Cobalt(II) and cobalt(III) dipicolinate complexes: Solid state, solution, and in vivo insulin-like properties

The synthesis and characterization of Co(II) and Co(III) 2,6-pyridinedicarboxylate (dipic^2-) complexes are reported. Solid-state x-ray characterizations were performed on [Co(H₂dipic)(dipic)]·3H₂O and [Co(dipic)(μ-dipic)Co(H₂O)₅]· 2H₂O. Two coordination modes not previously observed in dipicolinate transition metal complexes were observed in these complexes; one involves metal coordination to the short C-O (C=O) bond, and the other involves metal coordination to a protonated oxygen atom. Solution studies, including paramagnetic NMR and UV-vis spectroscopy, were done showing the high stability and low lability of the Co(III) complex, whereas the Co(II) complexes exhibited ligand exchange in the presence of excess ligand. The [Co(dipic)₂]^2- complex has pH dependent lability and in this regard is most similar to the [VO₂dipic]^- complex. The [Co(dipic)₂]^2- was found to be effective in reducing the hyperlipidemia of diabetes using oral administration in drinking water in rats with STZ-induced diabetes. Oral administration of VOSO₄ was used as a positive control for metal efficacy against diabetes. In addition to providing a framework to evaluate structure-function relationships of various transition metal complexes in alleviating the symptoms of diabetes, this work describes novel aspects of structural and solution cobalt chemistry.