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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731325/ https://www.ncbi.nlm.nih.gov/pubmed/33287255 http://dx.doi.org/10.3390/molecules25235706 |
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author | Melnikova, Daria L. Badrieva, Zilya F. Kostin, Mikhail A. Maller, Corina Stas, Monika Buczek, Aneta Broda, Malgorzata A. Kupka, Teobald Kelterer, Anne-Marie Tolstoy, Peter M. Skirda, Vladimir D. |
author_facet | Melnikova, Daria L. Badrieva, Zilya F. Kostin, Mikhail A. Maller, Corina Stas, Monika Buczek, Aneta Broda, Malgorzata A. Kupka, Teobald Kelterer, Anne-Marie Tolstoy, Peter M. Skirda, Vladimir D. |
author_sort | Melnikova, Daria L. |
collection | PubMed |
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(−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. |
format | Online Article Text |
id | pubmed-7731325 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77313252020-12-12 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 Melnikova, Daria L. Badrieva, Zilya F. Kostin, Mikhail A. Maller, Corina Stas, Monika Buczek, Aneta Broda, Malgorzata A. Kupka, Teobald Kelterer, Anne-Marie Tolstoy, Peter M. Skirda, Vladimir D. Molecules Article 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. MDPI 2020-12-03 /pmc/articles/PMC7731325/ /pubmed/33287255 http://dx.doi.org/10.3390/molecules25235706 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Melnikova, Daria L. Badrieva, Zilya F. Kostin, Mikhail A. Maller, Corina Stas, Monika Buczek, Aneta Broda, Malgorzata A. Kupka, Teobald Kelterer, Anne-Marie Tolstoy, Peter M. Skirda, Vladimir D. 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 | 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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731325/ https://www.ncbi.nlm.nih.gov/pubmed/33287255 http://dx.doi.org/10.3390/molecules25235706 |
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