Oxidation of L-leucine amino acid initiated by HO● radical - Are transition metal ions an enhancement factor?

Hydroxyl radical (HO^●) formation initiated by the Fenton-type reactions of Fe and Cu complexes of L-leucine (Leu) amino acid, as well as its oxidation reaction by HO^● were computationally investigated by using the density functional theory (DFT) method at the M05-2X/6-311++G(3df,2pd)//M05-2X/6-311++G(d,p) level of theory in the aqueous phase. The results showed that dipole-salt is the main form of Leu in the physiological condition. Leu exhibits high chelating potential towards both Fe(III)/Fe(II) and Cu(II)/Cu(I) ions with the most favorable coordinating positions at two oxygen atoms of the –COO functional groups. Furthermore, the Leu-ions complexes show a high risk of HO^● formation via Fenton-like reactions, especially when ascorbate anion exists in the environment as a reducing agent. Finally, the oxidation reaction of L-leucine by HO^● demonstrated a relatively high overall apparent reaction rate – k_overall being 1.18 × 10⁹ M^-1s^-1, in which formal hydrogen transfer (FHT) reactions of the dipole-salt form occur as the primary mechanism. Consequently, the Leu oxidation by HO^● radical can be promoted by the Fenton-reaction enhancement of its transition metal complexes.