A DFT study of the antioxidant potency of α-tocopherol and its derivatives: PMHC, Trolox, and α-CEHC

In this research, antioxidant potency (in terms of peroxyl radical scavenging and catalytic iron ions sequestration) of α-tocopherol and its analogues, has been theoretically investigated. A DFT based kinetic estimation of HOO• radical scavenging potency of PMHC (lipophilic α-TOH derivative) and Trolox (hydrophilic α-TOH derivative) was performed in eight solvents of different polarity. Calculations employing M06-2X functional, accompanied by 6–311++G(d,p) basis set and SMD solvation model, were found as more accurate in reproducing experimentally determined rate constants than M05-2X functional. Rate constant of Trolox in pentyl ethanoate also was estimated by using Snelgrove − Ingold equation and Abraham’s β2H solvent parameter. Scavenging of CH3OO• and HOO• radicals, which is influenced by location, orientation, and dynamics of α-TOH and its derivatives in the membrane lipid bilayer, was estimated by using M06-2X functional. Position of α-TOH phenolic OH group is opposite to that of its metabolite α-CEHC: α-TOH’s OH group is located at the membrane-water interface, and α-CEHC’s OH group is deeply buried into the bilayer. In the aqueous phase both fHAT and SET were investigated, and inside the bilayer only fHAT was considered as feasible. The spontaneous disproportionation of HOO•/O2•− in aqueous solutions should be taken into account to predict potency of antioxidant in scavenging of HOO• radicals. Iron chelating ability of α-TOH and α-CEHC was also investigated. Obtained results indicate α-CEHC, α-tocopherol final catabolite, as more potent scavenger of CH3OO• and HOO• radicals and iron ions chelator than the parent molecule.