Tocopheramines and tocotrienamines as antioxidants: ESR spectroscopy,rapid kinetics and DFT calculations

Tocopheramines (TNH₂) and tocotrienamines (T₃NH₂) are analogues of tocopherols (TOH) and tocotrienols in which phenolic OH is replaced by NH₂. It was shown in previous studies that TNH₂ and T₃NH₂ act as potent antioxidants. In this study we compared the one-electron oxidation of TNH₂/T₃NH₂ by diphenyl picryl hydrazyl (DPPH) and galvinoxyl (GOX) radicals with the one of α-TOH as a reference compound using ESR spectroscopy, stopped flow spectrophotometry and density functional theory (DFT) calculations. ESR spectroscopy revealed the presence of tocopheramine radicals during electrochemical oxidation of α-TNH₂. Kinetic measurements demonstrated that in apolar n-hexane TNH₂/T₃NH₂ derivatives reacted two to three orders of magnitude slower than α-TOH with the model radicals. DFT calculations indicated that this correlates well with the higher bond dissociation energy (BDE) for N–H in TNH₂ than for O–H in α-TOH in pure H-atom transfer (HAT). In the more polar medium ethanol TNH₂/T₃NH₂ derivatives partially reacted faster than α-TOH depending on the reaction partner. DFT calculations suggest that this is due to reaction mechanisms alternative to HAT. According to thermochemistry data sequential proton loss and electron transfer (SPLET) is more favored for α-TOH in ethanol than for TNH₂. Therefore, for TNH₂ a contribution of the alternative mechanism of sequential electron transfer–proton transfer (SET–PT) could be a possible explanation. These data show that the antioxidant reactivity strongly depends on the structure, reaction partners and environment. According to these findings TNH₂/T₃NH₂ should be superior as antioxidants over α-TOH in polar head group regions of membranes but not in the apolar core of lipid bilayers.