Binding and selectivity aspects of an expanded azamacrocycle for anions

Abstract

An expanded azamacrocycle L, containing four secondary and two tertiary amines was synthesized, and its binding ability towards chloride, bromide, iodide, sulfate, nitrate and perchlorate were determined by ¹H NMR titrations in D₂O at pH 1.7. The results suggest that the ligand is capable of forming a complex with each of the anions examined, showing the selectivity for sulfate in water. X-ray diffraction analysis of the perchlorate complex of L suggests that the ligand is tetraprotonated and is involved in interacting anions from both sides forming a ditopic complex with strong NH···O bonds. In the packing diagram, the macrocycles and external perchlorates are alternatively linked though hydrogen bonding to form a 1D chain.

Anion recognition studies with synthetic receptors have received significant attention in recent years because of an important role played by anions in the environment as well as in human health.¹ Polyamines, such as azamacrocycles, are typical ligands for cation binding,² which are also effective systems to bind a variety of anions in different solvents under protonated states.³ As reported earlier,^4,5 monocyclic receptors preferentially bind two anions forming ditopic complexes showing different binding modes,⁶ for example, face, bipyramidal, cross, and encapsulation in solid states. Unlike a cryptand, which provides a confined cavity for hosting an anion,^7,3d a macrocycle can interact from one or both sides of the ring. In particular, p-xylyl-based macrocycles have shown to provide two well-defined binding sites to attract anions through hydrogen bonding and electrostatic interactions. For example, a macrocycle with 26 membered ring consisting of N-methyl-2,2'-diaminodiethylamine and p-xylyl-spacers is found to complex two bromides^4b or two chlorides⁶ in the solid state. However, it formed a 1:1 complex with the anion in solution. This ligand is also useful in making a chemosensor after introducing dansyl groups, showing high affinity for H₂PO₄⁻, HSO₄⁻ and Cl⁻ in DMSO.⁸ In our continuing efforts on anion binding with artificial hosts,⁹ we synthesized an expanded macrocycle L with 30 membered ring containing N-methyl-3,3'-diaminodipropylamine, and studied its anion binding ability for halides and oxoanions. In the present work, we report ¹HNMR titration studies of the ligand showing moderate selectivity for sulfate in aqueous medium, and the crystal structure of perchlorate complex.

The ligand L was synthesized from the condensation of N-methyl-3,3'-diaminodipropylamine with teraphthaldehyde at 0ºC in CH₃OH followed by the reduction with NaBH₄ (Scheme 1).¹⁰ Perchlorate salt of L was prepared from the reaction of the neutral ligand L with aqueous HClO₄ in CH₃OH. X-ray quality crystals were grown from the salt dissolved in H₂O after 3 days by slow evaporation of solvent at room temperature.

Scheme 1.

Synthesis of L.

The ability of the ligand to bind anions was investigated by ¹H NMR titration studies using its hexatosylated salt of L in D₂O at pH 1.7. The ligand (5 mM) was titrated with a series of inorganic anions (X⁻ = Cl⁻, Br⁻, I⁻, ClO₄⁻, NO₃⁻ and SO₄²⁻) using the corresponding sodium salts (50 mM).¹¹ The addition of an anion to L resulted into an appreciable downfield shift of the ligand’s protons indicating the interactions of the ligand with the added anion. The highest shift changes were observed upon the addition of perchlorate under the similar condition. In this case the large shifts were observed for NCH₂ (b, Δδ=0.05 ppm). It is remarkable that the proton on NCH₃ (a) also shifted significantly (Δδ=0.07 ppm) indicating possible interaction of tertiary protons with sulfate. On the other hand, the aromatic protons of L are found to shift by only a small magnitude (Δδ 0.02 ppm). The similar trend was observed for other anions investigated. The observed shift change in L as a function of the anion concentration gave the best fit for a 1:1 binding model (Figure 1).¹² As listed in Table 1, the ligand showed good selectivity for sulfate over nitrate and perchlorate, exhibiting a binding trend of perchlorate < nitrate < sulfate. Under the similar condition, the ligand, however, did not show any appreciable binding for phosphate, which could be due to the pH (1.7) at which the phosphate is protonated, and incompetent of interacting with the ligand. However, as reported previously, sulfate has a lower tendency to undergo protonation and can exist as anionic species in very acidic solution pH < 2.¹³ The ligand showed weak interactions for halides due to the mismatch of the anion within the cavity. The binding trend, which correlates roughly with the electronegativity of anions, indicates that the observed binding is perhaps dominated by electrostatic interactions of the charged ligand.

Figure 1.

¹H NMR titration curves of L with different anions following the chemical shifts of NCH₃ in D₂O at pH 1.7.

Table 1.

Association constants (K) of the anion complexes determined by ¹H NMR titration at pH 1.7

Anion	K, M−1	Anion	K, M−1
Sulfate	580	Iodide	30
Perchlorate	120	Bromide	20
Nitrate	40	Chloride	15

In order to understand the solid state behavior of L with an anion, attempts were made to grow crystals with different anions, however, we are successful in isolating X-ray quality crystals for only perchlorate anion. Single-crystal X-ray diffraction analysis¹⁴ of the perchlorate crystal reveals that the salt crystallized in the triclinic space group, in which the ligand is tetraprotonated with four perchlorate anions to balance the charges. There is no solvent molecule in the structure. As shown in Figure 2, two perchlorates are bonded at the two poles of the macrocycle from both sides, in which each anion is coordinated with the cationic unit via two strong NH···O bonds (< 3 Å, see Table 2). The binding mode of the macrocycle with the two perchlorate anions can be classified as —cross binding reported earlier,⁶ and similar to that observed in the analogous bromide adduct with the macrocyle containing ethylene chains (instead of propylene chains).^3b The macrocycle and the anions lie on an inversion center in a chair conformation. The two tertiary nitrogen atoms are unprotonated, and act as hydrogen bond acceptors of symmetry related protonated NH groups (N3 and N3i), with the NH···N distance of 2.789 Å that is shorter than the van der Waals radius of two nitrogen atoms. Each of the secondary nitrogen atoms (N2, N3, N2ⁱ and N3ⁱ) is protonated and acts as three hydrogen bonds donors either for three perchlorates or two perchlorates and one unprotonated nitrogen (see, Figure 3).

Figure 2.

Crystal structure of [H₄L](ClO₄)₄ showing two perchlorates (ball and stick) bonded to the macrocycle.

Table 2.

Hydrogen bonding parameters (A, °) in perchlorate complex of L.

D—H···O	H···O	D···O	∠DHO
N2—H22N···O1	2.20	2.8335(19	125
N2—H22N···O2iii	2.23	2.9835(18)	138
N2—H21N···O5ii	1.98	2.892(2)	173
N3—H31N···O7iv	2.31	2.775(2)	111
N3—H32N···O8	1.97	2.840(2)	157
N3—H31N···N1i	1.99	2.7891(19)	144

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) x, y−1, z; (iii)−x, −y+1, −z; (iv) −x+1, −y+2, −z+1.

Figure 3.

Hydrogen bonding environment surrounding the macrocycle via NH···O contacts in [H₄L](ClO₄)₄.

Because of the presence of propylene chains, the macrocycle is less strained than that of ethylene chains, assisting the two aromatic rings closer to each other (Ar_centroid···Ar_centroid distance 4.889 as compared to 5.402 Å found in the bromide complex of the macrocycle with ethylene chains and p-xylyl-spacers^4b). The two phenyl ring planes are almost parallel, which are separated by a short distance of 3.410 Å suggesting a strong π−π stacking interactions between the two rings. This distance is shorter than that observed in the neutral ligand (4.24 Å) reported by Delgado and co-workers,¹⁵ which could be due to the intermolecular hydrogen bonding (NH···N). External perchlorates that are coordinated with the protonated nitrogen (N2 or N2ⁱ), accept four hydrogen bonds from adjacent macrocycles resulting in the formation of a 1D chain (Figure 4). The connecting macrocycles are parallel to each other and separated by 5.950 Å (N2-N2*). Extending the structure along the b axis form a 2D sheet, which is filled by anions through a hydrogen bonding network (Figure 5). In this case the perchlorate anion coordination with N3 and N3i serve as linkers of the two layers that are separated by 6.444 Å (N3-N3*).

Figure 4.

1D chain formed by perchlorates and macrocycles in [H₄L](ClO₄)₄.

Figure 5.

Packing diagram of [H₄L](ClO₄)₄ viewed along the b axis, showing filled perchlorates between the layers.

In summary, a p-xylyl based macrocycle with an expanded cavity is capable of binding anions through hydrogen bonding and electrostatic interactions at low pH in water, which is a competitive polar solvent. Although, the observed binding constants are not very strong, it exhibits a moderate selectivity for sulfate anion. The present structural characterization of the perchlorate salt indicates that the macrocycle acts as a ditopic host for complexing perchlorate anions, that are bonded with the protonated amines of L. In the solid state, strong π−π interactions between the two phenyl rings in the macrocycle, perhaps make the ligand unfavorable to accommodate an anion at the center of the cavity. However, in solution, this effect is lessened due to the strong solvation effect allowing the ligand to form a 1:1 complex with an anion. The solution studies along with structural characterization of the anion complex provide insight for the future direction of designing related ligands for the selective recognition of target anions.

Appendix A. Supplementary material

CCDC 764946 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Supplementary data associated with this article can be found, in the online version, at doi: ???.