We report on the density functional theory (DFT) modelling of structural, energetic and NMR parameters of uracil and its derivatives (5-halogenouracil (5XU), X = F, Cl, Br and I) in vacuum and in water using the polarizable continuum model (PCM) and the solvent model density (SMD) approach. On the basis of the obtained results, we conclude that the intramolecular electrostatic interactions are the main factors governing the stability of the six tautomeric forms of uracil and 5XU. Two indices of aromaticity, the harmonic oscillator model of aromaticity (HOMA), satisfying the geometric criterion, and the nuclear independent chemical shift (NICS), were applied to evaluate the aromaticity of uracil and its derivatives in the gas phase and water. The values of these parameters showed that the most stable tautomer is the least aromatic. A good performance of newly designed xOPBE density functional in combination with both large aug-cc-pVQZ and small STO(1M)−3G basis sets for predicting chemical shifts of uracil and 5-fluorouracil in vacuum and water was observed. As a practical alternative for calculating the chemical shifts of challenging heterocyclic compounds, we also propose B3LYP calculations with small STO(1M)−3G basis set. The indirect spin–spin coupling constants predicted by B3LYP/aug-cc-pVQZ(mixed) method reproduce the experimental data for uracil and 5-fluorouracil well.

The problem of aromaticity in heterocyclic rings of uracil and its 5-halogenoderivatives (5XU) was analyzed theoretically by calculating modified harmonic oscillator model of aromaticity (HOMA) for Heterocycle Electron Delocalization (HOMHED), nucleus-independent chemical shift parameters (NICS) and the so-called scan experiments, using helium-3 atom as a magnetic probe. The impact of halogen electronegativity on C5 atom’s NBO charges was also investigated. Water, as a polar environment, has a negligible impact on 5XU aromaticity. The most stable diketo tautomer shows a very low aromaticity while the “rare” dihydroxy form (tautomer No 6) is aromatic and resembles benzene. This is in agreement with traditional drawing of chemical formula of uracil’s six-membered ring, directly showing three alternating single and double bonds in its tautomer No 6. No good correlation between magnetic and geometric indexes of aromaticity for the studied 5XU tautomers was found. Linear correlation between the magnitude of NICS minimum, as well as the distance of the minimum above uracil ring plane center from 3He NMR chemical shift scan plot with respect to halogen electronegativity were observed. A strong linear dependence of magnetic index of aromaticity and the electronegativity of 5X substituent was observed.

The quality of theoretical NMR shieldings calculated at the quantum-chemical level depends on various theoretical aspects, of which the basis set type and size are among the most important factors. Nevertheless, not much information is available on the basis set effect on theoretical shieldings of the NMR-active nuclei of the third row. Here, we report on the importance of proper basis set selection to obtain accurate and reliable NMR shielding parameters for nuclei from the third row of the periodic table. All calculations were performed on a set of eleven compounds containing the elements Na, Mg, Al, Si, P, S, or Cl. NMR shielding tensors were calculated using the SCF-HF, DFT-B3LYP, and CCSD(T) methods, combined with the Dunning valence aug-cc-pVXZ, core-valence aug-cc-pCVXZ, Jensen polarized-convergent aug-pcSseg-n and Karlsruhe x2c-Def2 basis set families. We also estimated the complete basis set limit (CBS) values of the NMR parameters. Widely scattered nuclear shieldings were observed for the Dunning polarized-valence basis set, which provides irregular convergence. We show that the use of Dunning core-valence or Jensen basis sets effectively reduces the scatter of theoretical NMR results and leads to their exponential-like convergence to CBS. We also assessed the effect of vibrational, temperature, and relativistic corrections on the predicted shieldings. For systems with single bonds, all corrections are relatively small, amounting to less than 4% of the CCSD(T)/CBS value. Vibrational and temperature corrections were less reliable for H3PO and HSiCH due to the high anharmonicity of the molecules. An abnormally high relativistic correction was observed for phosphorus in PN, reaching ~20% of the CCSD(T)/CBS value, while the correction was less than 7% for other tested molecules.