The Effect of Sulphur Atom on the Structure of Biomolecule 2-Thiocytosine in the Gas-Phase, Solid-State, and Hydrated Forms and in DNA–DNA Microhelices as Compared to Canonical Ones

This study is focused on the effects of the sulphur atom in position 2 of the cytosine molecule, 2-thiocytosine (2TC), on the molecular structural parameters in the isolated state, as well as in the hydration, solid state arrangement, Watson–Crick pairs, and DNA–DNA microhelices, as compared to the...

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Main Authors: Mauricio Alcolea Palafox, Valentin Alba Aparicio, Sergio Toninelli Rodriguez, Josefa Isasi Marín, Jitendra Kumar Vats, Vinod Kumar Rastogi
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/3/559
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author Mauricio Alcolea Palafox
Valentin Alba Aparicio
Sergio Toninelli Rodriguez
Josefa Isasi Marín
Jitendra Kumar Vats
Vinod Kumar Rastogi
author_facet Mauricio Alcolea Palafox
Valentin Alba Aparicio
Sergio Toninelli Rodriguez
Josefa Isasi Marín
Jitendra Kumar Vats
Vinod Kumar Rastogi
author_sort Mauricio Alcolea Palafox
collection DOAJ
description This study is focused on the effects of the sulphur atom in position 2 of the cytosine molecule, 2-thiocytosine (2TC), on the molecular structural parameters in the isolated state, as well as in the hydration, solid state arrangement, Watson–Crick pairs, and DNA–DNA microhelices, as compared to the canonical form. The main six tautomers were optimised at the MP2 and CCSD levels, and the sulphur atom does not show any effect on the stability trend of cytosine. The energy difference between <b>T2b</b> and <b>T2a</b> tautomers is twice as low in 2TC (1.15 kJ/mol) than in cytosine (2.69 kJ/mol). The IR and laser Raman spectra of 2TC were accurately assigned using DFT computations and solid-state simulations of the crystal unit cell through several tetramer forms. The results notably improve those previously published by other authors. The effect of explicit water molecules surrounding 2TC up to 30, corresponding to the first and second hydration shells, on geometries and tautomerism was analysed. The Watson–Crick base pairs’ stability (ΔE<sup>CP</sup> = −97.458 kJ/mol) was found to be less than with cytosine (−105.930 kJ/mol). The calculated dipole moment was also lower (4.205 D) than with cytosine (5.793 D). The effect of 2TC on the 5′-dG-dC-dG-3′ and 5′-dA-dC-dA-3′ DNA–DNA optimised microhelices was evaluated through their calculated helical parameters, which indicates a clear deformation of the helix formation. The radius (R) with 2TC appears considerably shorter (6.200 Å) in the 5′-dA-dC-dA-3′ microhelix than that with cytosine (7.050 Å). Because of the special characteristics of the 2TC molecule, it can be used as an anticancer drug.
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spelling doaj-art-96b2fa9376684d0d9785f08c960664cd2025-08-20T03:12:35ZengMDPI AGMolecules1420-30492025-01-0130355910.3390/molecules30030559The Effect of Sulphur Atom on the Structure of Biomolecule 2-Thiocytosine in the Gas-Phase, Solid-State, and Hydrated Forms and in DNA–DNA Microhelices as Compared to Canonical OnesMauricio Alcolea Palafox0Valentin Alba Aparicio1Sergio Toninelli Rodriguez2Josefa Isasi Marín3Jitendra Kumar Vats4Vinod Kumar Rastogi5Departamento de Química-Física, Facultad de Ciencias Químicas, Universidad Complutense, 28040 Madrid, SpainDepartamento de Química-Física, Facultad de Ciencias Químicas, Universidad Complutense, 28040 Madrid, SpainDepartamento de Química-Física, Facultad de Ciencias Químicas, Universidad Complutense, 28040 Madrid, SpainDepartamento de Química Inorgánica, Facultad de Ciencias Químicas, Universidad Complutense, 28040 Madrid, SpainP G Department of Physics, RJC, Jai Prakash University, Chapra 841301, IndiaIndian Spectroscopy Society, KC-68/1, Old Kavinagar, Ghaziabad 201002, IndiaThis study is focused on the effects of the sulphur atom in position 2 of the cytosine molecule, 2-thiocytosine (2TC), on the molecular structural parameters in the isolated state, as well as in the hydration, solid state arrangement, Watson–Crick pairs, and DNA–DNA microhelices, as compared to the canonical form. The main six tautomers were optimised at the MP2 and CCSD levels, and the sulphur atom does not show any effect on the stability trend of cytosine. The energy difference between <b>T2b</b> and <b>T2a</b> tautomers is twice as low in 2TC (1.15 kJ/mol) than in cytosine (2.69 kJ/mol). The IR and laser Raman spectra of 2TC were accurately assigned using DFT computations and solid-state simulations of the crystal unit cell through several tetramer forms. The results notably improve those previously published by other authors. The effect of explicit water molecules surrounding 2TC up to 30, corresponding to the first and second hydration shells, on geometries and tautomerism was analysed. The Watson–Crick base pairs’ stability (ΔE<sup>CP</sup> = −97.458 kJ/mol) was found to be less than with cytosine (−105.930 kJ/mol). The calculated dipole moment was also lower (4.205 D) than with cytosine (5.793 D). The effect of 2TC on the 5′-dG-dC-dG-3′ and 5′-dA-dC-dA-3′ DNA–DNA optimised microhelices was evaluated through their calculated helical parameters, which indicates a clear deformation of the helix formation. The radius (R) with 2TC appears considerably shorter (6.200 Å) in the 5′-dA-dC-dA-3′ microhelix than that with cytosine (7.050 Å). Because of the special characteristics of the 2TC molecule, it can be used as an anticancer drug.https://www.mdpi.com/1420-3049/30/3/559WC pair2-thiocytosinethiopyrimidinevibrational analysismicrohelixDNA
spellingShingle Mauricio Alcolea Palafox
Valentin Alba Aparicio
Sergio Toninelli Rodriguez
Josefa Isasi Marín
Jitendra Kumar Vats
Vinod Kumar Rastogi
The Effect of Sulphur Atom on the Structure of Biomolecule 2-Thiocytosine in the Gas-Phase, Solid-State, and Hydrated Forms and in DNA–DNA Microhelices as Compared to Canonical Ones
Molecules
WC pair
2-thiocytosine
thiopyrimidine
vibrational analysis
microhelix
DNA
title The Effect of Sulphur Atom on the Structure of Biomolecule 2-Thiocytosine in the Gas-Phase, Solid-State, and Hydrated Forms and in DNA–DNA Microhelices as Compared to Canonical Ones
title_full The Effect of Sulphur Atom on the Structure of Biomolecule 2-Thiocytosine in the Gas-Phase, Solid-State, and Hydrated Forms and in DNA–DNA Microhelices as Compared to Canonical Ones
title_fullStr The Effect of Sulphur Atom on the Structure of Biomolecule 2-Thiocytosine in the Gas-Phase, Solid-State, and Hydrated Forms and in DNA–DNA Microhelices as Compared to Canonical Ones
title_full_unstemmed The Effect of Sulphur Atom on the Structure of Biomolecule 2-Thiocytosine in the Gas-Phase, Solid-State, and Hydrated Forms and in DNA–DNA Microhelices as Compared to Canonical Ones
title_short The Effect of Sulphur Atom on the Structure of Biomolecule 2-Thiocytosine in the Gas-Phase, Solid-State, and Hydrated Forms and in DNA–DNA Microhelices as Compared to Canonical Ones
title_sort effect of sulphur atom on the structure of biomolecule 2 thiocytosine in the gas phase solid state and hydrated forms and in dna dna microhelices as compared to canonical ones
topic WC pair
2-thiocytosine
thiopyrimidine
vibrational analysis
microhelix
DNA
url https://www.mdpi.com/1420-3049/30/3/559
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