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
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 phys...
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MDPI AG
2020-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/23/5706 |
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| author | Daria L. Melnikova Zilya F. Badrieva Mikhail A. Kostin Corina Maller Monika Stas Aneta Buczek Malgorzata A. Broda Teobald Kupka Anne-Marie Kelterer Peter M. Tolstoy Vladimir D. Skirda |
| author_facet | Daria L. Melnikova Zilya F. Badrieva Mikhail A. Kostin Corina Maller Monika Stas Aneta Buczek Malgorzata A. Broda Teobald Kupka Anne-Marie Kelterer Peter M. Tolstoy Vladimir D. Skirda |
| author_sort | Daria L. Melnikova |
| collection | DOAJ |
| description | 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<sup>−1</sup> 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. |
| first_indexed | 2024-03-10T14:21:22Z |
| format | Article |
| id | doaj.art-65abf39edefe44e8bba9726a783f95fc |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T14:21:22Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-65abf39edefe44e8bba9726a783f95fc2023-11-20T23:21:40ZengMDPI AGMolecules1420-30492020-12-012523570610.3390/molecules25235706On 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 NMRDaria L. Melnikova0Zilya F. Badrieva1Mikhail A. Kostin2Corina Maller3Monika Stas4Aneta Buczek5Malgorzata A. Broda6Teobald Kupka7Anne-Marie Kelterer8Peter M. Tolstoy9Vladimir D. Skirda10Institute of Physics, Kazan Federal University, Kremlevskaya 16a, 420111 Kazan, RussiaInstitute of Physics, Kazan Federal University, Kremlevskaya 16a, 420111 Kazan, RussiaInstitute of Chemistry, St. Petersburg State University, Universitetskiy pr. 26, 198504 St. Petersburg, RussiaInstitute of Physical and Theoretical Chemistry, Graz University of Technology, NAWI Graz, Stremayrgasse 9, 8010 Graz, AustriaDepartment of Chemistry, Opole University, Oleska Street 48, 45-052 Opole, PolandDepartment of Chemistry, Opole University, Oleska Street 48, 45-052 Opole, PolandDepartment of Chemistry, Opole University, Oleska Street 48, 45-052 Opole, PolandDepartment of Chemistry, Opole University, Oleska Street 48, 45-052 Opole, PolandInstitute of Physical and Theoretical Chemistry, Graz University of Technology, NAWI Graz, Stremayrgasse 9, 8010 Graz, AustriaInstitute of Chemistry, St. Petersburg State University, Universitetskiy pr. 26, 198504 St. Petersburg, RussiaInstitute of Physics, Kazan Federal University, Kremlevskaya 16a, 420111 Kazan, RussiaIn 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<sup>−1</sup> 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.https://www.mdpi.com/1420-3049/25/23/57065-FUβ-CDinclusion complexIRNMRmolecular modeling |
| spellingShingle | Daria L. Melnikova Zilya F. Badrieva Mikhail A. Kostin Corina Maller Monika Stas Aneta Buczek Malgorzata A. Broda Teobald Kupka Anne-Marie Kelterer Peter M. Tolstoy Vladimir D. Skirda 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 Molecules 5-FU β-CD inclusion complex IR NMR molecular modeling |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | 5-FU β-CD inclusion complex IR NMR molecular modeling |
| url | https://www.mdpi.com/1420-3049/25/23/5706 |
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