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.

Post-translational modified thiazole–amino acid (Xaa–Tzl) residues have been found in macrocyclic peptides (e.g., thiopeptides and cyanobactins), which mostly inhibit protein synthesis in Gram + bacteria. Conformational study of the series of model compounds containing this structural motif with alanine, dehydroalanine, dehydrobutyrine and dehydrophenylalanine were performed using DFT method in various environments. The solid-state crystal structure conformations of thiazole–amino acid residues retrieved from the Cambridge Structural Database were also analysed. The studied structural units tend to adopt the unique semi-extended β2 conformation; which is stabilised mainly by N–H⋯N_Tzl hydrogen bond, and for dehydroamino acids also by π-electron conjugation. The conformational preferences of amino acids with a thiazole ring were compared with oxazole analogues and the role of the sulfur atom in stabilising the conformations of studied peptides was discussed.

Replacement of the main chain peptide bond by imidazole ring seems to be a promising tool for the peptide-based drug design, due to the specific prototropic tautomeric as well as amphoteric properties. In this study, we present that both tautomer and pH change can cause a conformational switch of the studied residues of alanine (1–4) and dehydroalanine (5–8) with the C-terminal peptide group replaced by imidazole. The DFT methods are applied and an environment of increasing polarity is simulated. The conformational maps (Ramachandram diagrams) are presented and the stability of possible conformations is discussed. The neutral forms, tautomers τ (1) and π (2), adapt the conformations αRτ (φ, ψ = − 75°, − 114°) and C7eq (φ, ψ = − 75°, 66°), respectively. Their torsion angles ψ differ by about 180°, which results in a considerable impact on the peptide chain conformation. The cation form (3) adapts both these conformations, whereas the anion analogue (4) prefers the conformations C5 (φ, ψ = − 165°, − 178°) and β2 (φ, ψ ~ − 165°, − 3°). Dehydroamino acid analogues, the tautomers τ (5) and π (6) as well as the anion form (8), have a strong tendency toward the conformations β2 (φ, ψ = − 179°, 0°) and C5 (φ, ψ = − 180°, 180°). The preferences of the protonated imidazolium form (7) depend on the environment. The imidazole ring, acting as a donor or acceptor of the hydrogen bonds created within the studied residues, has a profound effect on the type of conformation.