Synthesis and insulin-mimetic activities of metal complexes with 3-hydroxypyridine-2-carboxylic acid

Metal complexes of 3-hydroxypyridine-2-carboxylic acid (H2hpic), [Co(Hhpic)2(H2O)2] (1), [Fe(Hhpic)2(H2O)2] (2), [Zn(Hhpic)2(H2O)2] (3), [Mn(Hhpic)2(H2O)2] (4), and [Cu(Hhpic)2] (5) have been synthesized and characterized by mass spectrometry, elemental analysis, magnetic susceptibility, infrared, electronic absorption and electron paramagnetic resonance (EPR) spectroscopies. The solid-state structure of 1 has been established by X-ray crystallography. The EPR spectra of 4 and 5 displayed six and four-line hyperfine splitting patterns, respectively, due to coupling of the unpaired electron with the 55Mn (I = 5/2) nucleus and the 63Cu (I = 3/2) nucleus. In the EPR spectrum of 5, an additional five-line super-hyperfine splitting pattern was observed at 77 K, caused by additional interaction of the unpaired electron with ligand nitrogen atoms (I = 1), indicating that the structure of 5 was retained in dimethyl sulfoxide solution. The insulin-mimetic activity of these complexes was evaluated by means of in vitro measurements of the inhibition of free fatty acid (FFA) release from epinephrine-treated, isolated rat adipocytes. Complex 5 was found to exhibit the most potent insulin-mimetic activity among the complexes examined in this study.