New zinc(II) complexes with tetradentate amino acid derivatives: Structure characterization, solution chemistry, and in vitro insulinomimetic activity

Twelve new amino acid derivatives/Zn(II) complexes were prepared by the reactions of ZnSO₄ and nine tetradentate ligands, Gly, Ala, Val, Leu, Ser and His derivatives and three pentadentate ligands, Asp and His derivatives. The X-ray structure analysis of [Zn₃(N-pyridylmethyl-His)₃(H₂O)2] (ClO₄)₃·2H₂O revealed the formation of a trinuclear complex, in which three tetradentate ligands and two water molecules coordinate to three Zn(II), but the complex in an aqueous solution is present as a monomeric complex ion. Several Zn(II) complexes were found to have in vitro insulinomimetic activity which was estimated by the inhibition of free fatty acid release in isolated rat adipocytes treated with epinephrine. It was revealed that the insulinomimetic activities of Zn(II) complexes with the stability constants (log β) A less than 11 were higher than that of VOSO₄ and were comparable to that of ZnSO₄ as positive controls except in the cases of two complexes with Gly derivatives, Zn(N,N-dipyridylmethyl-Gly)⁺ and Zn(N,N'-trimethylene-bis-Gly).