Nicotinamide hydride-transfer reactions

Nickel-tin alloys electroplating, 6,14 Nicotinamide zinc complexes, 5,952 hydride-transfer reactions, 5, 954 Nicotinic acid... 

Hydride-transfer reactions involving nicotinamide cofactors 48 Commitments 55... 

Powell, M.F. and Bruice, T.C. (1983). Effect of isotope scrambling and tunneling on the kinetic and product isotope effects for reduced nicotinamide adenine dinucleotide model hydride transfer reactions. J. Am. Chem. Soc. 105, 7139-7149... 

The involvement of zinc in nicotinamide-based hydride-transfer reactions has led to numerous studies of Group IIB complexes of pyridine carboxylic acid derivatives. Cadmium complexes of 2-pyridinecarboxylic acid, 5 3-pyridinecarboxylic add497 and 3-pyridinecarboxamide498 have been reported. The crystal structure of [Cd(HC02)2L2(H20)2] (L = 3-pyridinecarboxamide) has also been described the metal is in an octahedral environment in which the amide acts as a monodentate N donor.498... 

The catalytic effect of metal ions such as Mg2+ and Zn2+ on the reduction of carbonyl compounds has extensively been studied in connection with the involvement of metal ions in the oxidation-reduction reactions of nicotinamide coenzymes [144-149]. Acceleration effects of Mg2+ on hydride transfer from NADH model compounds to carbonyl compounds have been shown to be ascribed to the catalysis on the initial electron transfer process, which is the rate-determining step of the overall hydride transfer reactions [16,87,149]. The Mg2+ ion has also been shown to accelerate electron transfer from cis-dialkylcobalt(III) complexes to p-ben-zoquinone derivatives [150,151]. In this context, a remarkable catalytic effect of Mg2+ was also found on photoinduced electron transfer reactions from various electron donors to flavin analogs in 1984 [152], The Mg2+ (or Zn2+) ion forms complexes with a flavin analog la and 5-deazaflavins 2a-c with a 1 1 stoichiometry in dry MeCN at 298 K [153] ... 

HYDRIDE-TRANSFER REACTIONS INVOLVING NICOTINAMIDE COFACTORS... 

Mixed labeling experiments with specifically isotopically substituted 4R- and 4S-NADPH cofactors established the primary and secondary kinetic isotope effects and their temperature dependence for the hydride transfer reaction. Indeed, resulting data could be rationalized only by a reaction model featuring an extensive tunneling contribution that is environmentally coupled. The difference in the observed and calculated intrinsic kinetic isotope effects requires a commitment factor arising from dissecting the pre-steady state hydride step into kinetic steps, one the actual hydride transfer step itself and the other a motion of the protein and/or nicotinamide associated with the hydride transfer step [17]. 

Nature makes use of NADH (reduced nicotinamide adenine dinucleotide) as a cofactor for enantioselective biochemical hydrogenations, which are typical hydride-transfer reactions. Dihydropyridines and benzimidazolines derivatives are active hydride donors due to the presence of the nitrogen atom and the ability of the molecule to undergo aromatisation. Organocatalytic enantioselective reductions carried out using hydride donors has been studied, and effective reductions have been achieved with imidazoli-dinone organocatalysts, both with a,p unsaturated aldehydes and ketones. Generally, a stoichiometric quantity of reductant (Hantzsch ester 4) is required for these transformations (Scheme 18.5). 

Isotope effects have been used to determine whether the hydride transfer from the enzyme cofactor nicotinamide-adenine dinucleotide (NADH) (reaction (43)) takes place as a hydride ion transfer in a single kinetic step or in a multistep reaction via an uncoupled electron and hydrogen transfer. 

Pyridoxal-5 -Phosphate Is Required for a Variety of Reactions with a-Amino Acids Nicotinamide Coenzymes Are Used in Reactions Involving Hydride Transfers Flavins Arq Used in Reactions Involving One or Two Electron Transfers... 

Nicotinamide Coenzymes Are Used in Reactions Involving Hydride Transfers... 

Alcohol oxidation requires release of a proton, which formally comes from the alcohol. In other dehydrogenases such as lactate dehydrogenase, proton release occurs simultaneously with hydride transfer. In liver ADH proton release can be demonstrated, by reaction of the proton with an indicator such as thymol blue or phenol red in stopped-flow spectrophotometry, to be faster than hydride transfer, 270 vs. 150 s and unaffected by use of deuterated substrate, so it occurs before hydride transfer. Binding of the NAD+ nicotinamide ring is accompanied by a conformational change of ADH bringing the catalytic zinc about 0.1 nm closer to the... 

Trichloromethylarenes are found to activate the pyridine ring via N-alkylation such that 4-chloropyridines are formed (Scheme 20) <1995TL5075>. In the case of nicotinamide, the dihydropyridine intermediate 121 undergoes an intermolecular redox reaction with hydride transferred to the benzylic position to give 122. Subsequent displacement of the C-4 chloride with nicotinamide affords the bispyridinium salts 123. 

Nicotinamide adenine dinucleotide is a coenzyme which is only loosely bound to the active site of the enzymes with which it interacts and is free therefore, to dissociate from the enzyme during the catalytic cycle. The role of the dehydrogenase enzyme is to bring together the substrate and the NAD+ in the correct orientation for the two to react. These NAD+-dependent enzymes are known as dehydrogenases. They work in conjunction with NAD+ to oxidise substrates by the transfer of 1H+ and 2e from the substrate to the 4-position of the nicotinamide ring of the NAD+ (see Fig. 2.1). The overall reaction is the equivalent of a hydride transfer and is commonly referred to as such. NAD+-dependent enzymes are primarily involved in respiration (NAD+ occurs in significant amounts in mitochondria), whereas, NADP+-dependent coenzymes are primarily involved in the transfer of electrons from intermediates in catabolism. 

There are a considerable number of reactions in which the products contain two electrons, more than the starting compounds, and the consecutive two-step one-electron electron transfer process proves to be energetically unfavorable. In such cases, it is presumed that the two-electron process occurs in one elementary two-electron step. An example of a two-electron process is the hydride transfer, when two electrons are transported together with a proton. BH4, hydroquinones and reduced nicotinamides are typical hydrid donors. A specific feature of quinones is the capacity to accept and then to reversibly release electrons one by one or two electrons as a hydride. Therefore, quinones can serve as a molecular device, which can switch consecutive one-electron process to single two-electron process. 

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