Effect of hydration on the stability and tautomerisms of different isomers of uracil

Abstract

Thermodynamic and structural properties of isolated, hydrated and solvated forms of twelve isomers of uracil were studied, theoretically. It was found that the di-keto tautomer is the most stable isomer in gas and aqueous phases and in hydrated forms. Internal proton transfers and O-H rotations in uracil were studied employing B3LYP and MP2 methods in gas phase. Activation energies (E a ) and Gibbs free energies (∆G # ) of the isomerization processes were calculated. The calculated activation energies of the proton transfer reactions were in the range of 110-180 kJ/mol and the energy barriers of internal O-H rotations were generally smaller than 40 kJ/mol. The high energy barriers of the proton transfers indicate that proton transfers are hard to achieve.Therefore, catalysis effect of one, two and three water molecules on the proton transfer processes in the hydrated isomers of uracil was investigated. The calculations showed that water molecules lower the energy barriers of the proton transfer reactions and catalyze the tautomerism processes in uracil.

Exploring Free Energy Profiles of Uracil and Cytosine Reactions with Formaldehyde

“…The tautomers of uracil 1b–1f are all more than 10 kcal/mol higher in energy than uracil and are expected to have minimal presence at equilibrium in aqueous solution. Gas chromatography mass spectrometry (ion trap) experiments have confirmed the existence of these tautomers, although relative energies have only been determined computationally with a variety of methods (DFT, MP2, CCSD), − with results similar to our present numbers. Of the tautomers, 1b has the lowest energy, 10.5 kcal/mol higher than 1a .…”

Nanohydration of uracil: emergence of three-dimensional structures and proton-induced charge transfer

“…11,12 Microhydration of the uracil nucleobase has been investigated by many authors in the past using a variety of theoretical and experimental methods, especially in relation with its interactions with protons or electrons. [13][14][15][16][17][18][19][20][21][22] While electron trapping is suspected to be one major cause of strand breaking, [23][24][25][26] proton isomerism and acidity are important issues as well owing to the possible occurence of point mutations due to rare tautomers. [27][28][29] So far, there has been general consensus among theoreticians 14,15,20,21,[30][31][32][33][34] that neutral uracil should be initially hydrated in a peripheral locked chain fashion close to the molecular plane, although differences have been noted for the anionic 15 and deprotonated 20 species.…”

Effect of Mono- and Di-hydration on the Intramolecular Proton Transfers and Stability of Cyanuric Acid Isomers: A DFT Study

“…These studies show that the energy barriers of the intramolecular proton transfers decrease as these reactions are catalyzed by water molecules. 14,15,22,23 The cyanuric acid isomers can be hydrated from different sites. Therefore, we considered different paths for hydration of each isomer (a, b and c).…”

“…Keto-enol tautomerism is intramolecular proton transfer which has been well-studied for many important molecules. 13 15 Kroke et al, 16 and Liang et al, 1 studied keto-enol tautomerisms in cyanuric acid. Liang et al, 1 calculated the energy barriers for the interconversion of the tri-keto isomer to the tri-enol isomer through sequential proton transfer.…”