Synthesis, Characterization, and Low-Toxicity Study of a Magnesium(II) Complex Containing an Isovanillate Group

Abstract

The beneficial effect of polyphenols and magnesium­(II) against oxidative stress motivated our research group to explore the antioxidant activity of phenMgIso, an aqueous soluble magnesium­(II) complex containing 1,10-phenanthroline (phen) and isovanillic acid (Iso) as ligands. Combined electrospray ionization–mass spectrometry and DOSY-NMR techniques identified two complexes in methanolic solution: hexacoordinated [Mg­(phen)2(Iso)]+ and tetracoordinated [Mg­(phen)­(Iso)]+. The cyclic voltammogram of phenMgIso in the anodic region showed a cyclic process that interrupts the isovanillic acid degradation, probably by stabilization of the corresponding phenoxyl radical via complexation with Mg­(II), which is interesting for antioxidant applications. phenMgIso competes with 2,2,6,6-tetramethylpiperidine by 1O2 with IC50(1O2) = 15 μg m–1 and with nitrotetrazolium blue chloride by superoxide ions (IC50(O2 •–) = 3.6 μg mL–1). Exposure of both zebrafish (2 mg L–1) and wistar male rats (3 mg kg–1 day–1 dose for 21 days) to phenMgIso does not cause mortality or visual changes compared with the respective control groups, thus phenMgIso could be considered safe under the conditions of this study. Moreover, no significant changes in comparison to both control groups were observed in the biochemical parameters on the brain-acetylcholinesterase activity, digestive tract enzyme catalase, and glutathione-S-transferase. Conversely, the performance of superoxide dismutase activity in wistar male rats increased in the presence of a complex, resulting in enhanced capacity of rats for superoxide radical enzymatic scavenging. The synergistic action of phenMgIso may be explained by the strong electrostatic interaction between Mg­(II) and the O,O­(phenolate) group, which makes the Iso ligand easier to oxidize and deprotonate, generating a cyclic stable species under oxidative conditions.

Effect of a Magnesium(II) Complex Containing Isovanillate Group on Lipid Oxidation of Porcine Muscles

“…The Mg–Iso complex is easy to synthesize, water-soluble, nontoxic and was designed to potentiate synergistic action between Mg­(II) and the phenolate group from the isovanillic acid ligand. In aqueous solution, Figure , a tetra- and a hexa-coordinated form of the Mg–Iso complex are in equilibrium as was demonstrated by MS-ESI . Recent studies in our laboratory have demonstrated in vitro antioxidant activity properties of the Mg–Iso complex both against singlet oxygen and superoxide radical with IC 50 = 15 μg mL –1 and IC 50 = 3.7 μg mL –1 , respectively.…”

“…This difference may be explained by coordination of the isovanillate ion to {Mg­(phen)} 2+ moiety. Magnesium­(II) causes an increment in the acidity of the coordinated isovanillate by delocating the charge toward {Mg­(phen)} 2+ making the hydroxyl group present at the isovanallate more polarized as predicted by the Mulliken charge distribution …”

“…The Mg–Iso complex was synthesized as previously described by refluxing equimolar amounts of isovanilic acid, 1,10-phenathroline, triethylamine, and Mg­(CH 3 COO) 2 ·4H 2 O in methanol. A characterization of the complex was previously published …”

“…Recent studies in our laboratory have demonstrated in vitro antioxidant activity properties of the Mg–Iso complex both against singlet oxygen and superoxide radical with IC 50 = 15 μg mL –1 and IC 50 = 3.7 μg mL –1 , respectively. Also, in vivo a protective action was demonstrated by the increase in activity of the enzyme superoxide dismutase in the presence of Mg–Iso, resulting in an enhancement of the radical enzymatic scavenging capacity of superoxide for Zebra fish and Wister male rats …”

Heterodinuclear Mg(II)M(II) (M=Cr, Mn, Fe, Co, Ni, Cu and Zn) Complexes for the Ring Opening Copolymerization of Carbon Dioxide/Epoxide and Anhydride/Epoxide

“…First row transition metal ions are selected because the current best heterodinuclear catalysts, that is, Mg(II)Co(II) and Mg(II)Zn(II), both feature a transition metal [18f,g,19] . The Mg(II) partner is selected due to its track record for high rates in carbon dioxide/epoxide ROCOP catalysis and for its abundance, light weight, low cost, lack of colour and low toxicity [22] …”