REGULAR ARTICLE Theoretically describing the 17 O magnetic shielding constant of biomolecular systems: uracil and 5-fluorouracil in water environment Rodrigo M. Gester • Carlos Bistafa • Herbert C. Georg • Kaline Coutinho • Sylvio Canuto Received: 12 August 2013 / Accepted: 12 November 2013 Ó Springer-Verlag Berlin Heidelberg 2013 Abstract The nuclear magnetic resonance chemical shielding of 17 O 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 theoret- ical determination of the 17 O 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 polariza- tion provided by the polarizable continuum model. Quan- tum 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. Keywords Magnetic shielding  QM/MM methods  Solvent effects  Hydrogen bonds  DFT method 1 Introduction Nuclear magnetic resonance (NMR) is one of the most important spectroscopic techniques in molecular charac- terization [1]. In recent years, it has been widely and suc- cessfully used to characterize biomolecular systems. In this vein, oxygen is one of the most important atoms in both, chemistry and biology. Oxygen is essential in most bio- molecules occupying important positions and often involved in relevant intra- and intermolecular hydrogen- bonded interactions. These features make the oxygen spectrum of great importance in NMR experiments [2, 3]. The 17 O is the only naturally occurring oxygen isotope with nonzero nuclear spin. Its low natural abundance (0.04 %) is reported as the most experimental difficulty and justifies the restricted attention dedicated to this isotope. In fact, there are only few experimental NMR works dealing with 17 O magnetic constants [2–5]. There is then a clear importance in better understanding the magnetic properties of oxygen atoms in biomolecular systems. Although 17 O is found on several biomolecules, there are only a limited number of experimental works that use 17 O NMR to investigate biomolecular systems such as the nucleobases R. M. Gester  C. Bistafa  K. Coutinho  S. Canuto (&) Instituto de Fı ´sica, Universidade de Sa ˜o Paulo, CP 66318, Sa ˜o Paulo, SP 05315-970, Brazil e-mail: canuto@if.usp.br R. M. Gester Faculdade de Fı ´sica, Universidade Federal do Para ´, Maraba ´, PA 68505-080, Brazil H. C. Georg Instituto de Fı ´sica, Universidade Federal de Goia ´s, CP 131, Goia ˆnia, GO 74001-970, Brazil 123 Theor Chem Acc (2014) 133:1424 DOI 10.1007/s00214-013-1424-y