Alkyl substituted 4-pyrrolidinopyridinium salts encapsulated in the cavity of cucurbit[10]uril

The interaction between cucuribit[10]uril (Q[10]) and a series of 4pyrrolidinopyridinium salts bearing aliphatic substituents at the pyridinium nitrogen, namely 4-(C4H8N)C5H5NRBr, where R = Et (g1), n-butyl (g2), n-pentyl (g3), n-hexyl (g4), n-octyl (g5), n-dodecyl (g6), has been studied in aqueous solution by 1H NMR spectroscopy, electronic absorption spectroscopy and mass spectrometry. The results revealed that the guests g1-g5 are located completely inside the cavity differing only in the orientation of g1, g4 and g5 which are aligned with the portal, whilst g2 and g3 are perpendicular to it. For g6, the tetrahydropyrrole moiety remains outside of the portal. DFT calculations confirm the stability of the guests in the Q[10] and the possibility of their curved structure inside the Q[10].

We are interested in the host-guest behaviour of Q[n]s, and have previously reported how Q[n] systems, where n = 6 and 8, interact with a variety of pyridinium salts. [35][36][37][38] Given the interest in 4-pyrrolidinopyridines as for example catalysts in acyl transfer reactions, [39][40][41] we have focused on our recent studies on this type of guest. In the case of Q [6], we found that for N-butyl-4-pyrrolidinopyridine, only the butyl chain was 4 found to reside in the cavity. [42] We now extend our host-guest studies to the Q [10] system (see chart 1), and report our observations on its interaction with a series of 4pyrrolidinopyridinium salts, namely 4-(C4H8N)C5H5NRBr, where R = Et (g1), n-butyl (g2), n-pentyl (g3), n-hexyl (g4), n-octyl (g5), n-dodecyl (g6), which are characterized by 1 H NMR and 13 C NMR (Figure S1-S6).

Chart 1.
Guests and Q [10] used in this study.

NMR spectroscopy
The binding interactions between each of the pyrrolidinopyridinium guests and Q [10] can be conveniently monitored using 1 H NMR spectroscopic data recorded in neutral D2O solution. Figure 1 shows the changes observed in the 1 H NMR spectrum of g1 as progressively larger amounts of Q [10]      For comparison, the chemical shifts of all the protons in these systems are presented in Table 1.

UV spectroscopy
Electronic absorption spectroscopy can be utilized to afford information about the binding mode(s) among the host and/or guest molecules, and so to further understand the binding of these 4-pyrrolidinopyridinium salts to Q [10], we employed UV-vis spectrometry herein. The UV spectra were obtained using aqueous solutions containing a fixed concentration of guest g1-g6 and 1.00 equiv. of Q [10]. As shown in Figure 5, the addition of 1.0 equiv. of Q [10] to the solution of the guest in water induces similar phenomena in the six systems. In particular, the guests 1-6 exhibited a maximum UV absorption at 282 nm in aqueous media on addition of Q [10] (1.0 equiv.) which resulted in a slight red shift, and the UV absorption intensity decreased significantly. 10 These observations indicate that the interaction between Q[10] and guest 1-6 has occurred.

Mass spectrometry
The nature of the inclusion complexes between Q[10] and the 4-pyrrolidinopyridinium guests was also established by the use of MALTI-TOF mass spectra, as shown in

DFT calculations
We conducted first-principles calculations based on density functional theory (DFT) [43,44] to obtain the binding energy and the atomic structure of the pyrrolidinopyridinium guests in Q [10]. The binding energy will confirm the observed stability of the guest inside the Q [10], while the atomic structure will show the differences in the structure of the guest. We used a supercell approach, in which the guest and the host are placed in a (24x24x24)-sized unit cell. The diameter of the model Q[10] is 12.801Å and the width is 6.215Å as shown in Figure 7(A) and Figure 7 (B), thus, the chosen unit cell size is enough to prevent interaction with periodic images. We used the projector-augmented-wave (PAW) method [45] to treat the ion-electron interaction and the Perdew-Burke-Ernzerhof functional (GGA-PBE) [46] to describe the exchange and correlation effects. Because of the presence of oxygen and carbon in the guest/host system, a large 400 eV plane wave cut-off energy is used. The molecular structure of both the guest and the host only necessitates a 1x1x1 K-point. All the DFT calculations are implemented in the Vienna Ab-initio Simulation Package (VASP). [47,48] The above calculation method and parameters are tested on pyridine and we have found a 1.343Å C-N, 1.395Å C-C and 1.091Å C-H bond lengths in agreement with experiment (1.340Å, 1.396Å, 1.086Å). [49] The obtained bond angles, which are 120.572° for ∠H-C-C , 117.047° for ∠C-N-C, 123.697° for ∠C-C-N, and 118.427° for ∠C-C-C, are also in good agreement with experiment (120.780°, 116.980°, 123.790°, 118.500°) [46] , confirming the suitability and robustness of the employed theoretical methods.
Three guests are considered namely, g1, g2 and g3 and the optimized structures are depicted in Figure 7(C)-(E). Although, three other larger guests (g4-g6) are not included in the DFT calculations due to their very large size requiring a much larger diameter and width for the host, the trends on the interaction can still be well captured. The guests are placed parallel to the center axis of the host (z-axis) and all the 205 atoms in g1/Q [10], 211atoms in g2/Q [10] and 214 atoms in g3/Q [10] are allowed to relax using the conjugate-gradient algorithm until convergence is achieved, that is, when the forces on the atoms are ~0.01eV/Å. The optimized guest/host structures are shown in Figure 8, and the binding energies (Eb) are given in Table 2. Eb is calculated with respect to the isolated guest and isolated host. We note that the binding energies are all negative, indicating stability of the guests inside the Q [10]. Because of the obvious curvature of the alkyl chains as seen on the empirical diagrams above, we obtained the N + -e-f and f-g-h angles, which can quantitatively confirm the curvature as the chains become longer. These angles are given in Table 2. We note that for all guests, N + -e-f decreases when the host encapsulates the guests. For g2 and g3, the f-g-h angle also decreases. Thus, we can see the curving of the chains towards the -y axis in Figure 8. The changes in these angles led to contraction or elongation in the N-C and C-C bonds (please see Table 2). In the case of g1, N + -e decreases. For g2 and g3, an alternating decrease-increase in the last three C-C bonds (i.e. from e-f and f-g for g2 and g3, respectively) are noted. We think that such alternating contraction and elongation of bond lengths compensates for the significant decrease in the bond angles for g2 and g3.  [10] and angles/distances between nitrogen and the carbon atoms of the alkyl chain. These atoms are depicted in Figure 8. Down (up) arrows indicate decrease (increase) with respect to that of the isolated guest molecule.

General remarks
To analyze the host−guest complexation between Q

Conclusion
In summary, we have conducted spectroscopic investigations of the interaction between Q[10] and 4-pyrrolidinopyridinium salts 4-(C4H8N)C5H5NRBr, where R = Et (g1), nbutyl (g2), n-pentyl (g3), n-hexyl (g4), n-octyl (g5), n-dodecyl (g6). Results revealed that the guests g1-g5 are located completely inside the cavity differing only in their orientation with g1, g4 and g5 aligned with the portal whilst g2 and g3 are perpendicular to it. For g6, the tetrahydropyrrole moiety remains outside of the portal. Calculations suggest that the guests are stable in the Q [10] host and that the curvature of the alkyl chain increases as the length of the chain increases.