The aqueous speciation, formation constants, and solution structure were determined for a new insulin-mimetic organic vanadium(V) compound (ammonium (dipicolinato)oxovanadate(V)). The solution properties of the system were characterized by using potentiometry, 1H, 13C, and 51V NMR 1D and 2D spectroscopy, and UV/visible spectroscopy. These studies were conducted using the crystalline compound as well as combinations of the free ligand and the metal salt. The major complex is most stable in the acidic pH range, although it does protonate at low pH. It protonates at pH ∼1 and decomposes below pH 0. The dipic ligand is coordinated in a tridentate manner throughout the pH range studied. Protonation at low pH takes place on one of the oxo groups. Dynamic processes were explored using 1H and 13C EXSY NMR spectroscopy. VO2dipic- was found to exchange between the complex and the ligand at high and at low pH values. In the intermediate-pH range, no evidence for exchange processes was obtained, documenting the inertness of the complex at pH 3−4. The high stability and inertness in the pH 3−4 region may be of biological significance since the combination of high stability and low lability suggests the complex will be more resistant to hydrolysis at the pH of the stomach.

A representative set of vanadium(IV and V) compounds in varying coordination environments has been tested in the concentration range 1 to 10(-6) mM, using transformed mice fibroblasts (cell line SV 3T3), with respect to their short-term cell toxicity (up to 36 hours) and their ability to stimulate glucose uptake by cells. These insulin-mimetic tests have also been carried out with non-transformed human fibroblasts (cell line F26). The compounds under investigation comprise established insulin-mimetic species such as vanadate ([H(2)VO(4)](-)), [VO(acetylacetonate)(2)], [VO(2)(dipicolinate)](-) and [VO(maltolate)(2)], and new systems and coordination compounds containing OO, ON, OS, NS and ONS donor atom sets. A vitality test assay, measuring the reduction equivalents released in the mitochondrial respiratory chain by intracellular glucose degradation, is introduced and the results are counter-checked with (3)H-labelled glucose. Most compounds are toxic at the 1 mM concentration level, and most compounds are essentially non-toxic and about as effective as or more potent than insulin at concentrations of 0.01 mM and below. V(V) compounds tend to be less toxic than V(IV)compounds, and complexes containing thio functional ligands are somewhat more toxic than others. Generally, ON ligation is superior in insulin-mimetic efficacy to OO or O/ NS coordination, irrespective of the vanadium oxidation state. There is, however, no striking correlation between the nature of the ligand systems and the insulin-mimetic potency in these cell culture tests, encompassing 41 vanadium compounds, the results on 22 of which are reported in detail here. The syntheses and characteristics of various new compounds are provided together with selected speciation results. The crystal and molecular structures of [[VO(naph-tris)](2)] [where naph-tris is the Schiff base formed between o-hydroxynaphthaldehyde and tris(hydroxymethyl)amine] are reported. Electronic supplementary material to this paper can be obtained by using the Springer Link server located at http://dx.doi.org/10.1007/s00775-001-0311-5.

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The interactions of Cu II , Zn II and Fe II with Triapine (3-aminopyridine-2-carbaldehyde thiosemicarbazone), which is currently undergoing phase II clinical trials as a chemotherapeutic antitumour agent, were investigated in a water/DMSO mixture. The proton-dissociation constants of the ligands, the stability constants and the coordination modes of the metal complexes formed were determined by pH-potentiometric, UV/Vis spectrophotometric, EPR, 1 H NMR spectroscopic and ESI-MS methods. Two N-terminally dimethylated derivatives of Triapine were also studied. Mono-and bis-ligand com-[a]