Atropisomerism of the Asn α Radicals Revealed by Ramachandran Surface Topology

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 + ^•OH → C• + H₂O). <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_L and •β_D, 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>