Complexes of Copper and Iron with Pyridoxamine, Ascorbic Acid, and a Model Amadori Compound: Exploring Pyridoxamine’s Secondary Antioxidant Activity

Abstract

The thermodynamic stability of 11 complexes of Cu(II) and 26 complexes of Fe(III) is studied, comprising the ligands pyridoxamine (PM), ascorbic acid (ASC), and a model Amadori compound (AMD). In addition, the secondary antioxidant activity of PM is analyzed when chelating both Cu(II) and Fe(III), relative to the rate constant of the first step of the Haber-Weiss cycle, in the presence of the superoxide radical anion (O2•−) or ascorbate (ASC−). Calculations are performed at the M05(SMD)/6-311+G(d,p) level of theory. The aqueous environment is modeled by making use of the SMD solvation method in all calculations. This level of theory accurately reproduces the experimental data available. When put in perspective with the stability of various complexes of aminoguanidine (AG) (which we have previously studied), the following stability trends can be found for the Cu(II) and Fe(III) complexes, respectively: ASC < AG < AMD < PM and AG < ASC < AMD < PM. The most stable complex of Cu(II) with PM (with two bidentate ligands) presents a ΔGf0 value of −35.8 kcal/mol, whereas the Fe(III) complex with the highest stability (with three bidentate ligands) possesses a ΔGf0 of −58.9 kcal/mol. These complexes can significantly reduce the rate constant of the first step of the Haber-Weiss cycle with both O2•− and ASC−. In the case of the copper-containing reaction, the rates are reduced up to 9.70 × 103 and 4.09 × 1013 times, respectively. With iron, the rates become 1.78 × 103 and 4.45 × 1015 times smaller, respectively. Thus, PM presents significant secondary antioxidant activity since it is able to inhibit the production of ·OH radicals. This work concludes a series of studies on secondary antioxidant activity and allows potentially new glycation inhibitors to be investigated and compared relative to both PM and AG.

Pyridoxamine treatment ameliorates large artery stiffening and cerebral artery endothelial dysfunction in old mice

“…An alternative mechanism for the beneficial effects of on large artery stiffness is by the antioxidant effects of pyridoxamine. 8,9 Antioxidants are known to reduce large artery stiffness in older humans and animals. 42,43 Due to the lack of differences in AGEs between treatment groups in this study, we surmise that the mechanism of pyridoxamine is mainly mediated via its antioxidant properties.…”

“…6,7 Pyridoxamine also has antioxidant properties that may also contribute to its beneficial effects on arterial stiffness and function. 8,9 Other forms of vitamin B6, including the most common pyridoxine, do not have these same actions as pyridoxamine. 7,10,11 While the evidence for cardiovascular benefits of vitamin B6 supplementation are inconsistent, 12–14 these large clinical trials are all performed with pyridoxine and are missing the benefits specific to pyridoxamine.…”

Oxidation of l -leucine amino acid initiated by hydroxyl radical: are transition metal ions an enhancement factor?

“…[23][24][25][26]. In this study, the high-spin states of hydrated Fe(II) and Fe(III) ions being 5 and 6, respectively, were used as recommended by several works in the literature [25][26][27][28][29][30].…”

“…To characterize the complexation reactions, the equilibrium constants, K f commonly called the formation constants, were also calculated by equation (2.4) [25,28,31]. K f ¼ e ÀðDrG 0 =RTÞ : ð2:4Þ…”

Influence of transition metal ions on the oxidation of L-proline amino acid initiated by HO● radical in the aqueous phase

“…[38][39][40][41][42] The high-spin states of hydrated Fe(II) and Fe(III) ions in this study were equal to 5 and 6, respectively. 23,38,41,[43][44][45][46] The kinetics of the HO-initiated oxidation of Pro, which occurs as FHT reactions in water, were studied using the pre-reactive complexes scheme proposed by Singleton and Cvetanovic 47 . Briefly, a two-step mechanism was considered:…”