The Tightness Contribution to the Brønsted α for Hydride Transfer between NAD⁺ Analogues

Abstract

It has been shown that the rate of symmetrical hydride transfer reaction varies with the hydride affinity of the (identical) donor and acceptor. In that case, Marcus theory of atom and group transfer predicts that the Brønsted alpha depends on the location of the substituent, whether it is in the donor or the acceptor, and the tightness of the critical configuration, as well as the resemblance of the critical configuration to reactants or products. This prediction has now been confirmed for hydride transfer reactions between heterocyclic, nitrogen-containing cations, which can be regarded as analogues of the enzyme cofactor, nicotinamide adenine dinucleotide (NAD+). A series of reactions with substituents in the donor gives Brønsted alpha of 0.67 +/- 0.03 and a tightness parameter, tau, of 0.64 +/- 0.06. With substituents in the acceptor alpha = 0.32 +/- 0.03 and tau = 0.68 +/- 0.08. The reactions are all spontaneous, with equilibrium constants between 0.4 and 3 x 10(4), and the two sets span about the same range of equilibrium constants. The two tau values are essentially identical with an average value of 0.66 +/- 0.05. These results can be semiquantitatively mimicked by rate constants calculated for a linear, triatomic model of the reaction. Variational transition state theory and a physically motivated but empirically calibrated potential function were used. The computed rate constants generate an alpha value of 0.56 if the hydride affinity of the acceptor is varied and an alpha of 0.44 if the hydride affinity of the donor is varied. The calculated kinetic isotope effects are similar to the measured values. A previous error in the Born charging term of the potential function has been corrected. Marcus theory can be successfully fitted to both the experimental and computed rate constants, and appears to be the most compact way to express and compare them. The success of the linear triatomic model in qualitatively reproducing these results encourages the continued use of this easily conceptualized model to think about group, ion, and atom transfer reactions.

Effect of Basic Site Substituents on Concerted Proton–Electron Transfer in Hydrogen-Bonded Pyridyl–Phenols

“…In a purely classical picture, this could reflect an asymmetry in the reaction coordinate, with the transition structure involving more proton transfer. 60 In the context of PCET theory (eq 1), changing the pyridine substituent could affect k s CPET via changes in the intrinsic barriers λ or quantum mechanical prefactor terms V el and FC . This is discussed in more detail below.…”

Outer‐Sphere 2 e−/2 H+ Transfer Reactions of Ruthenium(II)‐Amine and Ruthenium(IV)‐Amido Complexes

“…Thus, the Ru IV / Ru II system resembles the 2 e − /2 H + donor N 2 H 2 (HN=NH, diazene) in some ways, which is known to mediate symmetrical concerted transfers of two hydrogen atoms (2 e − /2 H + ) to C−C π‐bonds . The most common concerted multielectron PCET processes are hydride transfers (2 e − /1 H + ) . There is debate over whether Noyori‐type ketone/alcohol interconversions occur by concerted H − /H + transfers .…”

The saturated five‐membered heterocyclic molecules as organic hydride donors: a computational study

“…Considering 1‐benzyl‐1,4‐dihydronicotinamide (BNAH), Hantzch ester and 9,10‐dihydroacridine (AcrH 2 ) as models of NADPH to probe the mechanism of hydride transfer has been employed by several research groups . In biochemistry hydride transfer, involving acceptor coenzyme NAD + and NADP + is common and consists of reaction catalyzed by a variety of dehydrogenases . The reduced form of NADH plays a vital role in numerous bioreductions by transferring a hydride ion or electrons to the surrounding substrate to comprehend the vital functions of the NADH coenzyme in living bodies .…”