A Computational Investigation Revealing the Mechanisms of Photoisomerization, Amide Formation, and Spin-Trapping of a Ribonucleoside-Derived Nitrone

This computational study describes the mechanisms behind some interesting features of an acyclic nitrone obtained from the oxidation of 5-methylaminomethyl uridine (mnm⁵U), a pyrimidine ribonucleoside found at the wobble anticodon position of tRNA. The ground state geometry of this nitrone is characterized by an H-bond (1.9 Å) between the N-O and the H-O (at the 5' position of the ribofuranose ring) bonds. The S₀-S₂ and S₀-S₃ transitions at this geometry are strongly allowed. These vertical excitations are followed by relaxation passages through consecutive conical intersection (CI) channels (CI_S3/S2 → CI_S2/S1 → CI_S0/S1). The CNO moiety becomes upside or downside twisted along these pathways with a continuous decrease in the C-O bond distance, eventually leading to their respective oxaziridines. The reverse thermal pathway of oxaziridine → nitrone conversion requires overcoming a barrier of 27 kcal/mol, while the oxaziridine → amide conversion through a [1,2]-H shift requires more energy (40-47 kcal/mol). Investigations on the spin-trapping ability of this ribonucleoside-derived nitrone have indicated its possible efficiency in this field. The ΔG_rxn,_aq values of the spin-adduct formations of this nitrone with biologically important free radicals are in line with those of the best known spin-traps. These results open up a so far unexplored possibility of a new class of spin-trapping nitrones formed on tRNA oxidation.