Ferromagnetic Coupling in "Double-Bridged" Dihydrogenpyrophosphate Complexes of Cobalt(II) and Nickel(II).

Three isostructural compounds of the formula {[M(bipy)(H2O)(H2P2O7)]2·2H2O} [bipy = 2,2'-bipyridine; M = Ni (1), Co (2), Mn (3)] have been isolated from aqueous solutions containing the corresponding metal(II) chloride hydrate with a bipy and sodium pyrophosphate solution in a 1:1:2 molar ratio, and their structures were determined by single-crystal X-ray diffraction. The structures of 1-3 consist of neutral aqua(2,2'-bipyridine)metal(II) dinuclear units bridged by two dihydrogenpyrophosphate groups adopting a bidentate/monodentate mode. Each metal ion in 1-3 is six-coordinate in a distorted octahedral geometry, with the reduced value of the angle subtended by the chelating bipy at the metal ion [79.6(1)° (1), 77.32(7)° (2), and 72.9(1)° (3)] being the main source of this distortion. The values of the intramolecular metal-metal separation are 5.271(1) Å (1), 5.3065(8) Å (2), and 5.371(1) Å (3). Magnetic susceptibility measurements on polycrystalline samples of 1-3 in the temperature range 1.9-300 K shows weak intramolecular ferromagnetic [J = +1.86(2) cm(-1) (1) and +0.25(1) cm(-1) (2)] and antiferromagnetic [J = -0.48(1) cm(-1) (3)] coupling, with the spin Hamiltonian being defined as H = -JSM1·SM1a. This rarely observed coordination mode for dihydrogenpyrophosphate leads to ferromagnetic coupling in complexes of nickel(II) or cobalt(II).

Clinical isolates of Candida albicans, Candida tropicalis, and Candida krusei have different susceptibilities to Co(II) and Cu(II) complexes of 1,10-phenanthroline.

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.

Expanding monomeric pyrophosphate complexes beyond platinum.

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.

Co(II) and Cu(II) pyrophosphate complexes have selectivity and potency against Mycobacteria including Mycobacterium tuberculosis.

Tuberculosis (TB) causes up to 10 million incident cases worldwide per annum. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains are leading factors in the resurgence of TB cases and the need to produce new agents to combat such infection. Herein, we describe Co(II) and Cu(II) metal based complexes that feature the pyrophosphate ligand with notable selectivity and marked potency against Mycobacterium tuberculosis, including MDR strains. Such complexes are confirmed to be bacteriocidal and not affected by efflux inhibitors. Finally, while susceptibility to copper has recently been established for M. tuberculosis, the greater efficacy of cobalt observed herein is of considerable note and in line with the discovery of a copper metallothionein in M. tuberculosis.