Correlated ab initio study of nucleic acid bases and their tautomers in the gas phase, in a microhydrated environment and in aqueous solution. Part 4. Uracil and thymine

Abstract

Altogether 13 keto and enol tautomers of uracil and 13 keto and enol tautomers of thymine were studied theoretically in the gas phase, in a microhydrated environment (1 and 2 water molecules) and in a water environment. Bulk water was described using the thermodynamic integration method, Conductor-like polarizable continuum model (C-PCM, COSMO) and hybrid model (C-PCM + 1-2 explicit water molecules). The structures of various tautomers were determined at the RI-MP2 level using the TZVPP basis set while relative energies were determined at the CCSD(T) level. The relative free energies at 298 K were based on the relative energies mentioned above and zero-point vibration energies, and temperature dependent enthalpy terms and entropies evaluated at the MP2/6-31G** level. The effect of bulk solvent on the relative stability of uracil and thymine tautomers was studied using molecular dynamics free energy calculations by means of the thermodynamic integration method and self-consistent reaction field. Despite the completely different nature of these methods they provide comparable solvation free energies. Besides theoretical investigation, experimental detection of uracil and thymine tautomers was performed by means of steady-state fluorescence. We conclude that it is impossible to utilize the method used by Suwaiyan and Morsy (M. A. Morsy, A. M. Al-Somali and A. Suwaiyan, J. Phys. Chem. B, 1999, 103(50), 11205) for tautomer detection, even if a very sensitive fluorimeter is used. Theoretical relative energies and free energies for isolated uracil and thymine tautomers support the existence of the canonical form only. The microhydrated environment and bulk solvent stabilize enol forms more than the canonical keto one, but gas phase destabilization of these enol forms is too high. Population of rare enol forms of uracil and thymine in bulk water will thus be very low and canonical structure will also be dominant in this phase.

The effect of microhydration on ionization energies of thymine

“…There are several tautomers of thymine; however, the energy gap between the canonical form and next most stable tautomer is more than 10 kcal/mol [39] in the gas phase. Since we used thermal vaporization to generate thymine in the gas phase, there is not enough energy to populate higher-lying tautomers.…”

It Is Important to Compute Intramolecular Hydrogen Bonding in Drug Design?

“…Useful information can be obtained from experimental gas-phase hydration/solvation studies augmented with theoretical calculations [108][109][110][111][112][113][114][115][116] or specific theoretical calculations for hydrated amino acid side chains, nucleotid base and sugar models [117][118][119][120][121].…”

Bio-Inspired Membranes for Advanced Polymer Electrolyte Fuel Cells. Anhydrous Proton-Conducting Membrane via Molecular Self-Assembly

“…Table 2 summarizes the results of conducting properties of the composite membrane studied in the present work. 62,63,82,84,91,94,95,97,99,101 In most cases, the conductivity ranged from 1 Â 10 À4 to 1 Â 10 À2 S cm À1 , and the activation energy ranged from 0.2 to 0.5 eV. The maximum conductivity was obtained for polystyrene sulfonic acid/12-phosphotungstic acid (PSS-PWA) composites (1 Â 10 À2 S cm À1 at 180 C) and the activation energy was 0.4-0.5 eV.…”

“…Uracil have been known to arrange a lactam structure under neutral conditions and a lactam-lactim structure (lactamlactim tautomerism) under acidic conditions. 99,100 From TG-DTA data, the CP-50 mol % U composite material was stable at the intermediate temperatures ( 150 C) (see (3) in Fig. 11).…”