Theoretical Study of the Iron Complexes with Lipoic and Dihydrolipoic Acids: Exploring Secondary Antioxidant Activity

Abstract

The thermodynamic stability of twenty-nine Fe(III) complexes with various deprotonated forms of lipoic (LA) and dihydrolipoic (DHLA) acids, with coordination numbers 4, 5 and 6, is studied at the M06(SMD)/6-31++G(d,p) level of theory in water under physiological pH conditions at 298.15 K. Even though the complexes with LA- are more stable than those with DHLA−, the most thermodynamically stable Fe(III) complexes involve DHLA2−. The twenty-four exergonic complexes are used to evaluate the secondary antioxidant activity of DHLA and LA relative to the Fe(III)/Fe(II) reduction by O2•− and ascorbate. Rate constants for the single-electron transfer (SET) reactions are calculated. The thermodynamic stability of the Fe(III) complexes does not fully correlate with the rate constant of their SET reactions, but more exergonic complexes usually exhibit smaller SET rate constants. Some Cu(II) complexes and their reduction to Cu(I) are also studied at the same level of theory for comparison. The Fe(III) complexes appear to be more stable than their Cu(II) counterparts. Relative to the Fe(III)/Fe(II) reduction with ascorbate, DHLA can fully inhibit the formation of •OH radicals, but not by reaction with O2•−. Relative to the Cu(II)/Cu(I) reduction with ascorbate, the effects of DHLA are moderate/high, and with O2•− they are minor. LA has minor to negligible inhibition effects in all the cases considered.

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

“…Their thermodynamic data and structures are reported in the Supporting Information along with their Cartesian coordinates (see the species labelled {F3} to {F17} ). This was also the methodology followed in previous publications [ 22 , 23 , 29 , 44 ].…”

“…Moreover, other groups have investigated from a theoretical perspective the antioxidant activity of several organic molecules in the presence of cupric ions [ 44 , 49 , 50 ]. In addition to this, our group has recently published four papers in which the antioxidant activity of AG and dihydrolipoic acid is examined [ 22 , 23 , 29 , 44 ]. We found that these ligands can chelate both Cu(II) and Fe(III) and greatly reduce the rate constant of the first step of the Haber-Weiss cycle when the reductant is ascorbate, but not when it is .…”

“…PM, upon coordination with Cu(II), is able to inhibit ∙OH radical formation when reacting with ASC − , and can do the same when reacting with if in a significant concentration to favour the formation of {A11} . In our previous studies, the highest reduction we have observed when is the reductant was of 3.4 times with dihydrolipoic acid [ 29 ].…”

“…However, it is known experimentally that both AG and PM can slow down this reaction [ 6 , 28 ]. In our previous publications, we showed that both AG and dihydrolipoic acid can slow down the reaction rate of the first step of the Haber–Weiss cycle with both metals when the reducing agent is ASC − [ 22 , 23 , 29 ]. However, they exhibited no secondary antioxidant activity when the reducing agent is the superoxide radical anion (O 2 · − ).…”

Antioxidant and UV-radiation absorption activity of aaptamine derivatives – Potential application for natural organic sunscreens

“…61 Regarding to Cu(II) ion, its complexation with the potential antioxidant compounds could sometime prevent the reduction process that forms Cu(I) ion and HO  radical. The fact was that, several potential antioxidants show good copper ions chelating abilities were reported with aminoguanidine, 62 pyridoxamine, 63 lipoic and dihydrolipoic acids, 64 purine, 18 citric acid, 65 D-penicillamine, 66 2-hydroxymelatonin and 4-hydroxymelatonin. 16 In this study, the Cu(II) complexes formed by the chelating process of the three aaptamines at different possible chelation sites in water phase are evaluated in Figure 6, while the similar complexes with Cu(I) ion are also presented in As can be seen in Figure 6, all the three aaptamine compounds show spontaneous and favorable Cu(II) ion chelating activities with negative H 0 and G 0 values.…”