Rotaxanes can be regarded as storage systems for their wheel components, which broadens their application potential as a complement to the supramolecular systems that retain a mechanically interlocked structure. However, utilising rotaxanes in this way requires a method to release the wheel while preserving the integrity of all molecular constituents. Herein, we present simple rotaxanes based on cucurbit[6]uril (CB6), with an axis equipped with an additional binding motif that enables the binding of another macrocycle, cucurbit[7]uril (CB7). We demonstrate that the driving force behind the wheel dethreading originates from the binding of the signalling macrocycle to the allosteric site, leading to an increase in the system's strain. Consequently, the CB6 wheel leaves the rotaxane station overcoming the mechanical barrier. Portal-portal repulsive interactions between the two cucurbituril units play a crucial role in this process. Thus, the repulsive strength and the related rate of slipping off can be finely tuned by the length of the allosteric binding motif. Finally, we show that the CB6 wheel can be utilised within complexes with other guests in the mixture once released from the rotaxane.

• Publication type
• Journal Article MeSH

Novel binding motifs suitable for the construction of multitopic guest-based molecular devices (e.g., switches, sensors, data storage, and catalysts) are needed in supramolecular chemistry. No rigid, aliphatic binding motif that allows for axial disubstitution has been described for cucurbit[6]uril (CB6) so far. We prepared three model guests combining spiro[3.3]heptane and bicyclo[1.1.1]pentane centerpieces with imidazolium and ammonium termini. We described their binding properties toward CB6/7 and α-/β-CD using NMR, titration calorimetry, mass spectrometry, and single-crystal X-ray diffraction. We found that a bisimidazolio spiro[3.3]heptane guest forms inclusion complexes with CB6, CB7, and β-CD with respective association constants of 4.0 × 104, 1.2 × 1012, and 1.4 × 102. Due to less hindering terminal groups, the diammonio analogue forms more stable complexes with CB6 (K = 1.4 × 106) and CB7 (K = 3.8 × 1012). The bisimidazolio bicyclo[1.1.1]pentane guest forms a highly stable complex only with CB7 with a K value of 1.1 × 1011. The high selectivity of the new binding motifs implies promising potential in the construction of multitopic supramolecular components.

• Publication type
• Journal Article MeSH

Purine nucleosides represent an interesting group of nitrogen heterocycles, showing a wide range of biological effects. In this study, we designed and synthesized a series of 6,9-disubstituted and 2,6,9-trisubstituted purine ribonucleosides via consecutive nucleophilic aromatic substitution, glycosylation, and deprotection of the ribofuranose unit. We prepared eight new purine nucleosides bearing unique adamantylated aromatic amines at position 6. Additionally, the ability of the synthesized purine nucleosides to form stable host-guest complexes with β-cyclodextrin (β-CD) was confirmed using nuclear magnetic resonance (NMR) and mass spectrometry (ESI-MS) experiments. The in vitro antiproliferative activity of purine nucleosides and their equimolar mixtures with β-CD was tested against two types of human tumor cell line. Six adamantane-based purine nucleosides showed an antiproliferative activity in the micromolar range. Moreover, their effect was only slightly suppressed by the presence of β-CD, which was probably due to the competitive binding of the corresponding purine nucleoside inside the β-CD cavity.

• Keywords
• adamantane, antiproliferative activity, glycosylation, nucleoside, purine, β-cyclodextrin,
• MeSH
• Adamantane * pharmacology   MeSH
• beta-Cyclodextrins * pharmacology   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Nucleosides pharmacology   chemistry   MeSH
• Purine Nucleosides pharmacology   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Adamantane * MeSH
• beta-Cyclodextrins * MeSH
• Nucleosides MeSH
• Purine Nucleosides MeSH