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New Insight into the Substituent Effects on the Hydrolytic Deamination of Saturated and Unsaturated Cytosine
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  • Kabir Uddin,
  • Md. Islam,
  • Shahidul Islam,
  • Raymond Poirier
Kabir Uddin
North South University

Corresponding Author:[email protected]

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Md. Islam
Bangladesh Council of Scientific and Industrial Research, BCSIR, Laboratories, Chattogram-4220, Bangladesh
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Shahidul Islam
University of Illinois Chicago
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Raymond Poirier
Memorial University of Newfoundland
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Ab initio calculations were carried out to understand the effect of electron donating groups (EDG) and electron withdrawing groups (EWG) at the C5 position of cytosine (Cyt) and saturated cytosine (H2Cyt) of the deamination reaction. Geometries of the reactants, transition states, intermediates, and products were fully optimized at the B3LYP/6-31G(d,p) level in the gas phase as this level of theory has been found to agree very well with G3 theories. Activation energies, enthalpies, and Gibbs energies of activation along with the thermodynamic properties (ΔE, ΔH, and ΔG) of each reaction were calculated. A plot of the Gibbs energies of activation (ΔG‡) for C5 substituted Cyt and H2Cyt against the Hammett σ-constants reveal a good linear relationship. In general, both EDG and EWG substituents at the C5 position in Cyt results in higher ΔG‡ and lower σ values compared to those of H2Cyt deamination reactions. C5 alkyl substituents (−H, −CH3, −CH2CH3, −CH2CH2CH3) increase ΔG‡ values for Cyt, while the same substituents decrease ΔG‡ values for H2Cyt which is likely due to steric effects. However, the Hammett σ-constants were found to decrease for both the Cyt and H2Cyt. Both ΔG‡ and σ values decrease for the substituents Cl and Br in the reaction Cyt, while ΔG‡ values increase and σ decrease in the reaction H2Cyt. This may be due to high polarizability of bromine which results in a greater stabilization of the transition state in the case of bromine compared to chlorine. Regardless of the substituent at C5, the positive charge on C4 is greater in the TS compared to the reactant complex for both the Cyt and H2Cyt. Moreover, as the charges on C4 in the TS increase compared to reactant, ΔG‡ also increase for the C5 alkyl substituents (-H, −CH3, −CH2CH3, −CH2CH2CH3) in Cyt, while ΔG‡ decrease in H2Cyt. In addition, analysis of the frontier MO energies for the transition state structures shows that there is a correlation between the energy of the HOMO‒LUMO gap and activation energies.
12 Jun 2022Submitted to International Journal of Quantum Chemistry
13 Jun 2022Submission Checks Completed
13 Jun 2022Assigned to Editor
07 Jul 2022Reviewer(s) Assigned
28 Jul 2022Review(s) Completed, Editorial Evaluation Pending
08 Aug 2022Editorial Decision: Revise Minor
18 Aug 20221st Revision Received
20 Aug 2022Submission Checks Completed
20 Aug 2022Assigned to Editor
20 Aug 2022Reviewer(s) Assigned
22 Aug 2022Review(s) Completed, Editorial Evaluation Pending
22 Aug 2022Editorial Decision: Accept
15 Jan 2023Published in International Journal of Quantum Chemistry volume 123 issue 2. 10.1002/qua.27014