Acyclic cucurbit[ n]uril bearing alkyl sulfate ionic groups

Abstract

We report the synthesis and characterization of a new acyclic cucurbit[n]uril (CB[n]) host C1 that features four alkyl sulfate ionic groups. The X-ray crystal structure of the C1·Me ₆ CHDA complex is reported. Host C1 is significantly less soluble in water (4 mM) compared to the analogous acyclic CB[n] host M1 which features sulfonate ionic groups (346 mM). Host C1 does not undergo significant self-association according to the results of ¹H NMR dilution experiments. The molecular recognition behavior of the hosts C1 and M1 toward a panel of seven ammonium ions was explored by ¹H NMR spectroscopy and isothermal titration calorimetry (ITC). We find that C1 generally binds slightly more tightly than M1 toward a specific guest. C1 binds more tightly to quaternary ammonium guests compared to the corresponding primary ammonium ions.

Keywords: X-ray crystallography; cucurbituril; host–guest chemistry; isothermal titration calorimetry; molecular container.

Figure 1

Chemical structures of CB[n] and selected acyclic CB[n]-type molecular containers M1 and M0.

Scheme 1

Synthesis of C1. Conditions: a) TFA/Ac₂O, 70 °C, 3.5 h, 71%; b) LiOH, 50 °C, 69%; c) dry pyridine, pyridine sulfur trioxide complex (20 equiv), 90 °C, 18 h, 68%.

Figure 2

a) ¹H NMR spectrum (600, D₂O, rt) and b) ¹³C NMR spectrum recorded (150 MHz, D₂O, rt) for C1.

Figure 3

Chemical structures of guests used in this study along with the complexation induced changes in chemical shift (Δδ) upon formation of the C1·guest complexes. Negative Δδ values represent upfield shifts upon complexation.

Figure 4

¹H NMR spectra recorded (400 MHz, D₂O, rt) for: a) Me₆PXDA (0.5 mM), b) a mixture of C1 (0.5 mM) and Me₆PXDA (1.0 mM), c) a mixture of C1 (0.5 mM) and Me₆PXDA (0.5 mM), and d) C1 (0.5 mM).

Figure 5

Cross-eyed stereoview of the C1·Me₆CHDA complex in the crystal. Color code: C, gray; H, white; N, blue; O, red; S, yellow.

Figure 6

Cross-eyed stereoview of the crystal packing observed in the molecular cell of C1·Me₆CHDA. H-atoms are omitted for clarity. N···O distances less than 4.40 Å are indicated with dashed lines. Color code: C, gray; N, blue; O, red; S, yellow.

Figure 7

a) Representative plot of DP (μcal s⁻¹) versus time from the titration of C1 (0.1 mM) in the ITC cell with a solution of CHDA (1.0 mM) from the ITC syringe. b) Plot of ΔH versus the C1:CHDA molar ratio. The solid line represents the best fit of the data to the single-set-of-sites binding model implemented in the PEAQ ITC data analysis software. The measurements were performed in triplicate and yielded K_a = (6.49 ± 0.10) × 10⁵ M⁻¹ and ΔH = −7.82 ± 0.02 kcal mol⁻¹. c) Representative plot of DP versus time from the competitive titration of C1 (0.1 mM) and CHDA (0.8 mM) in the cell with a solution of Me₆PXDA (1.0 mM) from the syringe. d) Plot of ΔH versus the C1:Me₆PXDA molar ratio. The solid line represents the best fit of the data to the competitive binding model implemented in the PEAQ ITC data analysis software. The measurements were performed in triplicate and yielded K_a = (2.47 ± 0.06) × 10⁸ M⁻¹ and ΔH = −12.43 ± 0.02 kcal mol⁻¹.