPubMedGoogle Scholar
  27. 27.
    Kostenko V, Ceri H, Martinuzzi RJ (2007) Increased tolerance of Staphylococcus aureus to vancomycin in viscous media. FEMS Immunol Med Microbiol 51:277–288CrossRefPubMedGoogle Scholar
  28. 28.
    Ude Z, Romero-Canelón I, Twamley B, Fitzgerald Hughes D, Sadler PJ, Marmion CJ (2016) A novel dual-functioning ruthenium(II)–arene complex of an anti-microbial ciprofloxacin derivative-Anti-proliferative and anti-microbial activity. J Inorg Biochem 160:210–217CrossRefPubMedGoogle Scholar
  29. 29.
    Motyl M, Dorso K, Barrett J, Giacobbe R (2005) Basic microbiological techniques used in antibacterial drug discovery. In: Current protocols in pharmacology unit 13A.3.1–13A.3.22. Wiley, New YorkGoogle Scholar
  30. 30.
    Kalinowska-Lis U, Szewczyk EM, Checinska L, Wojciechowski JM, Wolf WM, Ochocki J (2014) Synthesis, characterization, and antimicrobial activity of silver(I) and copper(II) complexes of phosphate derivatives of pyridine and benzimidazole. Chem Med Chem 9:169–176CrossRefPubMedGoogle Scholar
  31. 31.
    Pal S, Yoon EJ, Park SH, Choi EC, Song JM (2010) Metallopharmaceuticals based on silver(I) and silver (II) polydiguanide complexes: activity against burn wound pathogens. J Antimicrob Chemother 65:2134–2140CrossRefPubMedGoogle Scholar
  32. 32.
    Matuschek E, Brown DFJ, Kahlmeter G (2014) Development of the EUCAST disk diffusion antimicrobial susceptibility testing method and its implementation in routine microbiology laboratories. Clin Microbiol Infect 20:o255–o266CrossRefPubMedGoogle Scholar
  33. 33.
    Lee J-H, Park J-H, Seob Cho H, Woo Joo S, Hwan Cho M, Lee J (2013) Anti-biofilm activities of quercetin and tannic acid against Staphylococcus aureus. Biofouling 29:491–499CrossRefPubMedGoogle Scholar
  34. 34.
    Nishimura S, Tsurumoto T, Yonekura A, Adachi K, Shindo H (2006) Antimicrobial susceptibility of Staphylococcus aureus and Staphylococcus epidermidis biofilms isolated from infected total hip arthroplasty cases. J Orthop Sci 11:46–50CrossRefPubMedGoogle Scholar
  35. 35.
    Viganor L, Galdino ACM, Nunes APF, Santos KRN, Branquinha MH, Devereux M, Kellett A, McCann M, Santos ALS (2016) Anti-Pseudomonas aeruginosa activity of 1,10-phenanthroline-based drugs against both planktonic- and biofilm-growing cells. J Antimicrob Chemother 71:128–134CrossRefPubMedGoogle Scholar
  36. 36.
    Stepanovic S, Vukovic D, Dakic I, Savic B, Svabic-Vlahovic M (2000) A modified microtiter-plate test for quantification of staphylococcal biofilm formation. J Microbiol Methods 40:175–179CrossRefPubMedGoogle Scholar
  37. 37.
    Preston CAK, Khoury AE, Reid G, Bruce AW, Costertone JW (1996) Pseudomonas aeruginosa biofilms are more susceptible to ciprofloxacin than to tobramycin. Int J Antimicrob Agents 7:251–256CrossRefPubMedGoogle Scholar
  38. 38.
    González-Sánchez MI, Perni S, Tommasi G, Glyn Morris N, Hawkins K, López-Cabarcos E, Prokopovich P (2015) Silver nanoparticle based antibacterial methacrylate hydrogels potential for bone graft applications. Mater Sci Eng C Mater Biol Appl 50:332–340CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Cook AD, Sagers RD, Pitt WG (1993) Bacterial adhesion to poly(HEMA)-based hydrogels. J Biomed Mater Res 27:119–126CrossRefPubMedGoogle Scholar
  40. 40.
    Dutta D, Kumar N, Willcox MDP (2016) Antimicrobial activity of four cationic peptides immobilised to poly-hydroxyethylmethacrylate. Biofouling 32:429–438CrossRefPubMedGoogle Scholar
  41. 41.
    Andrade-Vivero P, Fernandez-Gabriel E, Alvarez-Lorenzo C, Concheiro A (2007) Improving the loading and release of NSAIDs from pHEMA hydrogels by copolymerization with functionalized monomers. J Pharm Sci 96:802–813CrossRefPubMedGoogle Scholar
  42. 42.
    Tsai T-H, Chen W-L, Hu F-R (2010) Comparison of fluoroquinolones: cytotoxicity on human corneal epithelial cells. Eye 24:909–917CrossRefPubMedGoogle Scholar
  43. 43.
    Torres-Bugarín O, Guadalupe Zavala-Cerna M, Nava A, Flores-García A, Luisa Ramos-Ibarra M (2014) Potential uses, limitations, and basic procedures of micronuclei and nuclear abnormalities in buccal cells. Dis Markers, Article ID 956835Google Scholar
  44. 44.
    Banti CN, Papatriantafyllopoulou C, Manoli M, Tasiopoulos AJ, Hadjikakou SK (2016) Nimesulide silver metallodrugs, containing the mitochondriotropic, triaryl derivatives of pnictogen; anticancer activity against human breast cancer cells. Inorg Chem 55:8681–8696CrossRefPubMedGoogle Scholar
  45. 45.
    Li Y, Chen DH, Yan J, Chen Y, Mittelstaedt RA, Zhang Y, Biris AS, Heflich RH, Chen T (2012) Genotoxicity of silver nanoparticles evaluated using the Ames test and in vitro micronucleus assay. Mutat Res 745:4–10CrossRefPubMedGoogle Scholar
  46. 46.
    Celik A, Ogenler O, Comelekoglu U (2005) The evaluation of micronucleus frequency by acridine orange fluorescent staining in peripheral blood of rats treated with lead acetate. Mutagenesis 20:411–415CrossRefPubMedGoogle Scholar
  47. 47.
    Sahu SC, Roy S, Zheng J, Yourick JJ, Sprando RL (2014) Comparative genotoxicity of nanosilver in human liver HepG2 and colon Caco2 cells evaluated by fluorescent microscopy of cytochalasin B-blocked micronucleus formation. J Appl Toxicol 34:1200–1208CrossRefPubMedGoogle Scholar
  48. 48.
    Fernandes TCC, Mazzeo DEC, Marin-Morales MA (2007) Mechanism of micronuclei formation in polyploidizated cells of Allium cepa exposed to trifluralin herbicide. Pestic Biochem Physiol 88:252–259CrossRefGoogle Scholar
  49. 49.
    Leme DM, Marin-Morales MA (2009) Allium cepa test in environmental monitoring: a review on its application. Mutat Res 682:71–81 (and references there in) Google Scholar
  50. 50.
    Urgut OS, Ozturk II, Banti CN, Kourkoumelis N, Manoli M, Tasiopoulos AJ, Hadjikakou SK (2016) Antimony(III) halide complexes with dithiocarbamate ligands derived from thiuram degradation: the effect of the molecule’s close contacts on in vitro cytotoxic activity. Mater Sci Eng C Mater Biol Appl 58:396–408CrossRefPubMedGoogle Scholar
  51. 51.
    Giacomello G, Malatesta P, Quaglia G (1964) Action of thalidomide on radical meristems of Allium cepa. Nature 201:940–941CrossRefPubMedGoogle Scholar
  52. 52.
    Yıldız M, Hakkı Cigerci I, Konuk M, Fidan AF, Terzi H (2009) Determination of genotoxic effects of copper sulphate and cobalt chloride in Allium cepa root cells by chromosome aberration and comet assays. Chemosphere 75:934–938CrossRefPubMedGoogle Scholar
  53. 53.
    Ahmad Z, Minkowski A, Peloquin CA, Williams KN, Mdluli KE, Grosset JH, Nuermberger EL (2011) Activity of the fluoroquinolone DC-159a in the initial and continuation phases of treatment of murine tuberculosis. Antimicrob Agents Chemother 55:1781–1783CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Pucci MJ, Ackerman M, Thanassi JA, Shoen CM, Cynamon MH (2010) In vitro antituberculosis activities of ACH-702, a novel isothiazoloquinolone, against quinolone-susceptible and quinolone-resistant isolates. Antimicrob Agents Chemother 54:3478–3480CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Molina-Torres CA, Barba-Marines A, Valles-Guerra O, Ocampo-Candiani J, Cavazos-Rocha N, Pucci MJ, Castro-Garza J, Vera-Cabrera L (2014) Intracellular activity of tedizolid phosphate and ACH-702 versus Mycobacterium tuberculosis infected macrophages. Ann Clin Microbiol Antimicrob 13:13CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Drlica K, Franco RJ (1988) Inhibitors of DNA topoisomerases. Biochemistry 27:2253–2259CrossRefPubMedGoogle Scholar
  57. 57.
    Blower TR, Williamson BH, Kerns RJ, Berger JM (2016) Crystal structure and stability of gyrase–fluoroquinolone cleaved complexes from Mycobacterium tuberculosis. Proc Natl Acad Sci USA 113:1706–1713CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Aubry A, Pan X-S, Fisher LM, Jarlier V, Cambau E (2004) Mycobacterium tuberculosis DNA gyrase: interaction with quinolones and correlation with antimycobacterial drug activity. Antimicrob Agents Chemother 48:1281–1288CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Matrat S, Aubry A, Mayer C, Jarlier V, Cambau E (2008) Mutagenesis in the alpha3alpha4 GyrA helix and in the Toprim domain of GyrB refines the contribution of Mycobacterium tuberculosis DNA gyrase to intrinsic resistance to quinolones. Antimicrob Agents Chemother 52:2909–2914CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Skauge T, Turel I, Sletten E (2002) Interaction between ciprofloxacin and DNA mediated by Mg2+-ions. Inorg Chim Acta 339:239–247CrossRefGoogle Scholar
  61. 61.
    CrystalClear (2005) Rigaku/MSC Inc., The Woodlands, TexasGoogle Scholar
  62. 62.
    Sheldrick GM (2008) A short history of SHELX. Acta Crystallogr A64:112–122CrossRefGoogle Scholar
  63. 63.
    Sheldrick GM (2015) Crystal structure refinement with SHELXL. Acta Crystallogr C71:3–8Google Scholar
  64. 64.
    Pruzanski W, Saito S (1988) Comparative study of phagocytosis and intracellular bactericidal activity of human monocytes and polymorphonuclear cells. Application of fluorochrome and extracellular quenching technique. Inflammation 12:87–97CrossRefPubMedGoogle Scholar
  65. 65.
    Miliotis MD (1991) Acridine orange stain for determining intracellular enteropathogens in HeLa cells. J Clin Microbiol 29:830–831PubMedPubMedCentralGoogle Scholar
  66. 66.
    Matsushima T, Hayashi M, Matsuoka A, Jr M, Ishidate KF, Miura Y, Shimizu Y, Suzuki K, Morimoto H, Ogura K, Koshi K, Sofuni T (1999) Validation study of the in vitro micronucleus test in a Chinese hamster lung cell line (CHL/IU). Mutagenesis 14:569–580CrossRefPubMedGoogle Scholar
  67. 67.
    Fenech M, Chang WP, Kirsch-Volders M, Holland N, Bonassi S, Zeiger E (2003) HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutat Res 534:65–75CrossRefPubMedGoogle Scholar
  68. 68.
    Muller K, Kasper P, Muller L (1993) An assessment of the in vitro hepatocyte micronucleus assay. Mutat Res 292:213–224CrossRefPubMedGoogle Scholar
  69. 69.
    Kovalchuk I, Kovalchuk O, Arkhipov A, Hohn B (1998) Transgenic plants are sensitive bioindicators of nuclear pollution caused by the Chernobyl accident. Nat Biotechnol 16:1054–1059CrossRefPubMedGoogle Scholar
  70. 70.
    Thomsen R, Christensen MH (2006) MolDock: a new technique for high-accuracy molecular docking. J Med Chem 49:3315–3321CrossRefPubMedGoogle Scholar
  71. 71.
    Krieger E, Vriend G (2015) New ways to boost molecular dynamics simulations. J Comput Chem 36:996–1007CrossRefPubMedGoogle Scholar
  72. 72.
    Hornak V, Abel R, Okur A, Strockbine B, Roitberg A, Simmerling C (2006) Comparison of multiple amber force fields and development of improved protein backbone parameters. Proteins 65:712–725CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Krieger E, Nielsen JE, Spronk CAEM, Vriend G (2006) Fast empirical pKa prediction by Ewald summation. J Mol Graph Model 25:481–486CrossRefPubMedGoogle Scholar

Copyright information

© SBIC 2018

Authors and Affiliations

  • I. Milionis
    • 1
  • C. N. Banti
    • 1
  • I. Sainis
    • 2
  • C. P. Raptopoulou
    • 3
  • V. Psycharis
    • 3
  • N. Kourkoumelis
    • 4
  • S. K. Hadjikakou
    • 1
  1. 1.Section of Inorganic and Analytical Chemistry, Department of ChemistryUniversity of IoanninaIoanninaGreece
  2. 2.Cancer Biobank CenterUniversity of IoanninaIoanninaGreece
  3. 3.Institute of Nanoscience and Nanotechnology, NCSR “Demokritos”AttikisGreece
  4. 4.Medical Physics Laboratory, Medical SchoolUniversity of IoanninaIoanninaGreece

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