Chapter 25, Problem 25.19YT

Interpretation Introduction

Interpretation:

It is stated that α-tocopherol is a natural antioxidant that terminates lipid peroxidation by donating H to a lipid radical ($\text{R•}$). This hydrogen abstraction step is shown, as are two resonance structures of the resulting phenoxy radical. The curved arrows for the hydrogen abstraction step and also for the conversion of the first resonance structure into the second are to be added. The reason α-tocopherol is such an effective antioxidant is to be explained.

Concept introduction:

In the body, free radicals play important roles in cell signaling and protecting against invading bacteria. Because they are highly reactive, however, these free radicals can lead to unwanted side reactions that damage or kill cells. The hydroxyl radical ($\text{HO•}$) is particularly damaging via a process called lipid peroxidation. We know that the lipid bilayer of a cell membrane is made up of phospholipids, each containing two nonpolar hydrocarbon tails. As shown below on the left, cis $\text{C=C}$ double bonds are common features of the hydrocarbon tails, and the allylic $\text{H}$ atoms are susceptible to hydrogen abstraction.

As shown in the scheme above on the right, hydrogen abstraction produces an allylic radical, which subsequently undergoes radical coupling with a molecule of ${\text{O}}_{\text{2}}$ to produce a lipid peroxyl radical. The lipid peroxyl radical then abstracts an $\text{H}$ atom from another phospholipid, resulting in a lipid hydroperoxide and another lipid radical that can go on to continue the propagation cycle.

Lipid peroxides and the compounds they produce in subsequent reactions are very toxic. Fortunately, vitamin E (which is α-tocopherol), found abundantly in foods such as almonds, spinach, and avocados, is a natural antioxidant that is one of the body’s most important defenses against lipid peroxidation. A lipid radical can readily abstract the phenolic $\text{H}$ from vitamin E, leaving behind a relatively unreactive phenoxy radical (see Your Turn 25.19). In so doing, the lipid radical is converted to a closed-shell species, and the propagation cycle is terminated.