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

Abstract

The oxidation of L-proline (Pro) amino acid by HO • radical and the influence of transition metal ions on this process have been investigated 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 in the aqueous phase. The results show that Pro can be oxidized by HO • radical via formal hydrogen transfer (FHT) reactions at multiple sites, with the highest branching ratio found at hydrogen atoms H10 (30.04%) and H12 (25.60%). The overall rate constant at 298.15K is determined as 6.04 × 10 8 M -1 s -1 , and its expression from 250 to 400K is k=1.634×T 2.990 ×exp[1.591(kcal mol -1 )/RT] M -1 s -1 . In addition, Pro tends to form the stable mono-and bidentate complexes with both Fe and Cu ions via the-COO functional group of dipole-salt form, which significantly increases when the concentration of Pro doubles. The most stable Cu(II)-Pro complexes have high potential oxidant risks by enhancing the HO • radical formation when reducing agents such as superoxide anion, or ascorbate anion are available. Besides, the oxidant reaction of the high oxidation state complexes, including Fe(III)-Pro and Cu(II)-Pro, by HO • radical as FHT reactions have a lower rate constant than that of free-ligand, while the ones for SET reactions is extremely low even though they are higher than that of free-ligand. As a result, the Pro's oxidation enhancement of these complexes is negligible. In contrast, the rate constants of SET reactions of low oxidation state complexes (i.e., Fe(II)-Pro and Cu(I)-Pro) are likely to be many times faster than the oxidation rate of free ligand, and thus, these complexes promote the oxidation of Pro. Finally, the FHT chemical nature of HO-initiated oxidation for free Pro, Fe(III)-Pro, and Cu(II)-Pro complexes are evaluated to determine whether these processes occur via hydrogen atom transfer (HAT) or proton-coupled electron transfer (PCET).