Exploring the mechanism of ion-pair recognition by new calix[4]pyrrole bis-phosphonate receptors: insights from quantum mechanics study

Abstract

Three diastereomeric bis-phosphonate cavitands based on an aryl extended calix[4]pyrrole can act as ion-pair receptors for alkylammonium/phosphonium chloride salts. In this contribution, the ion-pair binding mode and binding affinity were investigated using density functional theory (DFT) calculations and new nonconvalent weak interaction analysis method. One of the three receptors was chosen as the host and two guests were chosen to model quaternary phosphonium chloride salts and primary ammonium chloride salts respectively, and two types of arrangements – separated and contact – were taken into account for each guest. The binding energy suggests that contact arrangement is the favorable binding mode for this receptor and it prefers to bind primary ammonium chloride salts rather than quaternary phosphonium chloride salts both in the gas-phase and in solution, in agreement with the experiment. Moreover, geometry analysis and charge transfer based on natural bond orbital (NBO) analysis suggest that the binding modes and binding affinities of the receptor towards different ion-pairs are determined by the amount and strength of hydrogen bonds. Furthermore, nonconvalent weak interactions between the host and the guests have been explored to unravel the driving forces responsible for the ion-pair recognition. There are hydrogen bonding, van der Waals, cation–π, ion-induced dipole and charge–charge interactions in ion-pair recognition, and hydrogen bonding interactions play the dominant role in this process. This work unveils the mechanism of ion-pair recognition by new calix[4]pyrrole bis-phosphonate receptors, while opening exciting perspectives for the design of novel calix[4]pyrrole-based ion-pair receptors.

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Introduction

Molecular recognition is an important research topic in supramolecular chemistry. A large number of cation or anion receptors have been synthesized over the past several decades. However, these monotopic receptors are designed to bind a cation or an anion only. Different from the traditional simple ion receptors, ion-pair receptors are capable of binding both a cation and an anion simultaneously. They display significantly enhanced affinities for ions due to allosteric effects and enhanced electrostatic interactions between the cobound ions. Moreover, they have advantages in terms of substrate selectivity over monotopic receptors. Therefore, ion-pair receptors have potential applications in salt solubilization,^1,2 ion extraction,^3–6 and through membrane transport.^7–10 Ion-pair recognition has become an interesting field of research.^11–15

So far, research into ion-pair receptors has mainly been focused on calixpyrroles, calixarenes, crown ethers, etc. Among these, calix[4]pyrroles such as meso-octamethylcalix[4]pyrrole have been extensively studied as anion and ion-pair receptors over recent years.^13,15–17 Calix[4]pyrrole (Fig. 1A) are macrocyclic species composed of four pyrrole rings linked in the α-position via sp³-hybridized carbon atoms, and it was first reported in 1886 by Baeyer.¹⁸ In 1996, it was found to be able to bind certain anions in organic solvents by Sessler et al.¹⁹ In 2005, Moyer, Sessler, Gale and coworkers reported that calix[4]pyrrole can act as an ion-pair receptor for various cesium salts and certain organic halide salts in the solid state.²⁰

Fig. 1 Structure of meso-octamethylcalix[4]pyrrole. (A) Structural formula (B) 1,3-alternate conformation (C) cone conformation.

Calix[4]pyrrole have four typical conformations:^16,21 a 1,3-alternate structure (Fig. 1B), a partial cone structure, a 1,2-alternate structure, and a cone structure (Fig. 1C). It adopts a 1,3-alternate conformation in the absence of an added substrate. In anion (e.g. halide anion) complexes, the calix[4]pyrrole adopts the cone conformation with the anion sitting above the cone and forming four hydrogen bonds with the four pyrrole N–Hs. Then, in cone conformation, the calix[4]pyrrole provides an electron-rich cavity that serves as a receptor for cation.

A large variety of calix pyrrole derivatives have been developed to improve their properties for ion-pair recognition.^10,22–25 Most recently, Dalcanale and Ballester et al.²⁶ have reported three diastereomeric aryl-extended calix[4]pyrroles (Fig. 2A) with two phosphonate groups as bridging groups at their upper rim. The diastereoisomers differ in the relative spatial orientation of the P=O groups with respect to the aromatic cavity, namely ii (Fig. 2B), io (Fig. 2C), and oo (Fig. 2D) respectively. They can act as ion-pair receptors for alkylammonium/phosphonium (quaternary and primary) chloride salts in dichloromethane (DCM) solution and in the solid state. The ion-pair binding mode and binding affinity are strongly modulated by the spatial orientation of the P=O groups. The oo host forms the most stable complexes with quaternary alkylammonium/phosphonium chloride salts. On the contrary, the ii host binds primary alkylammonium chloride salt most tightly.

Fig. 2 Structure of bis-phosphonate cavitands based on an aryl extended calix[4]pyrrole. (A) Structural formula (B) ii (C) io (D) oo.

Generally, ion-pair receptors bind cations and anions in three different modes, defined as ion-separated (separated for short, Fig. 3A), solvent-bridged (Fig. 3B), and close-contact (contact for short, Fig. 3C), respectively.¹³ In ref. 26, the complexes of the receptor oo with the chloride salts display a separated arrangement, and those of the receptor ii display a contact arrangement.

Fig. 3 Binding modes for ion-paired complexes. (A) Ion-separated, the anion and the cation are bound relatively far from one another (B) solvent-bridged, solvent molecules bridges the gap between the anion and the cation (C) close-contact, the anion and the cation are in a direct contact receptor (yellow), cation (blue), anion (red), solvent (green).

Although the ion-pair binding modes and binding affinities of new calix[4]pyrrole bis-phosphonate receptors are obtained from experiment, the mechanism and driving forces of ion-pair recognition for the receptors are not clear. Furthermore, the reason why there are differences in ion-pair binding among these receptors also remains open to investigation.

In the present contribution, quantum mechanics (QM) calculations have been carried out to investigate the ion-pair binding behavior and mechanism of aryl-extended calix[4]pyrroles. The ii receptor was chosen as an example because there were many different types of weak interactions including hydrogen bonding between this host and the guests. Different possible geometries of the complexes for separated and contact arrangements were modelled and fully optimized. The structural property, the binding energy, and the charge transfer have been analyzed in detail. Moreover, the type and strength of nonconvalent weak interactions have been investigated to unravel the driving forces responsible for the ion-pair recognition.

Computational methods

First, the initial geometry of the ii host was taken from the published crystal structure.²⁶ Then, the chloride anion was added to construct ii:Cl complex. Last, On this basis, the guest cations were introduced to build ii:Cl:cation complexes in two types of arrangements – separated and contact. The tetramethylphosphonium chloride TMPCl (Fig. 4A) and ethylammonium chloride EAMCl (Fig. 4B) were chosen to model quaternary phosphonium chloride salt and primary ammonium chloride salt respectively. In ref. 26, octylammonium chloride OAMCl was used to represent the primary ammonium chloride salt. Although the OAMCl and EAMCl have different sizes, they both can be similarly accommodated in the binding pockets because OAM cation can direct the long alkyl chain away from the binding pockets of the receptor.

Fig. 4 Structure of alkylammonium/phosphonium chloride salts. (A) TMPCl (B) EAMCl.

The geometry of the complexes was fully optimized in the gas-phase using density functional theory (DFT) at the B3LYP/6-31G* level of theory.^27–29 Hydrogen bonding interactions play the dominant role in ii:Cl:cation complexes, and the B3LYP can give relatively reliable results for hydrogen bonding interactions.³⁰ In addition, the use of electron density to visualize noncovalent interactions, as described later on, is quite insensitive to the choice of electronic structure method used in the computations, particularly for very weak interactions. The harmonic vibrational frequencies were also calculated at the same level of theory in order to confirm whether the obtained geometries corresponded to the energetic minima. No imaginary frequency was found for any of the complexes.

To evaluate the binding energy in ion-pair recognition, the complexation reaction steps was designed, as shown in Fig. 5. It assumes that ion-pair binding involves four steps. The first step is the geometric deformation of 1,3-alternate structure to cone structure, corresponding to the deformation energy E¹_deform. The second step is the interaction of chloride anion and ii host, corresponding to the interaction energy E¹_interaction. Thus, the chloride anion binding energy, E¹_binding, can be computed from the equation as follows:

E¹_binding = E¹_deform + E¹_interaction (1)

Fig. 5 Complexation reaction steps used to evaluate the binding energy in ion-pair recognition.

The third step is the geometric deformation of ii:Cl complex and cation during complexation, corresponding to the deformation energy E²_deform. The fourth step is the interaction of cation and ii:Cl complex, corresponding to the interaction energy E²_interaction. Then, the cation binding energy, E²_binding, can be computed from the equation as follows:

E²_binding = E²_deform + E²_interaction (2)

Therefore, the sum of E¹_binding and E²_binding yields the total ion-pair binding energy E_binding. On the basis of optimized structures, the B3LYP method with 6-31++g** basis set was employed to calculate binding energy. Moreover, the basis sets superposition error (BSSE) correction was taken into account to obtain an accurate interaction energy by using the counterpoise correction method.³¹

In ref. 26, two solvents nonpolar DCM and more polar acetonitrile (ACN) were used to study ion-pair binding behavior. Both the salt and the initially formed anionic complex are fully dissociated and the cation is not significantly involved in the formation of ion-paired complexes in ACN solvent, thus only DCM solvent was considered to study solvation effects. Based on the optimized structures in the gas-phase, the self-consistent reaction field (SCRF) method was chosen to model the solvent environment. In the SCRF calculations, Tomasi's polarized continuum model (PCM)³² was employed to calculate the binding energy using B3LYP method with 6-31++g** basis set.

To investigate the charge transfer between the host and guest, the natural bond orbital (NBO)³³ analysis was implemented for the optimized structures by using the B3LYP method with 6-31++g** basis set.

To analyze and visualize the weak interactions between the host and guest, the electron density (ρ(r)) function, sin(λ₂(r))ρ(r) function (sin(λ₂(r)) means the sign of the second largest eigenvalue of electron density Hessian matrix at position r), and the reduced density gradient function were calculated. According to Yang's method,³⁴ weak interactions are characterized by low density and low reduced gradient values, and they can be located by generating gradient isosurfaces enclosing the corresponding regions of real space. The sin(λ₂(r)) is used to give the type of interaction, and its strength can be derived from the density on the weak interaction surface. On the basis of optimized structures, utilizing different colors to represent sin(λ₂(r))ρ(r) function value and map them onto RDG isosurfaces by Multiwfn 3.0³⁵ and VMD 1.9,³⁶ then not only the region of weak interaction but also the type and strength can be revealed visually.

All calculations were performed using the Gaussian 03 program.³⁷

Results and discussions

Geometry

The optimized structures of ii and ii–Cl are shown in Fig. 6, and the corresponding geometrical parameters are reported in Table 1. As expected, the calix[4]pyrrole fragment adopts a 1,3-alternate conformation in the free host, and it displays a cone conformation when binding with chloride anion through hydrogen bonds. Moreover, the distances P1⋯P2 and O1⋯O2 are shorter in ii–Cl than that in ii, showing that the benzene rings are induced to come close to the chloride anion through ion-induced dipole interactions.

Fig. 6 Side and top views of optimized structures of ii host (A) and ii–Cl complex (B).

Table 1 Selected bond distances (in Å) and bond angles (in degree) for optimized structures

Parameter	ii	ii–Cl	ii–TMPCl-1a	ii–TMPCl-1b	ii–TMPCl-2a	ii–TMPCl-2b	ii–EAMCl-1	ii–EAMCl-2
Symmetry	C 2v	C 2v	C s	C 2	C s	C 1	C s	C 1
N1–H1	1.01	1.03	1.02	1.02	1.03	1.03	1.02	1.03
N2–H2	1.01	1.03	1.02	1.02	1.03	1.03	1.02	1.03
N3–H3	1.01	1.03	1.02	1.02	1.03	1.03	1.02	1.03
N4–H4	1.01	1.03	1.02	1.02	1.03	1.03	1.02	1.03
H1⋯Cl	—	2.21	2.33	2.30	2.15	2.15	2.32	2.18
H2⋯Cl	—	2.27	2.37	2.32	2.23	2.23	2.28	2.26
H3⋯Cl	—	2.21	2.31	2.30	2.19	2.19	2.27	2.20
H4⋯Cl	—	2.27	2.37	2.32	2.23	2.23	2.28	2.24
∠N1–H1⋯Cl	—	176.62	173.18	177.89	174.17	174.19	165.26	161.54
∠N2–H2⋯Cl	—	162.10	160.77	168.71	163.88	163.86	178.73	156.85
∠N3–H3⋯Cl	—	176.62	172.72	177.89	172.30	172.35	163.65	167.65
∠N4–H4⋯Cl	—	162.10	160.77	168.71	163.88	163.87	178.73	159.40
P3⋯Cl	—	—	3.76	4.20	6.35	6.35	—	—
P1⋯P2	14.61	11.41	11.15	10.05	10.84	10.84	8.34	10.81
O1⋯O2	14.15	9.69	9.07	7.61	8.86	8.87	5.57	8.80
O1⋯Ha	—	—	2.17	2.07	—	—	—	—
O2⋯Hb	—	—	2.17	2.07	—	—	—	—
∠C1–Ha⋯O1	—	—	151.84	157.55	—	—	—	—
∠C2-Hb⋯O2	—	—	151.84	157.55	—	—	—	—
N5⋯Cl	—	—	—	—	—	—	3.06	4.26
H5⋯Cl	—	—	—	—	—	—	2.01	—
O1⋯H6	—	—	—	—	—	—	1.93	—
O2⋯H7	—	—	—	—	—	—	1.93	—
∠N5–H5⋯Cl	—	—	—	—	—	—	176.84	—
∠N5–H6⋯O1	—	—	—	—	—	—	144.16	—
∠N5–H7⋯O2	—	—	—	—	—	—	144.16	—
H5⋯N1	—	—	—	—	—	—	—	2.57
H6⋯N4	—	—	—	—	—	—	—	2.16
H7⋯N2	—	—	—	—	—	—	—	2.37
∠N5–H5⋯N1	—	—	—	—	—	—	—	116.60
∠N5–H6⋯N4	—	—	—	—	—	—	—	165.73
∠N5–H7⋯N2	—	—	—	—	—	—	—	128.54

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The optimized structures of ii–TMPCl are delineated in Fig. 7, and the corresponding geometrical parameters are given in Table 1. For contact arrangements, two kinds of complexes are found, denoted as ii–TMPCl-1a and ii–TMPCl-1b, respectively. The distances P1⋯P2 and O1⋯O2 are further shorter in ii–TMPCl compared to that in ii–Cl, especially for ii–TMPCl-1b. This can be ascribed to the formation of hydrogen bonds. Two C–H⋯O hydrogen bonds are formed between phosphonate-groups and methyl-groups in each complex, and the hydrogen bonds bring phosphonate-groups closer. Furthermore, the O⋯H distances and ∠C–H⋯O angles are shorter and larger in ii–TMPCl-1b than that in ii–TMPCl-1a respectively, suggesting that the C–H⋯O hydrogen bonds in the former are slightly stronger than that in the latter. Therefore, the distances P1⋯P2 and O1⋯O2 are shorter in ii–TMPCl-1b than that in ii–TMPCl-1a. In addition, the distances between H of pyrrole rings and Cl are larger in ii–TMPCl-1a and ii–TMPCl-1b than that in ii–Cl, showing that the chloride anion moves towards the TMP cation. This is because there are charge–charge interactions between ion-pair.

Fig. 7 Side and top views of optimized structures of the ii–TMPCl and ii–EAMCl complex. (A) ii–TMPCl-1a (B) ii–TMPCl-1b (C) ii–TMPCl-2a (D) ii–TMPCl-2b (E) ii–EAMCl-1 (F) ii–EAMCl-2.

For separated arrangements, there are also two kinds of complexes are found, denoted as ii–TMPCl-2a and ii–TMPCl-2b, respectively. Although they have different symmetries, the two structures are found to be quite similar to each other. In addition, the distances P1⋯P2 and O1⋯O2 are also shorter than that in ii–Cl just like for contact arrangements. It would appear from Table 1 that the distances between H of pyrrole rings and Cl are shorter in ii–TMPCl-2a and ii–TMPCl-2b than that in ii–Cl, showing that the chloride anion moves towards the TMP cation due to the charge–charge interactions. Therefore, the benzene rings are closer to each other to maintain ion-induced dipole interactions.

The optimized structures of ii–EAMCl are depicted in Fig. 7, and the corresponding structural data is gathered in Table 1. For contact arrangement ii–EAMCl-1, three hydrogen bonds are established, viz. N5–H5⋯Cl, N5–H6⋯O1, and N5–H7⋯O2. These hydrogen bonds cause the distances P1⋯P2 and O1⋯O2 to be the shortest ones among all the structures. In addition, there are charge–charge interactions between ion-pair can be confirmed from the larger H⋯Cl distances in ii–EAMCl-1 compared to those in ii–Cl. For separated arrangement ii–EAMCl-2, there are also three hydrogen bonds are formed, viz. N5–H5⋯N1, N5–H6⋯N4, and N5–H7⋯N2. Furthermore, the distance H6⋯N4 is the shortest and the angle ∠N5–H6⋯N4 is the largest among the three hydrogen bonds, indicating that hydrogen bond N5–H6⋯N4 is stronger than hydrogen bonds N5–H5⋯N1 and N5–H7⋯N2. In addition, these N–H⋯N hydrogen bonds are relatively weak from the geometric viewpoint. Similarly, the distances P1⋯P2 and O1⋯O2 in ii–EAMCl-2 are shorter than that in ii–Cl also can be ascribed to the ion-induced dipole interactions.

Binding energy

To investigate the binding modes and binding affinities of the receptor ii towards ion-pairs, the energies of complexation reaction steps in the gas-phase were determined, as presented in Table 2. The more negative the value of energy, the more favorable the corresponding complexation reaction step.

Table 2 Calculated complexation reaction steps energy (in kcal mol⁻¹) in ion-pair recognition in the gas-phase

Complex	E ^1deform	E ^1interaction	E ^1interaction (BSSE)	E ^1binding	E ^1binding (BSSE)
ii–Cl	11.59	−49.59	−48.57	−38.00	−36.98

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	E ^2deform	E ^2interaction	E ^2interaction (BSSE)	E ^2binding	E ^2binding (BSSE)	E binding	E binding (BSSE)
ii–TMPCl-1a	3.85	−83.60	−81.44	−79.75	−77.59	−117.75	−114.57
ii–TMPCl-1b	4.35	−84.67	−82.57	−80.32	−78.22	−118.32	−115.20
ii–TMPCl-2a	1.58	−69.28	−67.47	−67.70	−65.89	−105.70	−102.87
ii–TMPCl-2b	1.48	−69.41	−67.48	−67.93	−66.00	−105.93	−102.98
ii–EAMCl-1	9.90	−122.02	−119.98	−112.12	−110.08	−150.12	−147.06
ii–EAMCl-2	3.94	−98.11	−96.29	−94.17	−92.35	−132.17	−129.33

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The deformation energies E¹_deform and E²_deform are all positive, suggesting that these steps are both energetically unfavorable. Moreover, the E¹_deform is greater than all E²_deform, because binding chloride anion greatly changes the geometry of host ii from 1,3-alternate to cone structure. Although the deformation steps are unfavorable, the interactions like hydrogen bonding, van der Waals, cation–π, ion-induced dipole and charge–charge make favorable contribution to the total binding energy for each complex. The E²_binding and E²_binding (BSSE) are lower than E¹_binding and E¹_binding (BSSE) respectively for all the complexes, showing that binding cations plays the dominant role in ion-pair recognition from the viewpoint of energy.

Furthermore, for complexes ii–TMPCl, the binding energies of contact arrangements ii–TMPCl-1a and ii–TMPCl-1b are ca. 12 kcal mol⁻¹ lower than that of separated arrangements ii–TMPCl-2a and ii–TMPCl-2b. Similarly, for complexes ii–EAMCl, the binding energy of contact arrangement ii–EAMCl-1 is ca. 18 kcal mol⁻¹ lower than that of separated arrangement ii–EAMCl-2. This suggests that contact arrangement is the favorable binding mode for receptor ii, in agreement with the experiment. The main reason is that the two oxygen atoms of the phosphonate groups are pointing inwardly and can form C–H⋯O hydrogen bonds (for TMP) or N–H⋯O and N–H⋯Cl hydrogen bonds (for EAM) in contact arrangement. However, there is no hydrogen bond (for TMP) or only weak N–H⋯N hydrogen bonds (for EAM) in separated arrangement. Although there are other interactions such as cation–π interactions between cations and ii, the arrangements of ion-pair are determined by hydrogen bonding interactions.

The binding energies of ii–EAMCl are lower than that of ii–TMPCl, no matter whether it is contact arrangement or separated arrangement. It is suggested that ii binds primary alkylammonium/phosphonium chloride salt tighter than quaternary alkylammonium/phosphonium chloride salt. This result can also be largely explained by the hydrogen bonds. For contact arrangement, N–H⋯O and N–H⋯Cl hydrogen bonds can be formed for primary cation while there are only C–H⋯O hydrogen bonds for quaternary cation. The number of hydrogen bonds in the former are more than that in the latter, and N–H⋯O and N–H⋯Cl hydrogen bonds are stronger than C–H⋯O hydrogen bonds. For separated arrangement, three N–H⋯N hydrogen bonds can be formed for primary cation while there are no hydrogen bonds for quaternary cation.

The E²_interaction of ii–TMPCl-1b is ca. 1 kcal mol⁻¹ lower than that of ii–TMPCl-1a. This is mainly because the C–H⋯O hydrogen bonds in the former are slightly stronger than that in the latter according to geometry analysis mentioned above. Stronger hydrogen bonds can lower the binding energy greater. Therefore, ii–TMPCl-1b is more energetically favorable than ii–TMPCl-1a. In addition, ii–TMPCl-2a and ii–TMPCl-2b are quite close in binding energy. Combining with the geometrical structure, it can be concluded that cations are bound almost in the same way.

To study the solvation effects in ion-pair binding, the binding energies were calculated in the DCM solvent and presented in Table 3. In DCM solvent, the ion-pair binding behavior of ii is similar to that in the gas-phase. Contact arrangement is the favorable binding mode and it prefers to bind primary ammonium chloride salts rather than quaternary phosphonium chloride salts. However, the binding energies sharply increase compared with those in the gas-phase.

Table 3 Calculated complexation reaction steps energy (in kcal mol⁻¹) and experimental association constant value K_a,exp (in M⁻¹) in ion-pair recognition in the DCM solvent

Complex	E ^1deform	E ^1interaction	E ^1binding
ii–Cl	6.09	−13.52	−7.43

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Complex	E ^2deform	E ^2interaction	E ^2binding	E binding	K a,exp
					^1H NMR titration experiments	Isothermal titration calorimetry (ITC) experiments
ii–TMPCl-1a	−0.42	−10.56	−10.98	−18.41	> 10^4	2 ± 0.5 × 10^5
ii–TMPCl-1b	−0.42	−10.88	−11.30	−18.73
ii–TMPCl-2a	−0.06	−6.29	−6.35	−13.78
ii–TMPCl-2b	−0.11	−6.45	−6.56	−13.99
ii–EAMCl-1	5.00	−32.18	−27.18	−34.61	> 10^4	—
ii–EAMCl-2	2.23	−16.49	−14.26	−21.69

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Charge transfer

Hydrogen bonds are formed due to charge transfer from the proton acceptor to proton donor, and hence the amount of charge transfer plays a significant role in hydrogen bonds. Although the change in population is small, these values are chemically significant. A charge transfer of merely 0.001 e corresponds to the change of 0.627 kcal mol⁻¹ in stabilization energy.³³ To study the hydrogen bonding interactions in ion-pair recognition, the charge transfer between the ii host and ion-pair in complexes based on NBO analysis is reported in Table 4. For ii–Cl, electron transfer from chloride anion to the ii host, due to the N–H⋯Cl hydrogen bonding interactions.

Table 4 NBO charges of ions and ii in complexes and dipole moments (in Debye) of complexes

	ii–Cl	ii–TMPCl-1a	ii–TMPCl-1b	ii–TMPCl-2a	ii–TMPCl-2b	ii–EAMCl-1	ii–EAMCl-2
Cl	−0.759	−0.825	−0.819	−0.726	−0.726	−0.753	−0.740
TMP	—	0.947	0.957	0.964	0.964	—	—
EAM	—	—	—	—	—	0.859	0.937
ii	−0.241	−0.122	−0.138	−0.238	−0.238	−0.106	−0.197
Dipole moment	1.629	12.966	15.656	17.003	16.997	12.391	9.472

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For ii–TMPCl-1a and ii–TMPCl-1b, the charges of ii and chloride anion are less and more negative than that in ii–Cl respectively, and TMP cations accept electron. This observation can be interpreted in the following way. The electron transfer from ii to the TMP through C–H⋯O hydrogen bonding interactions when binding this cation. The hydrogen bonds bring benzene rings of ii closer, and then some electron transfer from benzene rings of ii to the chloride anion due to the enhanced ion-induced dipole interactions. For ii–TMPCl-2a and ii–TMPCl-2b, the electron keep on transferring from chloride anion to the pyrrole rings of ii through N–H⋯Cl hydrogen bonding interactions when binding the cation, and then equal electron transfer from pyrrole rings of ii to TMP through cation–π interactions. Therefore, ii can be taken as the media of charge transfer between ion-pair for separated arrangements.

For ii–EAMCl-1, the electron transfer from ii and chloride anion to EAM through N–H⋯O and N–H⋯Cl hydrogen bonding interactions when binding this cation. Moreover, the change of charge for cation in this complex is larger than that in other complexes, indicating that the hydrogen bonding interactions between ii–Cl and EAM are strong. For ii–EAMCl-2, on the one hand, the electron transfer from the pyrrole rings of ii to EAM through N–H⋯N hydrogen bonding and cation–π interactions. On the other hand, the electron transfer from chloride anion to EAM through media ii.

In summary, there is more charge transfer for contact arrangements than that for separated arrangements when binding cations. Furthermore, the change of charge for cation in primary alkylammonium chloride salt complexes is larger than that in quaternary phosphonium chloride salt complexes. This can be ascribed to the amount and strength of hydrogen bonds as mentioned in the energy analysis. Therefore, it is also indicated that contact arrangement is the favorable binding mode for ii and it prefers to bind primary ammonium chloride salts, in agreement with the energy analysis.

In addition, the dipole moments of complexes are also given in Table 4. As expected, the dipole moments of ion-pair complexes increase dramatically after binding cations compared with that of ii–Cl. For ii–TMPCl, the dipole moments of separated arrangements complexes are larger than that of contact arrangements complexes. This means that the centers of positive and negative charge are farther apart in the former than they are in the latter. However, on the contrary, for ii–EAMCl, the centers of positive and negative charge are farther apart in the contact arrangements complex than they are in the separated arrangements complex.

Weak interaction

To investigate the weak interaction visually, the gradient isosurfaces of RDG for host and complexes were drawn in Fig. 8–10. The surfaces are colored on a blue–green–red scale according to values of sin(λ₂(r))ρ(r), ranging from −0.04 to 0.02 au. Blue indicates strong attractive interactions (such as hydrogen bonds), red indicates strong repulsive interactions (such as steric clashes), and green indicates weak attractive interactions (such as dispersive-like van der Waals).

Fig. 8 Side and top views of gradient isosurfaces (RDG = 0.5 au) for ii (A) and ii–Cl (B).

Fig. 9 Gradient isosurfaces (RDG = 0.5 au) for ii–TMPCl-1a (A), ii–TMPCl-1b (B), ii–TMPCl-2a (C) and ii–TMPCl-2b (D).

Fig. 10 Gradient isosurfaces (RDG = 0.5 au) for ii–EAMCl-1 (A) and ii–EAMCl-2 (B).

There is steric repulsion (orange regions of the isosurface) between each pyrrole ring and its neighboring benzene rings and pyrrole rings in ii host (Fig. 8A). Therefore, energy barrier for conformational transition from 1,3-alternate conformation to cone conformation needs to be overcome. For ii–Cl complex (Fig. 8B), N–H⋯Cl hydrogen bonding interactions can be clearly detected (light blue regions of the isosurface). In addition, there are also ion-induced dipole interactions (green regions of the isosurface) between the chloride anion and four benzene rings.

The gradient isosurfaces of ion-pair complexes are shown in Fig. 9 and 10. For ii–TMPCl-1a (Fig. 9A) and ii–TMPCl-1b (Fig. 9B), two weak C–H⋯O hydrogen bonds between methyls of TMP and phosphonate groups of ii can be identified for each complex. In addition, there are cation–π interactions between TMP and benzene rings of ii. Moreover, van der Waals interactions between TMP and chloride anion can also be revealed. It should be noted that there are charge–charge interactions between TMP cation and chloride anion. However, these interactions can not be displayed in gradient isosurfaces because this method is only applied for investigating weak interactions. For ii–TMPCl-2a and ii–TMPCl-2b, the cation–π interactions between TMP and pyrrole rings of ii can be detected from Fig. 9C and D respectively. Due to the large distance between TMP cation and chloride anion, there is no van der Waals interactions between them. Additionally, the charge–charge interactions between cations and anions for separated arrangement are weaker than those for contact arrangement, because the distances between cations and anions are larger in the former than those in the latter.

For ii–EAMCl-1 (Fig. 10A), strong N–H⋯O and N–H⋯Cl hydrogen bonds between EAM and ii can be identified. In addition, there are cation–π interactions between methylene of EAM and benzene rings of ii. For ii–EAMCl-2 (Fig. 10B), three N–H⋯N hydrogen bonds can be detected, and hydrogen bond N5–H6⋯N4 is stronger than hydrogen bonds N5–H5⋯N1 and N5–H7⋯N2, in agreement with the geometry analysis. Additionally, there are cation–π interactions between EAM and pyrrole rings of ii.

Conclusions

The mechanism of ion-pair recognition by new calix[4]pyrrole bis-phosphonate receptors has been explored. The calculated binding energy of the recognition suggests that contact arrangement is the favorable binding mode for receptor ii and it prefers to bind primary alkylammonium/phosphonium chloride salt rather than quaternary alkylammonium/phosphonium chloride salts both in the gas-phase and in solution, in agreement with the experiment. Intuitive explanation can be provided by the geometry analysis and the weak interaction analysis. More or stronger hydrogen bonds between ii and cations can be formed in contact arrangement than that in separated arrangement, which favors the cation binding. Moreover, the charge–charge interactions between cations and anions in the former are stronger than that in the latter. On the other hand, the binding affinities of the receptor ii towards different ion-pairs are also determined by the amount and strength of hydrogen bonds. Furthermore, NBO analysis indicates that there is more charge transfer for contact arrangements than that for separated arrangements when binding the cation, and the change of charge for cation in primary alkylammonium chloride salt complexes is larger than that in quaternary phosphonium chloride salt complexes. This can be explained by the amount and strength of hydrogen bonds. Therefore, it is also suggested that contact arrangement and primary ammonium chloride salt are the favorable binding mode and binding guest for ii respectively.

In addition, cation–π interactions between cations and benzene rings or pyrrole rings of host are also play important roles in binding cations. In summary, there are hydrogen bonding, van der Waals, cation–π, ion-induced dipole and charge–charge interactions in ion-pair recognition. Among them, hydrogen bonding interactions largely dictates the ion-pair binding mode and binding affinity.

The main driving force responsible for the ion-pair recognition by new calix[4]pyrrole bis-phosphonate receptors has been revealed at the electronic level, providing valuable insights for designing and synthesizing stronger and more efficient calix[4]pyrrole-based ion-pair receptors. To better understand the effect of spatial orientation of the P=O groups on the ion-pair recognition, further investigation on the interactions between the other two diastereoisomeric receptors (io and oo) and ion-pairs is still needed, which is beyond the scope of this study. Furthermore, other DFT-functionals with dispersion corrections such as DFT-D3,^38–40 M06/M06-2X,^41,42 and ωB97X-D^43,44 may give accurate results in describing noncovalent interactions. Therefore, additional studies of the mechanism of ion-pair recognition with different DFT functionals are also needed.

Acknowledgements

This study was supported by the Taishan Medical University (no. 2012GCC07), Research Award Fund for Outstanding Middle-Aged and Young Scientists of Shandong Province, China (no. BS2013YY061 and no. BS2010CL045), and the Natural Sciences Foundation of Shandong Province, China (no. ZR2012CL01 and no. ZR2011BL016).

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