posted on 2023-12-29, 12:33authored byZijun Wu, Robynne Vlaming, Michael Donohoe, Derek A. Pratt
The reactions of organoboranes with
peroxyl radicals are key to
their use as radical initiators for a vast array of radical chain
reactions, particularly at low temperatures where high stereoselectivity
or regioselectivity is desired. Whereas these reactions generally
proceed via concerted homolytic substitution (SH2) mechanisms,
organoboranes that bear groups that can stabilize tetracoordinate
boron radical “ate” complexes (e.g., catecholboranes)
undergo this reaction via a stepwise addition/fragmentation sequence
and serve as useful stoichiometric alkyl radical precursors. Here
we show that arylboronic esters and amides derived from catecholborane
and diaminonaphthaleneborane, respectively, are potent radical-trapping
antioxidants (RTAs). Mechanistic studies reveal that this is because
the radical “ate” complexes derived from peroxyl radical
addition to boron are sufficiently persistent to trap another radical
in an interrupted SH2 reaction. Remarkably, the reactivity
of these organoboranes as inhibitors of autoxidation was shown to
translate from simple hydrocarbons to the phospholipids of biological
membranes such that they can inhibit ferroptosis, the cell death modality
driven by lipid autoxidation and relevant in neurodegeneration and
other major pathologies. The unique mechanism of these organoboranes
is one of only a handful of RTA mechanisms that are not based on H-atom
transfer processes and provide a new dimension to boron chemistry
and its applications.