Cobalt(II) and Cobalt(III) Dipicolinate Complexes:  Solid State, Solution, and in Vivo Insulin-like Properties

Abstract

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(H(2)dipic)(dipic)].3H(2)O and [Co(dipic)(mu-dipic)Co(H(2)O)(5)].2H(2)O. 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 [VO(2)dipic](-) 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 VOSO(4) 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.

Interaction of pyridine-2,5-dicarboxylic acid with heavy metal ions in aqueous solutions

“…This information documents that in neutral and alkaline solutions the ligand exists as dianionic pdca 2− . Given the recent results showing that some transition metal complexes with the 2,6-dipicolinic acid have beneficial effects in normalizing elevated blood glucose levels in STZ-induced diabetic rats [15,16], fundamental information on the solution chemistry of metal complexes with dipicolinic acid isomers is important. The present study was carried out to investigate equilibria in solutions of H 2 pdca in the presence of the divalent metal ions Zn(II), Ni(II), Pb(II), Cd(II), and Cu(II) over a wide pH range.…”

Interaction of pyridine‐ and 4‐hydroxypyridine‐2,6‐dicarboxylic acids with heavy metal ions in aqueous solutions

“…In addition, at higher pH the ionization of the OH-group of 4-hydroxypyridine-2,6-dicarboxylic acid occurs, pK a3 value being 10.9 [22]. Given the recent results showing that some transition metal complexes with the pyridine-2,6-dicarboxylic acid have beneficial effects in normalizing elevated blood glucose levels in diabetic rats [40,41], fundamental information on solution chemistry of metal complexes with pyridinedicarboxylic acid ligands is important. The present study was carried out to specify equilibria in solutions of pyridine-2,6-dicarboxylic and 4-hydroxypyridine-2,6-dicarboxylic acids in the presence of the divalent metal ions Cu(II), Pb(II), and Cd(II) in a wide pH range, and to compare the results with that obtained earlier for the isomer of the pyridine-2,6-dicarboxylic acid, i.e., the pyridine-2,5-dicarboxylic acid [42].…”

Synthesis and characterization of complexes of a novel proton transfer salt and their inhibition studies on carbonic anhydrase isoenzymes

“…Continuing the path to synthesize proton transfer compounds, our group has focused on forming ion pairs between H 2 DPC and various organic bases, such as 2-aminobenzothiazole 2 , 2-amino-6-methylbenzothiazole 3 , 2-amino-6-methoxybenzothiazole 4 , 2-amino-4-methylpyridine 5 , 2-hydroxyethylpiperazine 6 . The interest of metal complexes for H 2 DPC and its deprotonated forms, HDPC À and DPC 2À , stems from their interesting structural features with various coordination modes 1 , stabilization of unusual oxidation states 7 and insulin-mimetic effects 8,9 . Benzothiazoles and their simple metal complexes are well known for their biological activities, such as antitumor agents, antimicrobial, antifungal, analgesics, anti-inflammatory, anti HIV, carbonic anhydrase inhibition and local anesthestic 2-4, [10][11][12][13][14][15] .…”