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.

All geometry optimizations and vibrational frequency calculations for reactants, transition states, pre-reactive complexes, post-reactive complexes and products were performed by Gaussian 16 Rev. A.03 package in aqueous phase using M05-2X functional and 6-311++G(d,p) basis set. Accuracy of the energy values was then improved by single point calculations at M05-2X/6-311++G(3df,2pd) level of theory.

The standard enthalpies (ΔrH0) and Gibbs free energies (ΔrG0) of the reactions forming complexes were calculated as the differences between total reactant and total product molar enthalpies and Gibbs free energies, respectively. The kinetics calculations of the redox reactions as well as the oxidation reaction of Leu by  HO^● radical were determined by using conventional transition state theory (TST) in aqueous phase at 298.15 K that was employed in KiSThelP program.

The readme file contains the Cartesian coordination and thermochemistry properties of the Leu in two studied forms (Table SI1), optimized structures of five Leu 1:1 metal-to-ligand stoichiometric ratio complexes with Fe(III)/Fe(II) ions (Table SI2) and Cu(II)/Cu(I) ions (Table SI3); the thermodynamic parameters of the complexation reactions of these complexes (Table SI4); and the transition states (TSs) of FHT reactions of Leu toward HO● radical (Table SI5). All structures are optimized and calculated for thermochemical parameter values in water at the M05-2X/6-311++G(3df,2dp)//M05-2X/6-311++G(d,p) level of theory.