Asian Journal of Physics Vol. 35, Nos 4 – 6 (2026) 209-223

Hydration on the tautomerism in the anticarcinogenic drug 5-fluorouracil

M Alcolea Palafoxa , Shalini Singhalb, Surabhi Singhalc, J K Vatsd, M K Gandhie and V K Rastogie
aDepartamento de Química-Física I, Facultad de Ciencias Químicas, Universidad Complutense, Madrid-28040, Spain
bDepartment of  Laboratory Medicine, All India Institute of Medical Sciences, New Delhi-110 029 , India
cDepartment of Physics, Government Girls Degree College, Kharkhauda (Meerut)-245 206, India
dDepartment of Physics, Ram Jaipal College (A Constituent Unit of Jai Prakash University), Chapra-841 301, Bihar, India
eIndian Spectroscopy Society, KC-68/1, Old Kavinagar, Ghaziabad-201 002, India

The tautomerism of 5-fluorouracil (5-FU) was investigated in the gas phase and in solution. In the present work seven tautomers of 5-FU have been predicted and optimized. Six of them are related to those of uracil molecule, with the same stability order. Solvent effects were considered using a variable number (1-10) of explicit water molecules surrounding 5-FU in order to simulate the first hydration shell. More than 100 cluster structures with water were analyzed. Attachment of a fluorine atom changes the relative free energy order of uracil tautomers in the gas phase and in solution. For cases where literature data are available, the computed values were in good agreement with previous experimental and theoretical studies. Depending on the nature of the tautomers, cyclic, distributed water molecules, or clustered structures are formed. The hydration energies of various tautomers are large and vary dramatically between tautomers. The microhydrated environment stabilizes remarkably the enol forms more than the canonical keto one, although this one continues being the most stable. Several general conclusions were underlined. © Anita Publications. All rights reserved.
Doi: 1XX
Keywords: 5-Fluorouracil, Hydration shell, Solvent effect, Tautomerism, Chemotherepatic agent, Radio-sensitization properties.

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