One-step versus stepwise mechanism in protonated amino acid-promoted electron-transfer reduction of a quinone by electron donors and two-electron reduction by a dihydronicotinamide adenine dinucleotide analogue. Interplay between electron transfer and hydrogen bonding

Semiquinone radical anion of 1-(p-tolylsulfinyl)-2,5-benzoquinone (TolSQ^•-) forms a strong hydrogen bond with protonated histidine (TolSQ^•-/His·2H⁺), which was successfully detected by electron spin resonance. Strong hydrogen bonding between TolSQ ^•- and His·2H⁺ results in acceleration of electron transfer (ET) from ferrocenes [R₂Fc, R = C₅H ₅, C₅H₄(n-Bu), C₅H₄Me] to TolSQ, when the one-electron reduction potential of TolSQ is largely shifted to the positive direction in the presence of His·2H⁺. The rates of His·2H⁺-promoted ET from R₂Fc to TolSQ exhibit deuterium kinetic isotope effects due to partial dissociation of the N-H bond in His·2H⁺ at the transition state, when His·2H ⁺ is replaced by the deuterated compound (His·2D ⁺-d₆). The observed deuterium kinetic isotope effect (k_H/k_D) decreases continuously with increasing the driving force of ET to approach k_H/k_D = 1.0. On the other hand, His·2H⁺ also promotes a hydride reduction of TolSQ by an NADH analogue, 9,10-dihydro-10-methylacridine (AcrH₂). The hydride reduction proceeds via the one-step hydride-transfer pathway. In such a case, a large deuterium kinetic isotope effect is observed in the rate of the hydride transfer, when AcrH₂ is replaced by the dideuterated compound (AcrD₂). In sharp contrast to this, no deuterium kinetic isotope effect is observed, when His·2H⁺ is replaced by His·2D⁺-d₆. On the other hand, direct protonation of TolSQ and 9,10-phenanthrenequinone (PQ) also results in efficient reductions of TolSQH⁺ and PQH⁺ by AcrH₂, respectively. In this case, however, the hydride-transfer reactions occur via the ET pathway, that is, ET from AcrH₂ to TolSQH⁺ and PQH⁺ occurs in preference to direct hydride transfer from AcrH₂ to TolSQH⁺ and PQH⁺, respectively. The AcrH₂ ^•+ produced by the ET oxidation of AcrH₂ by TolSQH⁺ and PQH⁺ was directly detected by using a stopped-flow technique.