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    Progressing the Synthesis, Coordination Chemistry and Biological Evaluation of Phenanthrolines

    McCarron, Pauraic (2014) Progressing the Synthesis, Coordination Chemistry and Biological Evaluation of Phenanthrolines. PhD thesis, National University of Ireland Maynooth.

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    The work described in this thesis concerns: (i) the synthesis and characterisation of ternary 1,10-phenenthroline/dicarboxylate Ag(I), Cu(II) and Mn(II) complexes and their in vitro/in vivo antifungal, antibacterial and antineoplastic capabilities; (ii) the development of a novel, high yielding, rapid and chromatography-free synthetic protocol for the formation of families of existing and new imidazo-phenanthroline ligands that allow for the modular assembly and covalent inclusion of an ensemble of varied functional groups and cellular targeting molecules; (iii) the synthesis of Cu(II) complexes incorporating these imidazo-phenanthroline ligands and their assessment as artificial mellonucleases; (iv) the synthesis of phenanthroline-oxazine (phenoxazine) ligands via an unusual cyclisation reaction with 1,10-phenanthroline-5,6-dione and specific aromatic amino acid esters; (v) the synthesis of a novel imidazo-pheanthroline-folic acid-appended ligand and its corresponding metal complexes with the view to selectively target folate receptor expressing cancer cells and activated macrophages. A selection of complexes were screened, in vitro, for growth inhibition activity against a range of fungal and bacterial pathogens and were found to have broad spectrum activity. The most active complexes were then tested, in vivo, for cytotoxicity and antifungal activity using the Galleria mellonella insect model. Healthy G. mellonella larvae appeared to be unaffected by the complexes at concentrations up to 500 μg/cm3. The most active complex, [Mn2(ƞ1ƞ1μ2-oda)(phen)4(H2O)2][Mn2(ƞ1ƞ1μ2-oda)(phen)4(ƞ1-oda)2].4H2O (13), increased the survival rate of larvae administered with a lethal dose of C. albicans and was much more efficacious than the clinically used antifungal drug, ketoconazole. Against two different Mycobacterium tuberculosis strains, the Mn(II) complexes exhibited potent antimycobacterial activity, with 13 being 3-fold more active than the prescription drug, isoniazid. This Mn(II) complex was also highly cytotoxic towards other bacterial cells. The Cu(II) bis-imidazo-phenanthroline complexes proved to be effective nuclease mimetic agents. In particular, a heteronuclear, ferrocene-appended imidazo-phenanthroline Cu(II) complex, displayed potent DNA scission activity and retained this activity in the presence of a large excess of the powerful metal ion sequestrant, EDTA. Cu(II)-based complexes were generally the most effective anticancer agents (in vitro), and [Cu2(oda)(phen)4](ClO4)2.2.76H2O.EtOH (14) was particularly cytotoxic towards the cancerous A549 alveolar cell line.

    Item Type: Thesis (PhD)
    Keywords: Progressing; Synthesis; Coordination Chemistry; Biological Evaluation; Phenanthrolines;
    Academic Unit: Faculty of Science and Engineering > Chemistry
    Item ID: 9124
    Depositing User: IR eTheses
    Date Deposited: 05 Jan 2018 15:49
      Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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