Proton and Hydride Transfer Reactions

Ab initio quantum mechanical methods are needed to semi quantitatively study chemical reactions involving bond breaking and bond forming phenomena. Once a reaction path for a chemical process is defined, it is possible to obtain the key transition geometries and associated energies of 

The functional form of Emm is the same as in Galaxy and AMBER (version 3.331). The form of EMm is described as, 

The free energy profile of the enzymatic reaction is decomposed into two components as, 

The statistical perturbation theory arising from the classical work of Zwanzig34 and its detailed implementation in a molecular dynamics program for computation of free energies is described in detail elsewhere.35 36 We give a very brief description of the method for the sake of completeness. The total Hamiltonian of a system may be written as the sum of the Hamiltonian (Ho) of the unperturbed system and the perturbation (Hi)  

In the above equation, HA is the Hamiltonian for the system at state A, and Hb is that for state B. The above equation implies that, when X = 1, H = Ha i.e., the system is purely in state A and when X = 0, H = HB at which 

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ELECTROCATALYTIC REDUCTION OF PROTONS AND HYDRIDE TRANSFER REACTIONS... 

The proposed mechanism shown in Scheme 7.11 is supported by stoichiometric proton- and hydride-transfer reactions of metal hydrides that were dis-... 

Recently, a controversial debate has arisen about whether the optimization of enzyme catalysis may entail the evolutionary implementation of chemical strategies that increase the probability of tunneling and thereby accelerate reaction rates [7]. Kinetic isotope effect experiments have indicated that hydrogen tunneling plays an important role in many proton and hydride transfer reactions in enzymes [8, 9]. Enzyme catalysis of horse liver alcohol dehydrogenase may be understood by a model of vibrationally enhanced proton transfer tunneling [10]. Furthermore, the double proton transfer reaction in DNA base pairs has been studied in detail and even been hypothesized as a possible source of spontaneous mutation [11-13]. 

Figure 7. Proton- and hydride-transfer reactions connecting alcohols and carbonyl compounds.

Stage 1 is the calculation of the PMF along the distingished reaction coordinate and various types of reaction coordinates can be used, for example, proton and hydride transfer reactions could be evaluated with a geometry-based distinguished reaction coordinate described by the difference between the breaking and forming bond distances as... 

Molybdenum and tungsten carbonyl hydride complexes were shown (Eqs. (16), (17), (22), (23), (24) see Schemes 7.5 and 7.7) to function as hydride donors in the presence of acids. Tungsten dihydrides are capable of carrying out stoichiometric ionic hydrogenation of aldehydes and ketones (Eq. (28)). These stoichiometric reactions provided evidence that the proton and hydride transfer steps necessary for a catalytic cycle were viable, but closing of the cycle requires that the metal hydride bonds be regenerated from reaction with H2. 

The mechanism of the Meerwein-Pondorf-Verley reaction is by coordination of a Lewis acid to isopropanol and the substrate ketone, followed by intermolecular hydride transfer, by beta elimination [41]. Initially, the mechanism of catalytic asymmetric transfer hydrogenation was thought to follow a similar course. Indeed, Backvall et al. have proposed this with the Shvo catalyst [42], though Casey et al. found evidence for a non-metal-activation of the carbonyl (i.e., concerted proton and hydride transfer [43]). This follows a similar mechanism to that proposed by Noyori [44] and Andersson [45], for the ruthenium arene-based catalysts. By the use of deuterium-labeling studies, Backvall has shown that different catalysts seem to be involved in different reaction mechanisms [46]. 

For this reaction the transition state drawn in Equation 11.82 involving simultaneous proton and hydride transfers has been proposed to explain the observed isotope effects. 

Figure 10.9 shows the orbital interactions for typical hydrogen atom transfer reaction. It is in fact the same diagram that described proton and hydride transfers (Figures 10.1 and... 

Enthalpies of activation, transition-state geometries, and primary semi-classical (without tunneling) kinetic isotope effects (KIEs) have been calculated for 11 bimolecu-lar identity proton-transfer reactions, four intramolecular proton transfers, four nonidentity proton-transfer reactions, 11 identity hydride transfers, and two 1,2-intramole-cular hydride shifts at the HF/6-311+G, MP2/6-311+G, and B3LYP/6-311+-1-G levels.134 It has been found that the KIEs are systematically smaller for hydride transfers than for proton transfers. The differences between proton and hydride transfers have been rationalized by modeling the central C H- C- unit of a proton-transfer transition state as a four-electron, three-centre (4-e 3-c) system and the same unit of a hydride-transfer transition state as a 2-e 3-c system. 

Tapia, O., Andres, J., Moliner, V. and Stamato, F. L. M. G. (1997) Theory of solvent effects and the description of chemical reactions. Proton and hydride transfer processes, in Hadzi, D. (edr), Theoretical treatments of hydrogen bonding, John Wiley and Sons, New York, pp. 143-164,... 

Lactate dehydrogenase is a pyridine nucleotide oxidoreductase, a tetramer of 140 kD molecular weight, which has been extensively investigated (Bloxham et al., 1975 Eventoff et al., 1977). It catalyses the reversible oxidation of L-lactate to pyruvate using NAD+ as a coenzyme. The reaction scheme with a view of the active site with bound substrate and essential amino-acid side chains are depicted in Equation (3) and in Figure 17. The probable reaction mechanism, involving proton and hydride transfers,... 

Oligomerization of olefins and their homologation by methanol (or methanol -derived species) appear to be essential features of methanol conversion over ZSM-5 zeolite. A self-consistent-interpretation of the entire process is possible in terms of Rr nsted-acid ZSM-5 zeolite catalysing proton transfer and methylation reactions, and the formation of carbenium ions, and their various oligomerization, cracking, rearrangement and hydride-transfer reactions. 

Proton-Coupled Electron Transfer in Hydrogen and Hydride Transfer Reactions... 

As demonstrated in this chapter, there have always been the fundamental mechanistic questions in oxidation of C-H bonds whether the rate-determining step is ET, PCET, one-step HAT, or one-step hydride transfer. When the ET step is thermodynamically feasible, ET occurs first, followed by proton transfer for the overall HAT reactions, and the HAT step is followed by subsequent rapid ET for the overall hydride transfer reactions. In such a case, ET products, that is, radical cations of electron donors and radical anions of electron acceptors, can be detected as the intermediates in the overall HAT and hydride transfer reactions. The ET process can be coupled by proton transfer and also by hydrogen bonding or by binding of metal ions to the radical anions produced by ET to control the ET process. The borderline between a sequential PCET pathway and a one-step HAT pathway has been related to the borderline between the outer-sphere and inner-sphere ET pathways. In HAT reactions, the proton is provided by radical cations of electron donors because the acidity is significantly enhanced by the one-electron oxidation of electron donors. An electron and a proton are transferred by a one-step pathway or a sequential pathway depending on the types of electron donors and acceptors. When proton is provided externally, ET from an electron donor that has no proton to be transferred to an electron acceptor (A) is coupled with protonation of A -, when the one-electron reduction and protonation of A occur simultaneously. The mechanistic discussion described in this chapter will provide useful guide to control oxidation of C-H bonds. 

There is rapid interconversion of alkenes and carbocations over acidic zeolite catalysts, and the carbocations permit skeletal rearrangements and hydride transfer reactions. These reactions proceed in the direction of formation of more stable isomers. The rearrangements probably proceed through protonated cyclopropanes (see Section 4.4.4). 

Studies of the kinetics and thermodynamics of proton transfer and hydride transfer reactions have led to a better fundamental understanding of the range of reactivity available, and how it is influenced by different metals and ligands. This information is also central to the rational development of molecular catalysts for oxidation of H2 and production of H2 described in Chapter 7, and in the broad context of other reactions pertinent to energy production and energy utilization that require control of multi-proton and multi-electron reactivity. 

Hutchings, M. G., Gasteiger, J. A Quantitative Description of Fundamental Polar Reaction TVpes. Proton- and Hydride-Transfer factions Connecting Alcohols and Carbonyl Compounds in the Gas Phase . J. Chem. Soc. Perkin Trans. 2,1986, 447-454. 

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