Mechanisms and energetics for N-glycosidic bond cleavage of protonated adenine nucleosides: N3 protonation induces base rotation and enhances N-glycosidic bond stability

2016 ◽  
Vol 18 (23) ◽  
pp. 16021-16032 ◽  
Author(s):  
R. R. Wu ◽  
M. T. Rodgers
Keyword(s):  
Hydrogen Bonding ◽  
Bond Cleavage ◽  
Glycosidic Bond ◽  
Hydrogen Bonding Interaction ◽  
Bond Stability ◽  
Bonding Interaction ◽  
Glycosidic Bond Cleavage ◽  
Glycosidic Bond Stability

N3 protonation induces base rotation and stabilizes the syn orientation of the adenine nucleobase of [dAdo+H]+ and [Ado+H]+via formation of a strong intramolecular N3H+⋯O5′ hydrogen-bonding interaction, which in turn influences the mechanisms and energetics for N-glycosidic bond cleavage.

Mechanisms and energetics for N-glycosidic bond cleavage of protonated 2′-deoxyguanosine and guanosine

2016 ◽  
Vol 18 (4) ◽  
pp. 2968-2980 ◽  
Author(s):  
R. R. Wu ◽  
Yu Chen ◽  
M. T. Rodgers
Keyword(s):  
Bond Cleavage ◽  
Glycosidic Bond ◽  
Bond Stability ◽  
Glycosidic Bond Cleavage ◽  
Glycosidic Bond Stability

TCID thresholds of [dGuo/Guo+H]+ indicate that 2′-hydroxyl strengthens glycosidic bond stability but slightly weakens the competition between the two primary dissociation pathways of [Guo+H]+vs. [dGuo+H]+.

Glycosidic bond cleavage in deoxynucleotides — A density functional study

2009 ◽  
Vol 87 (7) ◽  
pp. 850-863 ◽  
Author(s):  
Andrea L. Millen ◽  
Stacey D. Wetmore
Keyword(s):  
Hydrogen Bonding ◽  
Density Functional ◽  
Bond Cleavage ◽  
High Energy ◽  
Glycosidic Bond ◽  
Functional Study ◽  
Purine Nucleotides ◽  
Aqueous Environments ◽  
Glycosidic Bond Cleavage ◽  
Reaction Energies

Density functional theory was used to study the glycosidic bond cleavage in deoxynucleotides with the main goal to determine the effects of the nucleobase, hydrogen bonding with the nucleobase, and the (bulk) environment on the reaction energetics. Since direct glycosidic bond cleavage is a high-energy process, two nucleophile models were considered (HCOO–···H2O and HO–), which represent different stages of activation of a water nucleophile. The glycosidic bond cleavage barriers were found to decrease, while the reaction exothermicity increases, with an increase in the nucleobase acidity. The gas-phase barriers and reaction energies for bond cleavage in all deoxynucleotides were found to be significantly affected by hydrogen-bonding interactions with the nucleobase (by up to 30 kJ mol–1 depending on the nucleophile). Although the barriers increase and reaction energies become less exothermic in enzymatic and aqueous environments, the effects of the bulk environment are similar in the presence and absence of small molecules bound to the nucleobase. Therefore, the effects of hydrogen bonding with the bases are approximately the same in all environments. Our results suggest that hydrogen bonding with the nucleobase may play an important role in the glycosidic bond cleavage in both pyrimidine and purine nucleotides in a variety of environments.

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

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

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

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

Sign in / Sign up

Export Citation Format

Share Document