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

The Cu(II) and Ag(I) complexes, [Cu(phendio)(3)](ClO4)(2).4H(2)O 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.