Study on the host–guest interactions between tetramethyl cucurbit[6]uril and 2-heterocyclic-substituted benzimidazoles

Cucurbit[n]urils (Q[n]s) are a class of supramolecular host compounds with hydrophilic carbonyl ports and hydrophobic cavities, which can selectively form host–guest inclusion complexes with guest molecules to change the properties of guest molecules. In this paper, tetramethyl cucurbit[6]uril (TMeQ[6]) was used as the host and three 2-heterocyclic substituted benzimidazole derivatives as the guests, and their modes of interaction were investigated using X-ray crystallography, 1H NMR spectrometry, and other analytical techniques. The results showed that TMeQ[6] formed a 1 : 1 host–guest inclusion complex with three guest molecules, and the binding process between them was mainly enthalpy-driven. The X-ray diffraction analysis indicated that the main driving forces for the formation of these three inclusion complexes included hydrogen bonding interactions and ion dipole interactions. There are two modes of interaction between G3 and TMeQ[6] in the liquid phase, indicating that the benzimidazole ring and heterocyclic substituents on the guest molecule compete with the cavity of TMeQ[6]. Besides, the addition of TMeQ[6] significantly enhanced the fluorescence of these guests and slightly improved their solubility.

Compared with the binding constants determined by ITC, the binding coefficients determined by UV-Vis and fluorescence titration were smaller(Table S1).It is Electronic Supplementary Material (ESI) for RSC Advances.This journal is © The Royal Society of Chemistry 2024 considered that this is due to that there are more factors affecting the experimental results in the process of UV-Vis spectroscopy and fluorescence measurement than in ITC.The ITC theoretical basis of the system was the thermal effect generated during the mixing process of host guest solutions, and the binding constant was obtained through computer processing, with higher accuracy.Although the calculation results of the binding constants of the three inclusion complexes by the three methods were not completely consistent, the larger binding constants indicated that the three benzimidazole derivatives formed stable inclusion complexes with TMeQ[6].
Subsequently, the mixture was allowed to stand at room temperature for a period of 7-14 days.This process resulted in the formation of complex 1 with a yield of 38%.
Synthesis of complex 2: TMeQ[6] (15 mg, 14.25 μmol) was dissolved in hydrochloric acid solution (5 mL, 3 mol/L ).G2 (5.0 mg, 25.84 μmol) were added to the resulting mixture.The mixture was then subjected to ultrasonic oscillation, followed by heating at 80°C for a duration of 10 minutes.Subsequently, the mixture was allowed to stand at room temperature for a period of 7-14 days.This process resulted in the formation of complex 2 with a yield of 28%.
Subsequently, the mixture was allowed to stand at room temperature for a period of 7-14 days.This process resulted in the formation of complex 3 with a yield of 35%.

1 H NMR spectroscopic analysis
The 1 H NMR titration spectra obtained for TMeQ [6] in the presence of different equivalents of G2 are displayed in Figure 1.The benzimidazole part was shielded and enters the cavity of TMeQ[6] when the molar ratio was 1⁚1, the H 1 and H 2 peaks of G2 .The proton signal presents a free peak as the G1 concentration was further raised, which was evidence that TMeQ[6] and G2 form a 1:1 host-guest inclusion complex.The 1 H NMR titration spectra obtained for TMeQ[6] in interaction with different equivalents of G3 are shown in Figure S2.All of the proton peaks of G3 were split into two groups, one of which moved to downfield and the other moved upfield, (the blue line signified mode A, whereas the red line signified mode B).This indicates that there are two modes of action between TMeQ[6] and G3.In mode A, the benzimidazole ring of G3 entered the cavity of TMeQ[6] and the phenyl group was situated at the port of TMeQ[6] when the molar ratio was 1⁚1.The H 1a and H 2a peaks of G3 were shifted upfield by 0.88 and 0.80 ppm, respectively, when compared with the free state, and H 3a and H 4a were shifted downfield by 0.37 and 0.20 ppm, respectively.However, mode B was the antithesis of mode A. H 3b and H 4b were shifted upfield by 1.32 and 0.57 ppm, respectively, when compared to the free state, while H 1b and H 2b were shifted downfield by 0.02 and 0.19 ppm, respectively.This demonstrated that TMeQ[6] and G3 form a 1⁚1 host-guest inclusion complex when the proton signal displayed a free peak as the concentration of G3 was further increased in both modes.We made several attempts to obtain better quality data for this structure however, due to twinning, disorder, poor crystal quality etc. the R int of complex 2 value is high.
This structure was included for comparison with the other similar complexes and characterized by 1 H NMR spectra.Moreover, data completeness of is 99.4% which guarantees a correct structural elucidation of complex 2. We are confident the structural characterization is valid.and there is a large amount of disorder in the structure, which caused the level B alerts.