Atropisomerism
of the Asn α Radicals Revealed
by Ramachandran Surface Topology
- Publication date
- Publisher
Abstract
C radicals are typically trigonal
planar and thus achiral, regardless
of whether they originate from a chiral or an achiral C-atom (e.g.,
C–H + <sup>•</sup>OH → C• + H<sub>2</sub>O). <b>Oxidative stress</b> could initiate radical formation
in proteins when, for example, the H-atom is abstracted from the Cα-carbon
of an amino acid residue. Electronic structure calculations show that
such a radical remains achiral when formed from the achiral Gly, or
the chiral but small Ala residues. However, when longer side-chain
containing proteogenic amino acid residues are studied (e.g., Asn),
they provide radicals of axis chirality, which in turn leads to <b>atropisomerism</b> observed for the first time for peptides. The
two <b>enantiomeric</b> extended backbone <b>structures</b>, •β<sub>L</sub> and •β<sub>D</sub>, interconvert
via a pair of <b>enantiotopic reaction paths</b>, monitored
on a 4D Ramachandran surface, with two distinct transition states
of very different <i>Gibbs</i>-free energies: 37.4 and 67.7
kJ/mol, respectively. This discovery requires the reassessment of
our understanding on radical formation and their conformational and
stereochemical behavior. Furthermore, the atropisomerism of proteogenic
amino acid residues should affect our understanding on radicals in
biological systems and, thus, reframes the role of the D-residues
as markers of <b>molecular aging</b>
