Abstract
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.
Highlights
NMR spectroscopy has been shown as an indispensable technique for the characterization of both natural products and man-made molecular systems [1,2,3,4,5,6]
The geometries and energies of all possible tautomers of uracil and its 5-halogen derivatives are calculated in the gas phase and in water environment, modelled by the polarizable continuum model (PCM) and the solvent model density (SMD)
We chose a popular B3LYP hybrid density functional for the modelling of uracil and its four 5-halogen derivatives in the gas phase and in water, described by the polarized continuum model (PCM) [64] and the solvation model based on density (SMD) [65] using standard parameters in the Gaussian 16 program package [66]
Summary
NMR spectroscopy has been shown as an indispensable technique for the characterization of both natural products and man-made molecular systems [1,2,3,4,5,6]. The NMR technique of natural products is generally applied, following initial physic-chemical processes of extraction leading to an increased concentration of biologically active compounds [7,8]. On the other hand, localized NMR spectroscopy in vivo is suitable to follow millimolar concentrations of metabolites in living systems [9,10]. The first task is to determine their structure and next to study interactions and functions. Such works are very challenging and usually supported by molecular modelling
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