Oxidations of NADH Analogues by cis-[Ru^IV(bpy)₂(py)(O)]²⁺ Occur by Hydrogen-Atom Transfer Rather than by Hydride Transfer

Oxidations of the NADH analogues 10-methyl-9,10-dihydroacridine (AcrH₂) and N-benzyl 1,4-dihydronicotinamide (BNAH) by cis-[Ru^IV(bpy)₂(py)(O)]²⁺ (Ru^IVO²⁺) have been studied to probe the preferences for hydrogen-atom transfer vs hydride transfer mechanisms for the C−H bond oxidation. ¹H NMR spectra of completed reactions of AcrH₂ and Ru^IVO²⁺, after more than ∼20 min, reveal the predominant products to be 10-methylacridone (AcrO) and cis-[Ru^II(bpy)₂(py)(MeCN)]²⁺. Over the first few seconds of the reaction, however, as monitored by stopped-flow optical spectroscopy, the 10-methylacridinium cation (AcrH⁺) is observed. AcrH⁺ is the product of net hydride removal from AcrH₂, but hydride transfer cannot be the dominant pathway because AcrH⁺ is formed in only 40−50% yield and its subsequent oxidation to AcrO is relatively slow. Kinetic studies show that the reaction is first order in both Ru^IVO²⁺ and AcrH₂, with k = (5.7 ± 0.3) × 10³ M^-1 s^-1 at 25 °C, ΔH^‡ = 5.3 ± 0.3 kcal mol^-1 and ΔS^‡ = −23 ± 1 cal mol^-1 K^-1. A large kinetic isotope effect is observed, k_AcrH2/k_AcrD2 = 12 ± 1. The kinetics of this reaction are significantly affected by O₂. The rate constants for the oxidations of AcrH₂ and BNAH correlate well with those for a series of hydrocarbon C−H bond oxidations by Ru^IVO²⁺. The data indicate a mechanism of initial hydrogen-atom abstraction. The acridinyl radical, AcrH^•, then rapidly reacts by electron transfer (to give AcrH⁺) or by C−O bond formation (leading to AcrO). Thermochemical analyses show that H^• and H^- transfer from AcrH₂ to Ru^IVO²⁺ are comparably exoergic:  ΔG° = −10 ± 2 kcal mol^-1 (H^•) and −6 ± 5 kcal mol^-1 (H^-). That a hydrogen-atom transfer is preferred kinetically suggests that this mechanism has an equal or lower intrinsic barrier than a hydride transfer pathway.