Quantitative Estimation Of The Hydrogen-Atom-Donating Ability Of 4-Substituted Hantzsch Ester Radical Cations

The purpose of this study is to investigate thermodynamic and kinetic properties on the hydrogen-atom-donating ability of 4-substituted Hantzsch ester radical cations (XRH center dot+), which are excellent NADH coenzyme models. Gibbs free energy changes and activation free energies of 17 XRH center dot+ releasing H-center dot [denoted as.GHDo (XRH center dot+) and Delta G(HD)(not equal) (XRH center dot+)] were calculated using density functional theory (DFT) and compared with that of Hantzsch ester (HEH2) and NADH..GHDo (XRH center dot+) range from 19.35 to 31.25 kcal/mol, significantly lower than that of common antioxidants (such as ascorbic acid, BHT, the NADH coenzyme, and so forth). Delta G(HD)(not equal) (XRH center dot+) range from 29.81 to 39.00 kcal/mol, indicating that XRH center dot+ spontaneously releasing H-center dot are extremely slow unless catalysts or active intermediate radicals exist. According to the computed data, it can be inferred that the Gibbs free energies and activation free energies of the core 1,4-dihydropyridine radical cation structure (DPH center dot+) releasing H-center dot [Delta G(HD)(o) (DPH center dot+) and.GHD. (DPH center dot+)] should be 19-32 kcal/mol and 29-39 kcal/mol in acetonitrile, respectively. The correlations between the thermodynamic driving force [Delta G(HD)(o) (XRH center dot+)] and the activation free energy [Delta G(HD)(not equal) (XRH center dot+)] are also explored. Gibbs free energy is the important and decisive parameter, and.GHD. (XRH center dot+) increases in company with the increase of.GHDo (XRH center dot+), but no simple linear correlations are found. Even though all XRH center dot+ are judged as excellent antioxidants from the thermodynamic view, the computed data indicate that whether XRH center dot+ is an excellent antioxidant in reaction is decided by the R substituents in 4-position. XRH center dot+ with nonaromatic substituents tend to release R-center dot instead of H-center dot to quench radicals. XRH center dot+ with aromatic substituents tend to release H-center dot and be used as antioxidants, but not all aromatic substituted Hantzsch esters are excellent antioxidants.