Quaternary Charge-Transfer Complex Enables Photoenzymatic In-termolecular Hydroalkylation of Olefins

Intermolecular C–C bond-forming reactions are underdeveloped transformations in the field of biocatalysis. Here we report a photoenzymatic intermolecular hydroalkylation of olefins catalyzed by flavin-dependent ‘ene’reductases. Radical initiation occurs via photoexcitation of a rare high-order enzyme-templated charge-transfer complex that forms between an alkene, 𝛼-chloroamide, and flavin hydroquinone. This unique mechanism ensures that radical formation only occurs when both substrates are present within the protein active site. This active site can control the radical terminating hydrogen atom transfer, enabling the synthesis of enantioenriched γ-stereogenic amides. This work highlights the potential for photoenzymatic catalysis to enable new biocatalytic transformations via previously unknown electron transfer mechanisms.

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Atmospheric formation of the NO3 radical from gas-phase reaction of HNO3 acid with the NH2 radical: proton-coupled electron-transfer versus hydrogen atom transfer mechanisms

Physical Chemistry Chemical Physics ◽

10.1039/c4cp02792b ◽

2014 ◽

Vol 16 (36) ◽

pp. 19437-19445 ◽

Cited By ~ 13

Author(s):

Josep M. Anglada ◽

Santiago Olivella ◽

Albert Solé

Keyword(s):

Electron Transfer ◽

Hydrogen Atom ◽

Hydrogen Atom Transfer ◽

Atom Transfer ◽

Phase Reaction ◽

Electron Transfer Mechanism ◽

Proton Coupled Electron Transfer ◽

No3 Radical ◽

Transfer Mechanisms ◽

Atmospheric Formation

The amidogen radical abstracts the hydrogen from nitric acid through a proton coupled electron transfer mechanism rather than by an hydrogen atom transfer process.

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DFT study of free radical scavenging activity of erodiol

Chemical Papers ◽

10.2478/s11696-013-0402-0 ◽

2013 ◽

Vol 67 (11) ◽

Cited By ~ 7

Author(s):

Zoran Marković ◽

Jelena Đorović ◽

Milan Dekić ◽

Milanka Radulović ◽

Svetlana Marković ◽

...

Keyword(s):

Electron Transfer ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Hydrogen Atom Transfer ◽

Free Radical Scavenging ◽

Single Electron Transfer ◽

Transfer Energy ◽

Dissociation Enthalpy ◽

Proton Dissociation ◽

Transfer Mechanisms

AbstractAntioxidant activity of erodiol was examined at the M05-2X/6-311+G(d,p) level of theory in the gas and aqueous phases. The structure and energy of radicals and anions of the most stable erodiol rotamer were analyzed. To estimate antioxidant potential of erodiol, different molecular properties were examined: bond dissociation enthalpy, proton affinity together with electron transfer energy, and ionization potential followed by proton dissociation enthalpy. It was found that hydrogen atom transfer is the prevailing mechanism of erodiol behavior in gas; whereas single electron transfer followed by proton transfer and sequential proton loss electron transfer mechanisms represent the thermodynamically preferred reaction paths in water.

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Radical Biocatalysis: Using Non-Natural Single Electron Transfer Mechanisms to Access New Enzymatic Functions

Synlett ◽

10.1055/s-0037-1611818 ◽

2019 ◽

Vol 31 (03) ◽

pp. 248-254 ◽

Cited By ~ 4

Author(s):

Todd K. Hyster

Keyword(s):

Electron Transfer ◽

Active Sites ◽

Hydrogen Atom Transfer ◽

Single Electron ◽

Great Promise ◽

Single Electron Transfer ◽

Radical Intermediates ◽

Redox Activation ◽

Transfer Mechanisms ◽

Ground State Electron

Exploiting non-natural reaction mechanisms within native enzymes is an emerging strategy for expanding the synthetic capabilities of biocatalysts. When coupled with modern protein engineering techniques, this approach holds great promise for biocatalysis to address long-standing selectivity and reactivity challenges in chemical synthesis. Controlling the stereochemical outcome of reactions involving radical intermediates, for instance, could benefit from biocatalytic solutions because these reactions are often difficult to control by using existing small molecule catalysts. General strategies for catalyzing non-natural radical reactions within enzyme active sites are, however, undeveloped. In this account, we highlight three distinct strategies developed in our group that exploit non-natural single electron transfer mechanisms to unveil previously unknown radical biocatalytic functions. These strategies allow common oxidoreductases to be used to address the enduring synthetic challenge of asymmetric hydrogen atom transfer.1 Introduction2 Photoinduced Electron Transfer from NADPH3 Ground State Electron Transfer from Flavin Hydroquinone4 Enzymatic Redox Activation in NADPH-Dependent Oxidoreductases5 Conclusion

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Zur Theorie der Elektronenübergangsreaktionen in molekularen Komplexen / Theory of Electron Transfer Reactions in Molecular Complexes

Zeitschrift für Naturforschung A ◽

10.1515/zna-1974-0607 ◽

1974 ◽

Vol 29 (6) ◽

pp. 880-887 ◽

Cited By ~ 4

Author(s):

P. P. Schmidt

Keyword(s):

Activation Energy ◽

Electron Transfer ◽

Charge Transfer ◽

Rate Constant ◽

Reaction Rate ◽

Charge Transfer Complex ◽

Rate Theory ◽

Transfer Step ◽

Donor And Acceptor ◽

Inner Sphere

This paper reports a theory of the inner sphere-type electron transfer reaction. Inner sphere reactions, as opposed to the outer sphere variety, require that the solvate or ligand shells surrounding the electron donor and acceptor species undergo considerable change in the course of the electron transfer. In this paper we assume that the electron transfer step takes place in a molecular complex which exists in equilibrium with the reactants. The electron transfer step occurs as a non-radiative charge transfer-type transition. In this manner we treat the charge transfer kinetics, in particular, the evaluation of the reaction rate constant, in the same manner as is usual for non-radiative problems. The analysis leading to the rate constant expression is based on Yamamoto’s general chemical reaction rate theory. The rate constant expressions obtained are quite general, they hold for any degree of strength of coupling between subsystems comprising the entire system. The activation energy, in the Arrhenius form for the rate constant, shows a dependence on the energy (work) of formation of the intermediate charge transfer complex, on vibrational shift energies associated with the molecular motions of the ligands, and on solvent repolarization energies. The activation energy also shows an important dependence on coupling terms which link the vibrations of the molecular inner shell with the polarization states of the (assumed) dielectric continuum which surrounds the charge transfer participants. The approach we take in developing this theory we believe points the way towards the development of a more complete theory capable of accounting for the dynamics of the molecular reorganization leading to the intermediate charge transfer complex as well as accounting for the electron transfer step itself.

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Influence of polarity of medium on the nature of charge transfer complex, kinetics, and mechanism of reaction with a one-electron transfer in a tetracyanoethylene-n-alkyl-substituted aniline system

Theoretical and Experimental Chemistry ◽

10.1007/bf01135004 ◽

1989 ◽

Vol 25 (2) ◽

pp. 152-157

Author(s):

V. S. Kuts ◽

S. A. Biskulova

Keyword(s):

Electron Transfer ◽

Charge Transfer ◽

Charge Transfer Complex ◽

Kinetics And Mechanism ◽

Mechanism Of Reaction

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Uncovering alternate charge transfer mechanisms in Escherichia coli chemically functionalized with conjugated oligoelectrolytes

Chemical Communications ◽

10.1039/c4cc02784a ◽

2014 ◽

Vol 50 (60) ◽

pp. 8223-8226 ◽

Cited By ~ 29

Author(s):

Victor Bochuan Wang ◽

Natalia Yantara ◽

Teck Ming Koh ◽

Staffan Kjelleberg ◽

Qichun Zhang ◽

...

Keyword(s):

Escherichia Coli ◽

Electron Transfer ◽

Charge Transfer ◽

Extracellular Electron Transfer ◽

Transfer Mechanisms

Conjugated oligoelectrolytes integrated in Escherichia coli have been proposed to induce release of electroactive cytosolic components, which contributes to extracellular electron transfer.

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Role of active site conformational changes in photocycle activation of the AppA BLUF photoreceptor

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1621393114 ◽

2017 ◽

Vol 114 (7) ◽

pp. 1480-1485 ◽

Cited By ~ 17

Author(s):

Puja Goyal ◽

Sharon Hammes-Schiffer

Keyword(s):

Electron Transfer ◽

Free Energy ◽

Excited State ◽

Charge Transfer ◽

Conformational Changes ◽

Ground State ◽

Active Site ◽

Locally Excited ◽

Proton Relay ◽

Locally Excited State

Blue light using flavin adenine dinucleotide (BLUF) proteins are essential for the light regulation of a variety of physiologically important processes and serve as a prototype for photoinduced proton-coupled electron transfer (PCET). Free-energy simulations elucidate the active site conformations in the AppA (activation of photopigment and puc expression) BLUF domain before and following photoexcitation. The free-energy profile for interconversion between conformations with either Trp104 or Met106 closer to the flavin, denoted Trpin/Metout and Trpout/Metin, reveals that both conformations are sampled on the ground state, with the former thermodynamically favorable by ∼3 kcal/mol. These results are consistent with the experimental observation of both conformations. To analyze the proton relay from Tyr21 to the flavin via Gln63, the free-energy profiles for Gln63 rotation were calculated on the ground state, the locally excited state of the flavin, and the charge-transfer state associated with electron transfer from Tyr21 to the flavin. For the Trpin/Metout conformation, the hydrogen-bonding pattern conducive to the proton relay is not thermodynamically favorable on the ground state but becomes more favorable, corresponding to approximately half of the configurations sampled, on the locally excited state. The calculated energy gaps between the locally excited and charge-transfer states suggest that electron transfer from Tyr21 to the flavin is more facile for configurations conducive to proton transfer. When the active site conformation is not conducive to PCET from Tyr21, Trp104 can directly compete with Tyr21 for electron transfer to the flavin through a nonproductive pathway, impeding the signaling efficiency.

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