Design principles for α-tocopherol analogues

Abstract

An (RO)B3LYP/LANL2DZdp//B3LYP/LANL2DZ model for the prediction of the homolytic bond dissociation enthalpy (BDE) and adiabatic ionisation potential (IP) of phenolic antioxidants containing heavy chalcogens has been developed. The model has been used to probe the relationship between geometry, chalcogen substitution and activity for a series of alpha-tocopherol analogues of varying ring size. From this, a series of design principles for cyclic antioxidants has emerged, embodied by the compound 4-hydroxy-2,2,3,5,6-pentamethylbenzoselenete (4c). This compound is predicted to have a BDE comparable to alpha-tocopherol, and should act in a dual chain-breaking and hydroperoxide-decomposing manner, by analogy with other selenide antioxidants. The stability of chalcogen-substituted benzoxetes was considered, and the as yet unsynthesised benzotelluretes are predicted to be stable. Finally, an attempt was made to determine antioxidant mechanism by considering calculated BDE and IP data together with experimental rate data.

Resveratrol-based benzoselenophenes with an enhanced antioxidant and chain breaking capacity

“…33 This level has been previously adopted to calculate the geometries and bond dissociation enthalpies of S, Se and Te containing phenols. 34 The nature of the located stationary points was determined by computation of harmonic vibrational frequencies (zero imaginary frequency). The enthalpies at 298 K were computed at the stationary points from frequency calculations, after scaling the results by a factor of 0.9809.…”

Ultrafast Adiabatic Photodehydration of 2‐Hydroxymethylphenol and the Formation of Quinone Methide

“…It is well known that benzoxete 4 is a highly strained molecule (38 kcal mol −1 ) that has not yet been detected at room temperature. It has been detected by cryogenic measurements, formed by carbene insertion into a phenolic OH bond and in the photoelimination of CO .…”

Asymmetric Synthesis and Biological Activity of nor‐α‐Tocopherol, a New Vitamin E Analogue

“…[6,7] In contrast, replacement of the sixmembered heterocycle with a five-membered ring (see [5][6][7][8] led to greater radical chain-breaking capacities in a two-phase lipid peroxidation model system. [7,8] More recent studies have reported on the replacement of the chiral side chain in 1 by shorter units with polar functional groups (see, for example, 9 and 10). [9] These compounds show remarkably increased antioxidant potencies in relation to 1.…”