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
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
Affiliations
Daria L. Melnikova
Institute of Physics, Kazan Federal University, Kremlevskaya 16a, 420111 Kazan, Russia
Zilya F. Badrieva
Institute of Physics, Kazan Federal University, Kremlevskaya 16a, 420111 Kazan, Russia
Mikhail A. Kostin
Institute of Chemistry, St. Petersburg State University, Universitetskiy pr. 26, 198504 St. Petersburg, Russia
Corina Maller
Institute of Physical and Theoretical Chemistry, Graz University of Technology, NAWI Graz, Stremayrgasse 9, 8010 Graz, Austria
Monika Stas
Department of Chemistry, Opole University, Oleska Street 48, 45-052 Opole, Poland
Aneta Buczek
Department of Chemistry, Opole University, Oleska Street 48, 45-052 Opole, Poland
Malgorzata A. Broda
Department of Chemistry, Opole University, Oleska Street 48, 45-052 Opole, Poland
Teobald Kupka
Department of Chemistry, Opole University, Oleska Street 48, 45-052 Opole, Poland
Anne-Marie Kelterer
Institute of Physical and Theoretical Chemistry, Graz University of Technology, NAWI Graz, Stremayrgasse 9, 8010 Graz, Austria
Peter M. Tolstoy
Institute of Chemistry, St. Petersburg State University, Universitetskiy pr. 26, 198504 St. Petersburg, Russia
Vladimir D. Skirda
Institute of Physics, Kazan Federal University, Kremlevskaya 16a, 420111 Kazan, Russia
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.
