Factors Governing the Chemical Stability and NMR Parameters of Uracil Tautomers and Its 5-Halogen Derivatives

Rzepiela, Kacper; Buczek, Aneta; Kupka, Teobald; Broda, Małgorzata A.

doi:10.3390/molecules25173931

Cited by 10 publications

(8 citation statements)

References 74 publications

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“…1 mg/mL [18]) and its solutions are often prepared in strongly basic media which also increases the side effects of the treatment [19]. The molecule of 5-FU, as a typical pyrimidine base, is subject to tautomeric equilibria between several structural isomers (NH/OH tautomers) [20][21][22]. Despite the possible existence of six tautomers, only one of them (diketo C=O/C=O form, see Figure 1a) is present practically exclusively in aqueous solutions [23] and this isomer is active as a chemotherapeutic agent [24,25].…”

Section: Introductionmentioning

confidence: 99%

On Complex Formation between 5-Fluorouracil and β-Cyclodextrin in Solution and in the Solid State: IR Markers and Detection of Short-Lived Complexes by Diffusion NMR

et al. 2020

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In this work, the nuclear magnetic resonance (NMR) and IR spectroscopic markers of the complexation between 5-fluorouracil (5-FU) and β-cyclodextrin (β-CD) in solid state and in aqueous solution are investigated. In the attenuated total reflectance(ATR) spectra of 5-FU/β-CD products obtained by physical mixing, kneading and co-precipitation, we have identified the two most promising marker bands that could be used to detect complex formations: the C=O and C-F stretching bands of 5-FU that experience a blue shift by ca. 8 and 2 cm–1 upon complexation. The aqueous solutions were studied by NMR spectroscopy. As routine NMR spectra did not show any signs of complexation, we have analyzed the diffusion attenuation of spin–echo signals and the dependence of the population factor of slowly diffusing components on the diffusion time (diffusion NMR of pulsed-field gradient (PFG) NMR). The analysis has revealed that, at each moment, ~60% of 5-FU molecules form a complex with β-CD and its lifetime is ca. 13.5 ms. It is likely to be an inclusion complex, judging from the independence of the diffusion coefficient of β-CD on complexation. The obtained results could be important for future attempts of finding better methods of targeted anticancer drug delivery.

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Section: Introductionmentioning

confidence: 99%

On Complex Formation between 5-Fluorouracil and β-Cyclodextrin in Solution and in the Solid State: IR Markers and Detection of Short-Lived Complexes by Diffusion NMR

et al. 2020

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“…Uracil is an important component related to information transfer and replication in living systems. Its 5-halogen modifications are used in anticancer and antifungal treatment [ 59 , 61 , 62 , 63 ]. Modifications of uracil, including replacing the oxygen atom with sulfur [ 64 ], also changes its biological activity.…”

Section: Resultsmentioning

confidence: 99%

Electron Correlation or Basis Set Quality: How to Obtain Converged and Accurate NMR Shieldings for the Third-Row Elements?

et al. 2022

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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.

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“…1a, is most stable. [16][17][18][19] According to X-ray studies, uracil is found only in the diketo form in the solid phase, and in the same form, it exists in water. As shown in Fig.…”

Section: Introductionmentioning

confidence: 99%

Uracil–water interaction revisited – in search of single H-bonded secondary minima

Buczek,

Rzepiela,

Kupka

et al. 2024

Phys. Chem. Chem. Phys.

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Factors Governing the Chemical Stability and NMR Parameters of Uracil Tautomers and Its 5-Halogen Derivatives

Cited by 10 publications

References 74 publications

On Complex Formation between 5-Fluorouracil and β-Cyclodextrin in Solution and in the Solid State: IR Markers and Detection of Short-Lived Complexes by Diffusion NMR

On Complex Formation between 5-Fluorouracil and β-Cyclodextrin in Solution and in the Solid State: IR Markers and Detection of Short-Lived Complexes by Diffusion NMR

Electron Correlation or Basis Set Quality: How to Obtain Converged and Accurate NMR Shieldings for the Third-Row Elements?

Uracil–water interaction revisited – in search of single H-bonded secondary minima

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