Revisiting the HO●-initiated oxidation of L-proline amino acid in the aqueous phase – Influence of transition metal ions

The oxidation of L-proline (Pro) by HO● radical in water and the influence of transition metal ions on this process has been revisited by using the density functional theory (DFT) method at the M05-2X/6-311++G(3df,3pd)//M05-2X/6-311++G(d,p) level of theory at the temperature of 298.15 K. HO●-initiated oxidation of Pro via hydrogen atom transfer (HAT) reactions is more favourable at the b- and g-carbon than at the a- and d-carbon. The total branching ratios are 44.6% and 39.5% for the β- and γ-carbon and 11.5% and 4.2% for the a- and d-carbon, respectively. The overall rate constant at 298.15 K is 6.04 × 108 M-1 s-1. In addition, Pro tends to form the stable mono- and bi-dentate complexes with both Fe and Cu ions via the –COO functional group of dipole-salt form. The most stable Cu(II)-Pro complexes have high potential oxidant risks by enhancing the HO● radical formation in the presence of reducing agents such as superoxide anion or ascorbate anion. Besides, the complexes of the metal at a high oxidation state, i.e., Fe(III)-Pro and Cu(II)-Pro, show their ability to be oxidized by HO● radical via HAT reactions but with a lower rate constant than that of free Pro. Unsurprisingly, the oxidation enhancement is insignificant for SET reactions with almost negligible rate constants. In contrast, the rate constants of SET reactions of low oxidation state complexes (i.e., Fe(II)-Pro and Cu(I)-Pro) are faster than the oxidation rate of free ligands, and thus, these complexes promote the oxidation of Pro.