Molecular Recognition of Perchlorate Anion With a Cryptand-Based Synthetic Receptor

Abstract

Perchlorate anion is a highly toxic environmental contaminant, which is implicated in various health related problems. This paper reports a cryptand-based synthetic molecule (L) prepared from the reaction of tris (2-aminoethyl) amine and 2,5-thiophenedicarboxaldehyde under a high dilution condition, providing a well-defined cavity for a guest species. The hexaprotonated receptor [H₆L]⁶⁺ has been obtained from the addition of six equivalents of tosylic acid to L, which has been studied for perchlorate anion by proton NMR studies in water. The results demonstrate that the receptor strongly binds the negatively charged perchlorate via hydrogen bonding and electrostatic interactions in solution forming a supramolecular anion complex. This molecule can be useful for the future application in the environmental remediation of toxic perchlorate anion.

1.0 Introduction

Anion recognition with synthetic molecules is one of the frontier research areas mainly due to the pivotal role played by anions in diverse areas of chemistry, biology and environment (Bianchi, et al., 1997, Gale and Gunnlaugsson, 2010). Selective recognition has important applications in anion transport, control of molecular motion and sensing of toxic anions. In particular, perchlorate anion is a known environmental contaminant and is associated with various applications in aerospace industry, fireworks and automobile airbag (USEPA, 2002). Perchlorate is also associated with many health related problems; for instance, it causes the disruption of normal thyroid functions, if consumed in excess than the recommended limit (Wolff, 1998). According to the US Environmental Protection Agency, the maximum allowable limit of perchlorate in drinking water is 15 μgL⁻¹ (USEPA, 2008). However, suitable devices for detecting and binding of perchlorate in water is rare (Saeed, 2010).

During last two decades, a significant effort was made in binding of a variety of inorganic anions by synthetic receptors (Bowman-James, 2011, Custelcean, 2013, Hossain, 2009,); however, reports on the perchlorate binding with macrocyclic hosts are quite limited (Saeed et al., 2010). This is due to the weak affinity of this anion to a receptor; resulting from the low charge to radius ratio as predicted from the single charge shared with four oxygens in a perchlorate anion. Therefore from the view of both a fundamental and technological aspect, it is crucial to develop new systems that can effectively bind and remove this toxic anion particularly from water. In this work, we have chosen a thiophene-based cryptand which was previously shown to bind chloride and nitrate. In particular, the thiophene groups used as spacers in the cryptand can serve as electron-withdrawing groups, thereby providing strong electrostatic potential within the cavity in order to attract an anion. This assumption was further supported by the electrostatic potential surfaces of L calculated at the M06-2X/6-31G(d,p) level of theory, showing the highest electron density on thiophene groups (Figure 1). Herein, we report the synthesis of the cryptand L and its binding studies for perchlorate using ¹H NMR titrations in water.

Figure 1.

The ligand L, [H₆L]⁶⁺ and the electrostatic potential map of [H₆L]⁶⁺ (red = negative potential, blue = positive potential).

2.0 Experimental Section

2.1 General

The chemicals used for this work were purchased from either Aldrich or TCI America as reagent grades and used as received. Nuclear magnetic resonance (NMR) spectra were recorded at 25° C on a Varian Unity INOVA 500 FT-NMR. Chemical shifts for NMR were expressed in parts per million (ppm), and calibrated against tetramethylsilane (TMS) or sodium salt of 3-(trimethylsilyl) propionic-2,2,3,3-d₄ acid (TSP) as an external reference used in a sealed capillary tube. All NMR data were processed and analyzed with MestReNova Version 6.1.1-6384. Mass spectral data were obtained at ESI-MS positive mode on a FINNIGAN LCQDUO. Elemental analysis was done from Columbia Analytical Service (Tucson, AZ).

2.2 Synthesis

L. The synthesis of L was carried out from the reaction of tris (2-aminoethyl) amine (0.948 g, 6.48 mmol in 250 mL CH₃OH) and 2,5-thiophenedicarboxaldehyde (1.364 g, 9.73 mmol in 250 mL CH₃OH) under high dilution conditions in CH₃OH (300 mL), followed by diborane reduction, as reported earlier (Saeed et al., 2009). Yield: 76% (1.520 g, 2.46 mmol). ¹H NMR (500 MHz, CDCl₃, TMS): δ 6.64 (s, 6H, ArH), 3.85 (s, 12H, ArCH₂), 2.717 (t, 12H, NCH₂CH₂), 2.60 (t, 12H, NCH₂CH₂), 1.91 (b, 6H, NH). ¹³C NMR (125 MHz, CDCl₃, TMS): δ 142.1 (CAr), 124.31 (HCAr), 54.5 (NCH₂CH₂), 48.8 (ArCH₂) 47.6 (NCH₂CH₂). Anal. Calcd. for (C₃₀H₄₅N₈S₃): C, 58.40; H, 7.84; N, 18.16. Found: C, 58.46; H, 7.85; N, 18.17.

[H₆L]·(TsO)₆. The protonated ligand was prepared by reacting L (120 mg, 0.192 mmol) with 6-fold p-toluenesulfonic acid in methanol (5 mL). The addition of diethyl ether resulted in a white microcrystalline product that was filtered and washed by diethyl ether. The hexaprotonated form of the ligand was confirmed by ¹H NMR, ¹³C NMR and elemental analysis. Yield: 40%. ¹H NMR (500 MHz, D₂O, TSP): d 7.69 (d, 12H, TsCH), 7.35 (d, 12H, TsCH), 7.02 (s, 6H, ArH), 4.24 (s, 12H, ArCH₂), 3.06 (t, 12H, NCH₂CH₂), 2.71 (t, 12H, NCH₂CH₂), 2.38 (s, 18H, TsCH₃). ¹³C NMR (125 MHz, CDCl₃, TMS): δ 145.4 (CAr_Ts), 142.29 (CAr_Ts), 138.3 (CAr), 133.47 (HCAr), 132.4 (HCAr_Ts), 128.24 (HCAr_Ts), 53.3 (NCH₂CH₂), 48.3 (ArCH₂), 47.6 (NCH₂CH₂), 23.38 (CH₃). Anal. Calcd. for (C₇₂H₉₀N₈S₉O₁₈): C, 52.60; H, 5.52; N, 6.82. Found: C, 52.55; H, 5.54; N, 6.82.

2.3 NMR Titration Studies

Binding constants were obtained by ¹H NMR (500 MHz Varian) titrations of H₆L·6Ts with perchlorate (ClO₄¯) using sodium perchloarate (NaClO₄) in D₂O. ¹H NMR titrations were performed at pD = 2.0. The pD of the solution was adjusted with a concentrated solution of TsOH and NaOD. Initial concentrations were [ligand]₀ = 2 mM, and [perchlorate]₀ = 20 mM. Sodium salt of 3-(trimethylsilyl) propionic-2,2,3,3,-d₄ acid (TSP) in D₂O was used as an external reference in a sealed capillary tube. The titration was performed by 15 measurements at room temperature. The association constant (K) was calculated by fitting of NMR signals with a 1:1 association model using Sigma Plot (Schneider et al., 1988). Error limit in K was less that 10% which was based on the standard deviation from three titrations for each anion.

3.0 Results and Discussion

The hexaprotonated H₆L·6Ts was highly soluble in water allowing us to study the binding interaction in this polar solvent. The binding affinity of L for perchlorate anion were evaluated by ¹H NMR titration studies in D₂O at pH 2.0. The addition of sodium perchlorate (NaClO₄) to H₆L·6Ts, resulted in a significant downfield shift of the NCH₂CH₂ adjacent to secondary amines (Figure 2). Other protons were also shifted but to a lesser extent. Such a change in the proton NMR resonances is suggestive of the participation of protons on ammonium groups in hydrogen bonding with the added anion. Figure 2 shows the stacking of partial ¹H NMR titration spectra obtained from the portion-wise additions of perchlorate salt, displaying a gradual shift change in the aliphatic protons. The changes in the chemical shift of NCH₂CH₂ were plotted with an increasing amount of perchlorate at room temperature, giving the best fit for a 1:1 binding model for each anion (Figure 3). The 1:1 stoichiometry in solution was further verified by a Job plot analysis, displaying a maximum at an equimolar ratio of the ligand and anion. The binding constant was calculated from non-linear regression analysis of the change of chemical shifts, showing strong affinity of the receptor for perchlorate (K = 28,500 M⁻¹) in water. This binding constant is significantly higher than that reported in the literature for simple monocyclic systems (Saeed, et al., 2010). Clearly, the high binding of the perchlorate to [H₆L]⁶⁺ is due to the increased dimensionailty (monocyclic to bicyclic) of the cryptand used in this study, providing a suitable space for the interacting the anion inside the three-dimensional cavity via multiple hydrogen bonds as shown in Figure 4. Furthermore, the positive charges on secondary nitrogen atoms of H₆L·6Ts provide strong positive electrostatic potential for the attraction of negatively charged anion inside the cavity.

Figure 2.

¹H NMR titration of H₆L(Ts)₆ (2 mM) with an increasing amount of NaClO₄ (R = [Na ClO₄]₀/[L]₀)in D₂O at pH = 2.0.

Figure 3.

¹H NMR titration curve for perchlorate binding with H₆L(Ts)₆ in D₂O at pH = 2.0.

Figure 4.

Encapsulation of perchlorate anion by [H₆L]⁶⁺ showing hydrogen bonding interactions.

4.0 Conclusions

The results from the solution studies suggest that the ligand serves as an effective host for perchlorate in water at certain pH. The receptor molecule provides a three-dimensional cavity surrounded by multiple positive binding sites, thereby it provides an ideal environment to host the negatively charged perchlorate inside the cavity and forms an inclusion complex. The strong interaction between the host and the guest is due to the complementarity between the host and guest species in terms of sizes and charges. Both hydrogen bonding and electrostatic interactions play a significant role in stabilizing the perchlorate complex described in this paper. Such a molecular receptor holds promise for the design of selective anion sensor for environmental remediation of toxic and radioactive anions for future applications.