A Computational Analysis of the Proton Affinity and the Hydration of TEMPO and Its Piperidine Analogs

The study investigated the impact of protonation and hydration on the geometry of nitroxide radicals using B3LYP and M06-2X methods. Results indicated that TEMPO exhibited the highest proton affinity in comparison to TEMPOL and TEMPONE. Two pathways contribute to hydrated protonated molecules. TEMPO shows lower first enthalpies of hydration (ΔH_1-M), indicating stronger H-bonding interactions, while TEMPONE shows higher values, indicating weaker interactions with H₂O. Solvent effects affect charge distribution by decreasing their atomic charge. Spin density (SD) is primarily concentrated in the NO segment, with minimal water molecule contamination. Protonation increases SD on N-atom, while hydration causes a more pronounced redistribution for water molecules. The stability of the dipolar structure (>N⋅⁺-O^-) is evident in SD redistributions. The frontier molecular orbital (FMO) analysis of TEMPONE reveals a minimum E_HOMO-LUMO gap (E_H-L), enhancing the piperidine ring's reactivity. TEMPO is the most nucleophilic species, while TEMPONE exhibits strong electrophilicity. Transitioning from NO radicals to protonated forms increases the E_H-L gap, indicating protonation stabilizes FMOs. Increased water molecules make the molecule less reactive, while increasing hydration decreases this energy gap, making the molecule more reactive. A smaller E_H-L gap indicates the compound becomes softer and more prone to electron density and reactivity changes.