Determination of the C4H Bond Dissociation Energies of NADH Models and Their Radical Cations in Acetonitrile

Abstract Heterolytic and homolytic bond dissociation energies of the C4H bonds in ten NADH models (seven 1,4‐dihydronicotinamide derivatives, two Hantzsch 1,4‐dihydropyridine derivatives, and 9,10‐dihydroacridine) and their radical cations in acetonitrile were evaluated by titration calorimetry and electrochemistry, according to the four thermodynamic cycles constructed from the reactions of the NADH models with N , N , N ′, N ′‐tetramethyl‐ p ‐phenylenediamine radical cation perchlorate in acetonitrile (note: C9H bond rather than C4H bond for 9,10‐dihydroacridine; however, unless specified, the C9H bond will be described as a C4H bond for convenience). The results show that the energetic scales of the heterolytic and homolytic bond dissociation energies of the C4H bonds cover ranges of 64.2–81.1 and 67.9–73.7 kcal mol −1 for the neutral NADH models, respectively, and the energetic scales of the heterolytic and homolytic bond dissociation energies of the (C4H) .+ bonds cover ranges of 4.1–9.7 and 31.4–43.5 kcal mol −1 for the radical cations of the NADH models, respectively. Detailed comparison of the two sets of C4H bond dissociation energies in 1‐benzyl‐1,4‐dihydronicotinamide (BNAH), Hantzsch 1,4‐dihydropyridine (HEH), and 9,10‐dihydroacridine (AcrH 2 ) (as the three most typical NADH models) shows that for BNAH and AcrH 2 , the heterolytic C4H bond dissociation energies are smaller (by 3.62 kcal mol −1 ) and larger (by 7.4 kcal mol −1 ), respectively, than the corresponding homolytic C4H bond dissociation energy. However, for HEH, the heterolytic C4H bond dissociation energy (69.3 kcal mol −1 ) is very close to the corresponding homolytic C4H bond dissociation energy (69.4 kcal mol −1 ). These results suggests that the hydride is released more easily than the corresponding hydrogen atom from BNAH and vice versa for AcrH 2 , and that there are two almost equal possibilities for the hydride and the hydrogen atom transfers from HEH. Examination of the two sets of the (C4H) .+ bond dissociation energies shows that the homolytic (C4H) .+ bond dissociation energies are much larger than the corresponding heterolytic (C4H) .+ bond dissociation energies for the ten NADH models by 23.3–34.4 kcal mol −1 ; this suggests that if the hydride transfer from the NADH models is initiated by a one‐electron transfer, the proton transfer should be more likely to take place than the corresponding hydrogen atom transfer in the second step. In addition, some elusive structural information about the reaction intermediates of the NADH models was obtained by using Hammett‐type linear free‐energy analysis.