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| 2. |
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| 3. |
- Grand, André, et al.
(författare)
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*H and *OH radical reactions with 5-methylcytosine
- 2007
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Ingår i: Journal of Physical Chemistry A. - Washington, D.C. : American Chemical Society. - 1089-5639 .- 1520-5215. ; 111:37, s. 8968-8972
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Labet, Vanessa, et al.
(författare)
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Deamination of the radical cation of the base moiety of 2’deoxycytidine : A theoretical study
- 2008
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Ingår i: ChemPhysChem. - Weinheim : Wiley-VCH. - 1439-4235 .- 1439-7641. ; 9:8, s. 1195-1203
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Tidskriftsartikel (refereegranskat)abstract
- Five pathways leading to the deamination of cytosine (to uracil) after formation of its deprotonated radical cation are investigated in the gas phase, at the UB3LYP/6-311GACHTUNGTRENUNG(d,p) level of theory, and in bulk aqueous solvent. The most favorable pathway involves hydrogen-atom transfer from a water molecule to the N3 nitrogen of the deprotonated radical cation, followed by addition of the resulting hydroxyl radical to the C4 carbon of the cytosine derivative. Following protonation of the amino group (N4), the C4 N4 bond is broken with elimination of the NH3 ·+ radical and formation of a protonated uracil. The rate-determining step of this mechanism is hydrogen-atom transfer from a water molecule to the cytosine derivative. The associated free energy barrier is 70.2 kJmol 1.
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| 5. |
- Labet, Vanessa, et al.
(författare)
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Hydrolytic Deamination of 5,6-Dihydrocytosine in a Protic Medium : A Theoretical Study
- 2010
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Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 114:4, s. 1826-1834
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism for the deamination reaction of 5,6-dihydrocytosine with H2O in a protic medium was investigated by DFT calculations at the B3LYP/6-311G(d,p) level of theory as a model reaction for the deamination reaction of 5,6-saturated cytosine derivatives. Two pathways were found. Pathway dhA, which can explain the deamination in it protic Medium at acidic pH, and pathway dhBt, more representative of the reaction in a protic medium at neutral pH. Pathway dhA is a two-step mechanism initiated by the nucleophilic addition of a water molecule to carbon C4 of N3-protonated 5,6-dihydrocytosine with the assistance of a second water molecule, followed by elimination of ail ammonium cation to form 5.6-dihydrouracil. The nucleophilic addition is rate-determining, with ail activation free energy of 116.0 kJ/mol in aqueous solution. Pathway dhBt is a four-step mechanism which starts with the water-assisted tautomerization of 5,6-dihydrocytosine to form the imino tautomer. This intermediate undergoes nucleophilic addition of water to carbon C4, which after protonation eliminates ail ammonium cation, as in pathway dhA. The nucleophilic addition is again rate-determining, with ail activation free energy of 113.3 kJ/mol in aqueous solution. The latter value is about 25 kJ/mol lower than its Counterpart for cytosine, in agreement with the experimental observation that 5,6-saturated cytosine derivatives exhibit a much shorter lifetime in aqueous solution than their unsaturated Counterparts. The evaluation of reactivity indices derived from conceptual DFT leads to the conclusion that this lower activation free energy can be attributed to a larger local electrophilic power of carbon C4 in 5.6-saturated derivatives.
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| 6. |
- Labet, Vanessa, et al.
(författare)
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Hydrolytic Deamination of 5-Methylcytosine in Protic Medium : A Theoretical Study
- 2009
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Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 113:11, s. 2524-2533
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism for the deamination reaction of 5-methylcytosine with H2O in protic medium was investigated using DFT calculations at the B3LYP/6-311G(d,p) level of theory. Two pathways were found. Pathway 5mA is a two-step mechanism where the N3-protonated 5-MeCyt undergoes a nucleophilic attack to carbon C4 by a water dimer before the elimination of an ammonium cation. Pathway 5mB is a three-step mechanism where neutral 5-MeCyt is directly attacked by a water dimer. The resulting intermediate is then protonated to allow the elimination of an ammonium cation. Both pathways lead to the formation of thymine in interaction with an ammonium cation and a water molecule. Pathway 5mA can explain the spontaneous deamination of 5-MeCyt in protic medium at acidic pH, whereas pathway 5mB is more representative of the deamination in protic medium at neutral pH. The nucleophilic addition of the water dimer is rate-determining in both pathways and is associated with an activation free energy in aqueous solution of 137.4 kJ/mol for pathway 5mA and 134.1 kJ/mol for pathway 5mB. This latter value is in agreement with the experimental observation that 5-MeCyt deaminates four- to fivefold faster than Cyt at neutral pH. Both electrostatic and electron-transfer contributions appear to have significant importance. In vacuum, the former one dominates when the substrate is positively charged and the latter one when it is neutral.
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| 7. |
- Labet, Vanessa, et al.
(författare)
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Mechanism of nitric oxide induced deamination of cytosine
- 2009
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Ingår i: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 11:14, s. 2379-2386
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Tidskriftsartikel (refereegranskat)abstract
- A five-step mechanism is proposed for the NO center dot-induced deamination of cytosine. It has been investigated using DFT calculations, including both explicit water molecules and a bulk solvent model to mimic an aqueous environment. According to this mechanism, cytosine first undergoes tautomerization with the assistance of a water molecule from the bulk. A NO+ cation produced by the autooxidation of NO center dot is subsequently added to the exocyclic imino group of the cytosine imine tautomer. The resulting adduct is able to undergo a tautomerization step with the participation of a water molecule to produce a cytosine in which a -N2OH group is attached to carbon C4. Protonation of the oxygen of the latter gives a water molecule which dissociates instantaneously, leading to a pyrimidinic diazonium cation. This constitutes the rate-determining step of the mechanism with an activation free energy of 92.6 kJ mol(-1). The last step, which is highly exergonic, represents the driving force of the reaction. It is the substitution of the -N-2(+) terminal group by a water molecule which simultaneously allows the transfer of one of the two hydrogens to the bulk. Thus, the two products of the reaction consist of a nitrogen molecule and the enol tautomer of uracil in equilibrium with the keto form.
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| 8. |
- Labet, Vanessa, et al.
(författare)
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Proton catalyzed hydrolytic deamination of cytosine : a computational study
- 2008
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Ingår i: Theoretical Chemistry accounts. - Berlin Heidelberg : Springer. - 1432-881X .- 1432-2234. ; 120:4-6, s. 429-435
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Tidskriftsartikel (refereegranskat)abstract
- Two pathways involving proton catalyzed hydrolytic deamination of cytosine (to uracil) are investigated at the PCM-corrected B3LYP/6-311G(d,p) level of theory, in the presence of an additional catalyzing water molecule. It is concluded that the pathway involving initial protonation at nitrogen in position 3 of the ring, followed by water addition at C4 and proton transfer to the amino group, is a likely route to hydrolytic deamination. The rate determining step is the addition of water to the cytosine, with a calculated free energy barrier in aqueous solution of G==140 kJ/mol. The current mechanism provides a lower barrier to deamination than previous work based on OH− catalyzed reactions, and lies closer to the experimental barrier derived from rate constants (Ea = 117 ± 4kJ/mol).
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| 9. |
- Labet, Vanessa, et al.
(författare)
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UV-induced formation of the thymine–thymine pyrimidine (6-4) pyrimidone photoproduct – a DFT study of the oxetane intermediate ring opening.
- 2013
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Ingår i: Photochemical and Photobiological Sciences. - : Springer Science and Business Media LLC. - 1474-905X .- 1474-9092. ; 12:8, s. 1509-1516
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism by which the hypothetical oxetane/azetidine intermediate formed during the photochemical process leading to pyrimidine (6-4) pyrimidone photoproducts when DNA is submitted to UV radiation opens is investigated computationally by DFT using a 5’-TT-3’ dinucleoside monophosphate as a structural model. First, the feasibility of an intramolecular mechanism involving one proton transfer inducing opening of the oxetane ring is examined. It results in a very high Gibbs energy of activation (+166 kJ mol−1) and quite a low Gibbs energy of reaction (−35 kJ mol−1). The protonation state of the phosphate group is shown to have little effect while the bulk effect of an aqueous environment modeled by the Polarizable Continuum Model method lowers slightly the activation barrier (by about 10–20 kJ mol−1), not enough to explain the fact that the oxetane intermediate is not observed experimentally. Then the catalytic effect of water molecules on the reaction pathway is studied by including either 1 or 2 assisting water molecules in the chemical system. The resulting activation barrier is considerably lowered and in the most favorable situation – a phosphate group deprotonated and 2 assisting water molecules – the Gibbs energy activation is as low as +44 kJ mol−1 and the Gibbs energy of reaction is quite favorable: −79 kJ mol−1, suggesting that in biological systems the oxetane ring opening process proceeds with explicit intervention of water molecules from the environment.
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