Mechanisms of hydrogen transfer

Since the first use of catalyzed hydrogen transfer, speculations about, and studies on, the mechanism(s) involved have been extensively published. Especially in recent years, several investigations have been conducted to elucidate the reaction pathways, and with better analytical methods and computational chemistry the catalytic cycles of many systems have now been clarified. The mechanism of transfer hydrogenations depends on the metal used and on the substrate. Here, attention is focused on the mechanisms of hydrogen transfer reactions with the most frequently used catalysts. Two main mechanisms can be distinguished (i) a direct transfer mechanism by which a hydride is transferred directly from the donor to the acceptor molecule and (ii) an indirect mechanism by which the hydride is transferred from the donor to the acceptor molecule via a metal hydride intermediate (Scheme 20.3). 

Mechanism of Hydrogen Transfer by Pyridine Nucleotide Coenzymes 239... 

Wl. Wallenfels, K., Mechanism of hydrogen transfer with pyridine nucleotides. In Steric Course of Microbiological Reactions" (G. E. W. Wolstenholme and C. M. O Connor, eds.), pp. 10-36. J. A. Churchill, London, 1959. 

The transfer of hydrogen to the alkene also occurs by a radical process,55,50 and not by the insertion reaction which is much more common in homogeneous hydrogenation. These kinetic studies were carried out using cinnamic acid as alkene. The observation of alkenyl and allyl species in diene hydrogenation suggests that a different mechanism of hydrogen transfer may... 

Frey, P. A., Essenberg, M. K., and Abeles, R. H., 1967, Studies on the mechanism of hydrogen transfer in the cobamide coenzyme-dependent dioldehydrase reaction. J. Biol. Chem. 242 5369n5377. 

Durham, L. J., Larsson, A., and Reichard, P., 1967, Enzymatic synthesis of deoxyribonu-cleotides II. The mechanism of hydrogen transfer of the ribonucleoside diphosphate reductase system from Escherichia coli studied with nuclear magnetic resonance. European J. Biochem. I 92n95. 

Hydrides of tin and germanium also reduce quinones, ultimately to the hydroquinones. The detailed mechanism of hydrogen transfer between four stannanes and four quinones has been studied which suggested a radical mechanism in which hydrogen transfer was the first step. ... 

Studies on the role of a Ru catalyst as well as the mechanism of hydrogen transfer in enone reduction with benzyl alcohol at 170-190 °C revealed that RuCl2(PPh3)3 is converted by the primary alcohol into RuH2(CO)(PPh3)3, which then hydrogenates benzylideneacetone. ... 

Metal catalysis of olefin and arene hydrogenation is critically dependent on the reactive hydridometal intermediates. However, little is known about the mechanism of hydrogen transfer and hydrometallation and the reactive intermediates involved. The observation of transient charge-transfer absorption during hydrogenation and hydrometallation of olefins with tungsten or molybdenum hydrides [185], opens up the question of a possible electron-transfer mechanism in which the overall hydrogen-atom transfer is the result of a two-step electron-transfer-proton-transfer (ET-PT) process (Eq. 58). 

The dominant tool to study hydrogen tunneling in an enzyme reaction is the measurement of isotope effects on the chemical step of catalysis via steady-state kinetics experiments. However, steady-state kinetics are often complicated by the contribution of several microscopic steps to the macroscopically observed rates, making it difficult to study the chemical step. The following section introduces basic enzyme kinetics, with a discussion of the macroscopic rate constants kat and kcat/ M and their interpretations. More detailed references on this matter are available [1, 2]. The first concern of the experimentalist is to be able to observe the intrinsic rate of chemistry, thereby allowing probes into the mechanism of hydrogen transfer. 

Wallenfels K and Sund H, Mechanism of hydrogen transfer with pyridine nucleotides. III. Binary and ternary zinc complexes as models for enzyme-coenzyme bonds, Biochem. Z., 329, 41-47 (1957). 

Cronauer, D.C., D.M, Jewell, Y.T. Shah and R.J, Modi, "Investigation of Mechanisms of Hydrogen Transfer in Coal Hydrogenation." Phase I final report under DOE Contract No. E(49-18)-2305 (February, 1978). 

Fig. 59. The mechanism of hydrogen transfer from 2-propanol to cycloalkenes by the RhH(PPhs)4 complex.

Nicotinamide functions in the animal body as the active group of two important coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP).These coenzymes are involved in the mechanism of hydrogen transfer in living cells (see Chapter 9) NAD is involved in the oxidative phosphorylation system, the tricyclic acid (TCA) cycle and the metabolism of many molecules, including pyruvate, acetate, (3-hydroxy-butyrate, glycerol, fatty acids and glutamate NADPH is the hydrogen acceptor in the pentose phosphate pathway. 

The mechanism of hydrogen transfer in enzymatic transamination has been studied by Konikova, Kritzmann and Teiss (102) ine xperiments with a deuterio-alanine. In the presence of crude gl-aph and of KG the greater part of the deuterium contained in labeled AL passes into the water the newly formed GL contains practically no excess of D. No significant loss of... 

The mechanism of hydrogen transfer to ketones, catalysed by Knolker s iron complex (29) (TMS = trimethylsilyl), has been studied by applying DFT calculations to a semi-simplified system for two inner-sphere mechanisms and three outer-sphere mechanisms. An outer-sphere mechanism involving a concerted hydrogen transfer to the substrate is found to be the most kinetically feasible. The real system had a higher free energy barrier because of the steric effect of the substituent group. 

There is no definite knowledge of the mechanism of hydrogen transfer in the diamine oxidase system. Zeller et al. 170) postulate that the reaction involves a transfer of the hydrogen from the substrate to an acceptor on diamine oxidase followed by the transfer of this hydrogen to molecular oxygen under the influence of a second enzyme. 

The mechanism of hydrogen transfer by coenzyme B12 seems to be clear. This is not the state of affairs as regards the nature of the other group which undergoes transfer. A number of different intermediates... 

Finally, preliminary experiments show that cinnamaldehyde can be photocatalytically hydrogenated into cinnamyl alcohol by a mechanism of hydrogen transfer from an alcohol, via a bronze HxMo03, to cinnamaldehyde. Under the same conditions, Pt/Ti02, used as a reference bifunctional photocatalyst, leads to the saturation of the C=C bond. 

Hemmerich, P., and M. Schuman-Jorns Mechanisms of Hydrogen Transfer in Redox Enzymes. In Enzymes Structure and Function (J. Drenth, R. A. Oosterbaan, C. Veeger, eds.), p. 95. Amsterdam North Holland Pub. Corp. 1972. 

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