Applications of deuterium isotope effects for probing aspects of reactions involving oxidative addition and reductive elimination of H–H and C–H bonds

Parkin, Gerard

doi:10.1002/jlcr.1435

Cited by 42 publications

(36 citation statements)

References 102 publications

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“…32,33 The inverse kinetic isotope effect could correspond to a late transition state for H-H bond formation in which the high-frequency H-H bond is mostly formed, or could reflect an equilibrium with a transient H 2 complex. 34 The kinetics do not show whether the hydrides in the intermediate are connected to one or both iron atoms.…”

Section: Resultsmentioning

confidence: 98%

The Mechanism of N–N Double Bond Cleavage by an Iron(II) Hydride Complex

et al. 2016

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The use of hydride species for substrate reductions avoids strong reductants, and may enable nitrogenase to reduce multiple bonds without unreasonably low redox potentials. In this work, we explore the N=N bond cleaving ability of a high-spin iron(II) hydride dimer with concomitant release of H2. Specifically, this diiron(II) reacts with azobenzene (PhN=NPh) to perform the four-electron reduction to two imido groups, where two electrons come from H2 reductive elimination and the other two come from iron oxidation. The rate law of the H2 releasing reaction indicates that diazene binding occurs prior to H2 elimination, and the negative entropy of activation and inverse kinetic isotope effect indicate that H-H bond formation is the rate-limiting step. Thus, substrate binding causes reductive elimination of H2 that formally reduces the metals, and the metals use the additional two electrons to cleave the N-N multiple bond.

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Section: Resultsmentioning

confidence: 98%

The Mechanism of N–N Double Bond Cleavage by an Iron(II) Hydride Complex

et al. 2016

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“…KIE experiments are often designed and employed to support a computational hypothesis. Thus a change in the reaction rate following replacement of an atom (typically hydrogen) by its isotope (deuterium) can be compared with the theoretical KIE values to provide essential experimental information on the calculated mechanistic pathway …”

Section: Applications Of Deuterium‐labelled Compoundsmentioning

confidence: 99%

“…[25] KIE experiments are often designed and employed to support ac omputational hypothesis.T hus ac hange in the reaction rate following replacement of an atom (typically hydrogen) by its isotope (deuterium) can be compared with the theoretical KIE values to provide essential experimental information on the calculated mechanistic pathway. [26] Three different experimental designs are typically used (Scheme 3). 1) KIEs determined from the absolute rates of two parallel reactions;2)KIEs determined from an intermolecular competition between deuterium-labelled and unlabelled substrate in the same reaction flask;a nd 3) KIEs determined from an intramolecular competition, for example, by placing adirecting group (DG) between the C À Hand C À D bonds.A part from differences in feasibility and precision, these different kinds of experiments may also differ in terms of the information that they provide.…”

Section: Isotope Effects For the Investigation Of Chemical Reaction Mmentioning

confidence: 99%

Deuterium‐ and Tritium‐Labelled Compounds: Applications in the Life Sciences

Atzrodt¹,

Derdau²,

et al. 2018

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Hydrogen isotopes are unique tools for identifying and understanding biological and chemical processes. Hydrogen isotope labelling allows for the traceless and direct incorporation of an additional mass or radioactive tag into an organic molecule with almost no changes in its chemical structure, physical properties, or biological activity. Using deuterium-labelled isotopologues to study the unique mass-spectrometric patterns generated from mixtures of biologically relevant molecules drastically simplifies analysis. Such methods are now providing unprecedented levels of insight in a wide and continuously growing range of applications in the life sciences and beyond. Tritium ( H), in particular, has seen an increase in utilization, especially in pharmaceutical drug discovery. The efforts and costs associated with the synthesis of labelled compounds are more than compensated for by the enhanced molecular sensitivity during analysis and the high reliability of the data obtained. In this Review, advances in the application of hydrogen isotopes in the life sciences are described.

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“…In one particularly active branch of such labelling research, hydrogen isotope exchange (HIE) is employed to deliver either deuterium or radioactive tritium to pharmaceutical drug candidates in one synthetic step. As well as circumventing the requirement for isotopically-enriched starting materials in preparing tritiated drug candidates [1,5], HIE can also provide analogous deuterated compounds for use as internal standards for mass spectrometry [11,12], for kinetic isotope studies [13,14], and for the alteration of reaction pathways in total synthesis [15].…”

Section: Introductionmentioning

confidence: 99%

Iridium-Catalysed ortho-Directed Deuterium Labelling of Aromatic Esters—An Experimental and Theoretical Study on Directing Group Chemoselectivity

et al. 2015

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Herein we report a combined experimental and theoretical study on the deuterium labelling of benzoate ester derivatives, utilizing our developed iridium N-heterocyclic carbene/phosphine catalysts. A range of benzoate esters were screened, including derivatives with electron-donating and -withdrawing groups in the para-position. The substrate scope, in terms of the alkoxy group, was studied and the nature of the catalyst counter-ion was shown to have a profound effect on the efficiency of isotope exchange. Finally, the observed chemoselectivity was rationalized by rate studies and theoretical calculations, and this insight was applied to the selective labelling of benzoate esters bearing a second directing group.

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Applications of deuterium isotope effects for probing aspects of reactions involving oxidative addition and reductive elimination of H–H and C–H bonds

Abstract: The various types of deuterium isotope effects that are observed for reactions involving oxidative addition and reductive elimination reactions of H-H and C-H bonds with a transition metal center are reviewed.

Cited by 42 publications

References 102 publications

The Mechanism of N–N Double Bond Cleavage by an Iron(II) Hydride Complex

The Mechanism of N–N Double Bond Cleavage by an Iron(II) Hydride Complex

Deuterium‐ and Tritium‐Labelled Compounds: Applications in the Life Sciences

Iridium-Catalysed ortho-Directed Deuterium Labelling of Aromatic Esters—An Experimental and Theoretical Study on Directing Group Chemoselectivity

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