Four new monomeric pyrophosphate complexes, namely [Co(phen)(2)(H(2)P(2)O(7))] x 4 H(2)O (1 x 4 H(2)O), [Ni(phen)(2)(H(2)P(2)O(7))] x 8 H(2)O (2 x 8 H(2)O), [Cu(phen)(H(2)O)(H(2)P(2)O(7))] (3) and {[Cu(phen)(H(2)O)(P(2)O(7))][Na(2)(H(2)O)(8)]} x 6 H(2)O (4 x 14 H(2)O) have been isolated and structurally characterized. The impact of pH and stoichiometry in obtaining 1-4 is described. These complexes have been tested against the adriamycin-resistant ovarian cancer cell line A2780/AD, revealing highly significant (nM) IC(50) values, compared to microM IC(50) values for cisplatin controls.

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The minimal inhibitory concentrations (MICs) of copper and cobalt based dimeric pyrophosphate complexes with capping 1,10-phenanthroline groups on clinical isolates of C. albicans (28 isolates), C. krusei (20 isolates) and C. tropicalis (20 isolates) are reported. C. albicans was inhibited by the cobalt complex better than by the copper complex, while C. krusei demonstrated the opposite results. C. tropicalis showed similar sensitivities to both metals in terms of calculated MIC50 values but was more sensitive to cobalt when MIC90 values were noted. Knockout strains of C. albicans that had the copper efflux protein P-type ATPase (CRP1), the copper binding metallothionein CUP1 or both CRP1/CUP1 removed clearly demonstrate that the origins of copper resistant in C. albicans lies primarily in the P-type ATPase, with the MT playing an important secondary role in the absence of the efflux protein. This study suggests that certain strains of Candida have evolved to protect against particular metal ions and that in the case of C. albicans, a primary invasive fungal species, cobalt may be a good starting-point for new therapeutic development.

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