Theoretically describing the 17O magnetic shielding constant of biomolecular systems: uracil and 5-fluorouracil in water environment

Abstract

The nuclear magnetic resonance chemical shielding of 17O is of great importance for biomolecular characterization in water environment. In these systems, oxygen atoms occupy important positions and are involved in hydrogen bonds with the water environment. In this work, different solvation models are used for the theoretical determination of the 17O chemical shielding of the nucleobase uracil and the substituted 5-fluorouracil in aqueous environment. Continuum, discrete and explicit solvent models are used, and an analysis is made of the role played by the solute polarization due the solvent. The best results are obtained using the sequential quantum mechanics/molecular mechanics methodology using an iterative procedure for the solute polarization, but a good compromise is obtained by using the electronic polarization provided by the polarizable continuum model. Quantum mechanical calculations of the chemical shieldings are made using density-functional theory in two different exchange–correlation approximations. Using an iterative procedure for the solute polarization and the mPW1PW91/aug-pcS-2 model in the electrostatic approximation, we obtained magnetic shielding constants for the two O atoms of uracil within 2 ppm of the experimental results. For 5-fluorouracil, the theoretical results, with the same model, are again in good agreement with the experimental values. An analysis of the influence of the solute–solvent hydrogen bonds in the chemical shielding of uracil case is also made, and it is concluded that the most important contribution to the calculated shielding derives from the electrostatic contribution to the solute–solvent interaction.