Mechanism of Reduction of an Aminyl Radical Intermediate in the Radical SAM GTP 3′,8-Cyclase MoaA

Here, we report an exquisite strategy that the B12 enzymes exploit to manipulate the reactivity of their radical intermediate (Adenosyl radical). Based on the quantum-mechanic calculations, these enzymes utilize a little known long-ranged through space quantum Coulombic effect (QCE). The QCE causes the radical to acquire an electronic structure that contradicts the Aufbau Principle: The singly-occupied molecular orbital (SOMO) is no longer the highest-occupied molecular orbital (HOMO) and the radical is unable to react with neighbouring substrates. The dynamic nature of the enzyme and its structure is expected to be such that the reactivity of the radical is not restored until it is moved into close proximity of the target substrate. We found that the hydrogen bonding interaction between the nearby conserved glutamate residue and the ribose ring of Adenosyl radical plays a crucial role in manipulating the orbital ordering

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Radical Enzymes Control the Chemistry of Their Highly Reactive Intermediates Using the Quantum Coulombic Effect

10.26434/chemrxiv.12839177 ◽

2020 ◽

Author(s):

Hossein Khalilian ◽

Gino A. DiLabio

Keyword(s):

Hydrogen Bonding ◽

Molecular Orbital ◽

Reactive Intermediates ◽

Hydrogen Bonding Interaction ◽

Orbital Ordering ◽

Dynamic Nature ◽

Radical Intermediate ◽

Highest Occupied Molecular Orbital ◽

Bonding Interaction ◽

Close Proximity

Here, we report an exquisite strategy that the B12 enzymes exploit to manipulate the reactivity of their radical intermediate (Adenosyl radical). Based on the quantum-mechanic calculations, these enzymes utilize a little known long-ranged through space quantum Coulombic effect (QCE). The QCE causes the radical to acquire an electronic structure that contradicts the Aufbau Principle: The singly-occupied molecular orbital (SOMO) is no longer the highest-occupied molecular orbital (HOMO) and the radical is unable to react with neighbouring substrates. The dynamic nature of the enzyme and its structure is expected to be such that the reactivity of the radical is not restored until it is moved into close proximity of the target substrate. We found that the hydrogen bonding interaction between the nearby conserved glutamate residue and the ribose ring of Adenosyl radical plays a crucial role in manipulating the orbital ordering

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A Reinvestigation of the Deceptively Simple Reaction of Toluene with ●OH, and the Fate of the Benzyl Radical. I. a Combined Thermodynamic and Kinetic Study on the Competition Between ●OH Addition and Hydrogen Abstraction Reactions.

10.26434/chemrxiv.8281283.v1 ◽

2019 ◽

Author(s):

Zoi Salta ◽

Agnie M. Kosmas ◽

Marc E. Segovia ◽

Martina Kieninger ◽

Oscar Ventura ◽

...

Keyword(s):

Density Functional ◽

Room Temperature ◽

Hydrogen Abstraction ◽

Reaction Rates ◽

Composite Model ◽

Alternative Mechanism ◽

Radical Intermediate ◽

Experimental Conditions ◽

Methyl Group ◽

Benzyl Radical

This work reports density functional and composite model chemistry calculations performed on the reactions of toluene with the hydroxyl radical. Both experimentally observed H-abstraction from the methyl group and possible additions to the phenyl ring were investigated. Reaction enthalpies and heights of the barriers suggest that H-abstraction is more favorable than ●OH addition to the ring. The calculated reaction rates at room temperature and the radical-intermediate product fractions support this view. This is somehow contradictory with the fact that, under most experimental conditions, cresols are observed in a larger concentration than benzaldehyde. Since the accepted mechanism for benzaldehyde formation involves H-abstraction, a contradiction arises that begs for an explanation. In this first part of our work we give the evidences that support the preference of hydrogen abstraction over ●OH addition and suggest an alternative mechanism which shows that cresols can actually arise also from the former reaction and not only from the latter.

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A Reinvestigation of the Deceptively Simple Reaction of Toluene with ●OH, and the Fate of the Benzyl Radical. I. a Combined Thermodynamic and Kinetic Study on the Competition Between ●OH Addition and Hydrogen Abstraction Reactions.

10.26434/chemrxiv.8281283 ◽

2019 ◽

Author(s):

Zoi Salta ◽

Agnie M. Kosmas ◽

Marc E. Segovia ◽

Martina Kieninger ◽

Oscar Ventura ◽

...

Keyword(s):

Density Functional ◽

Room Temperature ◽

Hydrogen Abstraction ◽

Reaction Rates ◽

Composite Model ◽

Alternative Mechanism ◽

Radical Intermediate ◽

Experimental Conditions ◽

Methyl Group ◽

Benzyl Radical

This work reports density functional and composite model chemistry calculations performed on the reactions of toluene with the hydroxyl radical. Both experimentally observed H-abstraction from the methyl group and possible additions to the phenyl ring were investigated. Reaction enthalpies and heights of the barriers suggest that H-abstraction is more favorable than ●OH addition to the ring. The calculated reaction rates at room temperature and the radical-intermediate product fractions support this view. This is somehow contradictory with the fact that, under most experimental conditions, cresols are observed in a larger concentration than benzaldehyde. Since the accepted mechanism for benzaldehyde formation involves H-abstraction, a contradiction arises that begs for an explanation. In this first part of our work we give the evidences that support the preference of hydrogen abstraction over ●OH addition and suggest an alternative mechanism which shows that cresols can actually arise also from the former reaction and not only from the latter.

Download Full-text