Charge at the migrating hydrogen in the transition state of hydride transfer reactions from CH groups to hydride acceptors. Dynamics of the redox‐couple NADH‐NAD⁺

Abstract

ABSTRACT:We consider the controversial conclusions of the charge at the migrating hydrogen in the transition state of hydride-transfer reactions from CH-groups to hydride acceptors. Quantum chemical calculations were performed on elementary organic reactions involving carbenium ions, which can be considered as hydride acceptors. We also discuss the biochemical hydride-transfer reactions in which the coenzyme NADH-NAD ϩ plays an important role. With the calculations and the experimental model systems, an answer is given for the stereospecificity of the hydride transfer. Generally, the hydride transfer occurs via a trigonal pyramidal geometry in which the transferred hydride of the CH-group is located in the axial position. In the case of the coenzyme NADH-NAD ϩ , the hydride transfer is coupled with an out-of-plane orientation of the carboxamide group of the pyridinium moiety, resulting in an increased stereospecificity.

Differences of pH-Dependent Mechanisms on Generation of Hydride Donors using Ru(II) Complexes Containing Geometric Isomers of NAD+ Model Ligands: NMR and Radiolysis Studies in Aqueous Solution

“…In biological systems NAD + /NADH acts as a mediator for two electrons and a proton, equivalent to a hydride ion (H − ) to reduce CO 2 . Increasing numbers of nicotinamide adenine dinucleotide (NADH) analogues, such as 9-substituted 10-methyl-9,10-dihydroacridine and 1-benzyl-1,4-dihydronicotinamide, have been examined for their photochemical and thermal reactivity. − Most of the reactions mediated with NADH models, however, are limited to stoichiometric reactions due in part to the facile dimerization of the radical species (the NAD • equivalent). − The introduction of transition metals into NADH analogues − imbues these systems with new characteristics, such as long-lived excited states, multiple oxidation states, catalytic activity, and efficient light absorption over a wide spectral range.…”

Redox Specificity of 2-Hydroxyacid-Coupled NAD+/NADH Dehydrogenases: A Study Exploiting “Reactive” Arginine as a Reporter of Protein Electrostatics

“…Lactate dehydrogenases (LDHs) and malate dehydrogenases (MDHs) are the prototypical 2-hydroxyacid dehydrogenases relatively better characterized in their redox variations. LDH is a tetramer over two kinds of polypeptide chains, M and H, which are random in their association as tetramers [13] – [15] . The M4 and H4 variants, the extremes of the association, are recognized for their role in Cori cycle involving flow of energy charge at organism level on basis of pyruvate/lactate coupled inter-conversion between NAD + and NADH [8] .…”

A comparative theoretical study of the hydride transfer mechanisms during LiAlH 4 and LiBH 4 reductions

“…Hydride transfer is a key process in hydride reduction and so, to elucidate the associated reaction mechanism, it is important to understand the hydride reduction mechanism. In previous works, the hydride transfer mechanisms in many biological and organic reduction systems were investigated using either experimental or theoretical approaches [13][14][15][16][17][18][19][20][21][22][23][24]. Although these mechanisms have not yet been fully explained due to the variety of possible pathways involving the overall transfer of two electrons and one proton, the following hydride transfer mechanisms have been proposed: (1) direct transfer of a hydride ion (H -) in a single step, (2) two-step transfer of an electron before or after the transfer of a hydrogen atom and (3) transfer of two electrons and one proton in three separate steps.…”