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Synthesis and X-ray crystal structure of [Ag(phendio)2]ClO4 (phendio = 1,10-phenanthroline-5,6-dione) and its effects on fungal and mammalian cells

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Abstract

The Cu(II) and Ag(I) complexes, [Cu(phendio)3](ClO4)2⋅4H2O and [Ag(phendio)2]ClO4 (phendio = 1,10-phenanthroline-5,6-dione), are prepared in good yield by reacting phendio with the appropriate metal perchlorate salt. The X-ray crystal structure of the Ag(I) complex shows it to have a pseudo tetrahedral structure. `Metal-free' phendio and the Cu(II) and Ag(I) phendio complexes strongly inhibit the growth of the fungal pathogen Candida albicans, and are more active than their 1,10-phenanthroline analogues. The simple Ag(I) salts, AgCH3CO2, AgNO3 and AgClO4.H2O display superior anti-fungal properties compared to analogous simple Cu(II) and Mn(II) salts, suggesting that the nature of the metal ion strongly influences activity. Exposing C. albicans to `metal-free' phendio, simple Ag(I) salts and [Ag(phendio)2]ClO4 causes extensive, non-specific DNA cleavage. `Metal-free' phendio and [Ag(phendio)2]ClO4 induce gross distortions in fungal cell morphology and there is evidence for disruption of cell division. Both drugs also exhibit high anti-cancer activity when tested against cultured mammalian cells.

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References

  • Berners-Price SJ, Johnson RK, Giovenella AJ, Faucette LF, Mira-belli CK, Sadler PJ. 1988 Antimicrobial and anticancer activ-ity of tetrahedral, chelated, diphosphine silver(I) complexes: comparison with copper and gold. J Inorg Biochem 33, 285–295.

    Google Scholar 

  • Bult A, Bajema BL, Klasen HB, Meeting HJ, Fox Jr. CL. 1981 Re-marks on the structure-activity relationship of some antibacterial silver non-sulfanilamide compounds. Pharm Weekblad Sci Edn 3, 79–81.

    Google Scholar 

  • Butler HM, Hurse A, Thursky E, Shulman A. 1969 Bactericidal ac-tion of selected phenanthroline chelates and related compounds. Australian J Expt Biol and Med Sci 47, 541–52.

    Google Scholar 

  • Calderazzo F, Marchetti F, Pampaloni G, Passarelli V. 1999 Co-ordination properties of 1,10-phenanthroline-5,6-dione towards group 4 and 5 metals in low and high oxidation states. J Chem Soc Dalton Trans 4389–4396.

  • Coyle B, Kavanagh K, McCann M, Devereux M, Geraghty M. 2003a Mode of anti-fungal activity of 1,10-phenanthroline and its Cu(II), Mn(II) and Ag(I) complexes. BioMetals 16, 321–329.

    Google Scholar 

  • Coyle B, Kinsella P, McCann M, et al. 2003b Induction of apoptosis in yeast and mammalian cells by exposure to 1,10 phenanthroline metal complexes. Submitted for publication.

  • Dwyer FP, Reid IK, Shulman A, Laycock GM, Dixon S. 1969 The biological actions of 1,10-phenanthroline and 2,2-bipyridine hy-drochlorides, quaternary salts and metal chelates and related compounds. 1. Bacteriostatic action on selected gram-positive, gram-negative and acid-fast bacteria. Australian J Expt Biol and Med Sci 47, 203–218.

    Google Scholar 

  • Eckert TS, Bruice TC, Gaynor JA, Weinreb SM. 1982 Some electro-chemical and chemical properties of methoxatin and analogous quinoquinones. Biochemistry 79, 2533–2536.

    Google Scholar 

  • Eckert TS, Bruice TC. 1983 Chemical properties of phenan-throlinequinones and the mechanism of amine oxidation by o-quinones of medium redox potentials. J Am Chem Soc 105, 4431–4441.

    Google Scholar 

  • Fox GA, Bhattacharya S, Pierpoint CG. 1991 Structural and elec-trochemical properties of binuclear complexes containing 1,10-phenanthroline-5,6-diolate as a bridging ligand. Inorg Chem 30, 2895–2899.

    Google Scholar 

  • Geraghty M, Cronin F, Devereux M, McCann M. 2000 Synthesis and antimicrobial activity of copper(II) and manganese(II)á, ù-dicarboxylate complexes. BioMetals 13, 1–8.

    Google Scholar 

  • Girgis AY, Sohn YS, Balch AL. 1975 Preparation and oxidation of some quinone adducts of transition metal complexes. Inorg Chem 14, 2327–2321.

    Google Scholar 

  • Goss CA and Abruña HD. 1985 Crystal structures, electronic absorption and reflectance spectral, electrochemical and elec-trocatalytic properties of 1,10-phenanthroline-5,6-dione com-plexes of transition metals. Inorg Chem 24, 4263–4267.

    Google Scholar 

  • Hilt G, Farbawi T, Heineman WR, Steckhan E. 1997 An analytical study of the redox behaviour of 1,10-phenanthroline-5,6-dione, its transition-metal complexes, and its N-monomethylated de-rivative with regard to their efficiency as mediators of NAD(P)+ regeneration. Chem Eur J 3, 79–88.

    Google Scholar 

  • Igdaloff D, Santi DV, Eckert TS, Bruice TC. 1983Effects of 1,7-and 1,10-phenanthroline dione on tissue culture cells. Biochemical Pharmacology 32, 172–174.

    Google Scholar 

  • Kontoyiannis DP and Lewis RE. 2002 Antifungal drug resistance in pathogenic fungi. Lancet 359, 1135–1143.

    Google Scholar 

  • Lei Y, Shi C, Anson FC. 1996 Effects of coordination to transition metals on the hydration and electroactivity of the chelating ligand 1,10-phenanthroline-5,6-dione. Inorg Chem 35, 3044–3049.

    Google Scholar 

  • Liu H, Du M, Ling X-B, Bu X-H, Zhang R-H. 2000 Syn-thesis and crystal structure of the copper(II) complex with tris-( 1,10-phenanthroline-5,6-dione). Chinese J Struct Chem (Jiegou Huaxue) 19, 427–431.

    Google Scholar 

  • Lunel FM, Meis FG, Voss A. 1999 Nosocomial fungal infections: Candidemia. Diag Micro and Infect Dis 34, 213–220.

    Google Scholar 

  • MacLeod, RA. 1952 The toxicity of o-phenanthroline for lactic acid bacteria.J BiolChe m 197, 751–761.

    Google Scholar 

  • Martin A and Clynes M. 1993 Comparison of 5 microtitre colormet-ric assays for in vitro cytotoxicity testing and cell proliferation assays. Cytotechnology 11, 49–58.

    Google Scholar 

  • McCann M, Geraghty M, Devereux M, O'Shea D, Mason J, O'Sullivan L. 2000 Insights into the mode of action of the anti-Candida activity of 1,10-phenanthroline and its metal chelates. Metal-Based Drugs 7, 185–193.

    Google Scholar 

  • McCann M, Coyle B, Briody J. et al. 2003 Synthesis and antimicro-bial activity of (Z)-3-(1-imidazol-1-yl)-2-phenylpropenenitrile and its metal complexes: X-ray crystal structures of the Zn(II) and Ag(I) complexes. Polyhedron, in press.

  • Murtha DP. and Walton RA. 1973 Studies on coordination com-plexes of silver(II). VII. A comparative study of the X-ray photoelectron spectra of complexes of silver(II) and silver(I) containing nitrogen donor molecules. Silver 3d and nitrogen 1s binding energies. Inorg Chem 12, 368–372.

    Google Scholar 

  • Nordén B, Matsuoka Y, Kurucsev T. 1986 Nucleic acid-metal in-teractions: V. The effect of silver(I) on the structures of A-and B-DNA forms. Biopolymers 25, 1531–1545.

    Google Scholar 

  • Pallenberg AJ, Marschner TM, Barnhart DM. 1997 Phenanthroline complexes of the d 10 metals nickel(0), zinc(II) and silver(I)-comparison to copper(I) species. Polyhedron 16, 2711–2719.

    Google Scholar 

  • Paw W, Eisenberg R. 1997 Synthesis, characterization and spec-troscopy of dipyridocatecholate complexes of platinum. Inorg Chem 36, 2287–2293.

    Google Scholar 

  • Pfaller MA, Jones RN, Messer SA, Edmond MB, Wenzel RP. 1998 National surveillance of nosocomial blood stream infection due to Candida albicans: frequency of occurrence and anti-fungal susceptibility in the SCOPE programme. Diagnostic Microbial Infectious Disease 31, 327–332.

    Google Scholar 

  • Ratte HT. 1999 Bioaccumulation and toxicity of silver compounds: A review.Environmental Toxicology and Chemistry 18, 89–108 and references therein.

    Google Scholar 

  • Sheldrick GM. 2001 SHELXTL version 6.12, Bruker-AXS, Madison WI,.

    Google Scholar 

  • Smith GF and Cagle FW. 1947 The improved synthesis of 5-nitro-1,10-phenanthroline. J OrgChe m12, 781–784.

    Google Scholar 

  • Šponer J, Sabat M, Burda JV, Leszczynski J, Hobza P, Lippert B. 1999 Metal ion in non-complimentary DNA base pairs: an ab initio study of Cu(I), Ag(I) and Au(I) complexes with the cytosine-adenine base pair. JBIC 4, 537–545.

    Google Scholar 

  • Thurman RB and Gerba CP. 1989 The molecular mechanisms of copper and silver ion disinfection of bacteria and viruses. CRC Crit Rev Environ Control 18, 295–315, and references therein.

    Google Scholar 

  • Tilton RC and Rosenberg B. 1978 Reversal of the silver inhibition of microorganisms by agar. Appl Environ Microbiol 35, 1116–1120.

    Google Scholar 

  • Van den Bossche H, Dromer F, Improvissi I, Lozane-Chiu M, Rex JH, Sanglard D. 1998 Anti-fungal drug resistance in pathogenic fungi. Med Mycol 36, 119–128.

    Google Scholar 

  • Wells TNC, Scully P, Paravicini G, Proudfoot AEI, Payton MA. 1995 Mechanism of irreversible inactivation of phosphoman-nose isomerase by silver ions and flamazine. Biochemistry 34, 7896–7903.

    Google Scholar 

  • Wu J-Z, Li H, Zhang J-G, Xu J-H. 2002 Synthesis and DNA binding behavior of a dipyridocatecholate bridged dicopper(II) complex. Inorg Chem Commun 5, 71–75.

    Google Scholar 

  • Yamada M, Tanaka Y, Yoshimoto Y, Kurodo S, Shimao I. 1992 Synthesis and properties of diamino-substituted dipyrido[3,2-a:2,3-]phenazine. Bull Chem Soc Jpn 65, 1006–1011.

    Google Scholar 

  • Yamada Y, Sakurai H, Miyashita Y, Fujisawa K, Okamoto K-I. 2002 Crystal structures, electronic absorption and reflectance spectral behaviours, and electrochemical properties of five-coordinated chlorocopper(II) complexes with 5,6-disubstituted-1,10-phenanthroline. Polyhedron 21, 2143–2147.

    Google Scholar 

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Authors and Affiliations

  1. Chemistry Department and 2Biology Department, National University of Ireland Maynooth, Maynooth, Co. Kildare, Ireland

    Malachy McCann, Barry Coyle, Sinead McKay, Paul McCormack & Kevin Kavanagh

  2. Dublin Institute of Technology, Cathal Brugha Street, Dublin, Ireland

    Michael Devereux

  3. Chemistry Department, Loughborough University, Loughborough, Leics., LE11 3TU, UK

    Vickie McKee

  4. National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland

    Paula Kinsella, Robert O'Connor & Martin Clynes

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  1. Malachy McCann
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  2. Barry Coyle
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  4. Paul McCormack
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  8. Paula Kinsella
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McCann, M., Coyle, B., McKay, S. et al. Synthesis and X-ray crystal structure of [Ag(phendio)2]ClO4 (phendio = 1,10-phenanthroline-5,6-dione) and its effects on fungal and mammalian cells. Biometals 17, 635–645 (2004). https://doi.org/10.1007/s10534-004-1229-5

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