Solvation of Uracil and Its Derivatives by DMSO: A DFT-Supported ¹H NMR and ¹³C NMR Study

Abstract

H NMR and C NMR spectra of uracil, thymine, 5-hydroxymethyluracil, 5,6-dihydrouracil, and 5,6-dihydrothymine in DMSO-d solutions have been measured. Additionally, molecular structures as well as NMR parameters of these compounds and their various solvates have been calculated using DFT B3LYP/6-311++G(2d,p) PCM(DMSO) method. The analysis of the chemical shift data for these compounds has shown that, indeed, in DMSO solutions they occur as equilibrium mixtures of free molecules and solvates in which solute and solvent molecules are joined by NH···O or OH···O hydrogen bonds. The populations of particular species present in the solutions have been estimated. Moreover, it has been found that 5,6-dihydrothymine exists in DMSO solution preferentially in conformation with the methyl group occupying the pseudoequatorial position. This finding is based on the molecular energy calculations and remains in full agreement with the interpretation of NMR data and theoretical calculations of NMR parameters.

Solvent-Dependent Structures of Natural Products Based on the Combined Use of DFT Calculations and 1H-NMR Chemical Shifts

“…The resulting chemical shifts in DMSO-d 6 (δ = 11.41), acetone-d 6 (δ = 10.21) and CDCl 3 (δ = 6.18) clearly indicate that hydrogen bond between the C(3)–OH group and DMSO-d 6 is more efficient than in acetone-d 6 and significantly stronger than in CDCl 3 . This demonstrates the great sensitivity of 1 H-NMR chemical shifts to both intra- and intermolecular hydrogen bond [26,27,28,29,30,40,41,42,43,44,45,46,47,48].…”

Conformational Equilibrium of Cinchonidine in C6D12 Solution. Alternative NMR/DFT Approach

“…It is well-known that solvents affect NMR parameters and that inclusion of this phenomenon into a theoretical model, albeit possible, unavoidably introduces some uncertainty to the results of theoretical predictions of NMR parameters. ,− When investigating such a complex case as cinchonidine, this fact has to be taken into account. In order to minimize possible difficulties due to the solvent, we have decided to limit at the moment the study to the NMR spectra of our object in cyclohexane- d 12 , the inert solvent which is not expected to form any specific solute–solvent complexes.…”

Solvation of Amides in DMSO and CDCl3: An Attempt at Quantitative DFT-Based Interpretation of 1H and 13C NMR Chemical Shifts

“…Obviously, the structures obtained that way represent local energy minima rather than the global minimum. We have a basis to believe that this fact had only marginal influence on the values of NMR parameters of interest . The problem of the theoretical NMR calculations for supermolecules was addressed in more detail in our previous work .…”

“…Actually, both considered solvents are able to form hydrogen bonds with appropriate solutes, CDCl 3 as a weak hydrogen donor and polar aprotic DMSO as a strong hydrogen acceptor. 6,8,10,33,34 In such a situation, it is not a surprise that attempts at theoretical prediction of solvent effects assuming the solvent to be a polarizable continuum are only moderately successful. [16][17][18]35,36 In the following, we show that in order to reproduce experimental chemical shifts with sufficient accuracy for solutes such as amides, the specific solvent−solute interactions have to be taken into account in the theoretical model, in addition to the bulk solvent effects.…”

“…We have a basis to believe that this fact had only marginal influence on the values of NMR parameters of interest. 10 The problem of the theoretical NMR calculations for supermolecules was addressed in more detail in our previous work. 10 In the second step, the magnetic shielding parameters were calculated using B3LYP and PBE0 (PBE1PBE) 52 functionals and the same basis set as that during the structure optimization.…”