Binding Studies on an Arene-Capped Bicyclic Cyclophane with Ï-Rich

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Binding Studies on an Arene-Capped Bicyclic Cyclophane with π‑Rich Neutral Guests and Anions Sourav Chakraborty, M. Arunachalam, Purnandhu Bose, and Pradyut Ghosh* Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, 2A & 2B Raja S. C. Mullick Road, Kolkata 700032, India S Supporting Information *

ABSTRACT: Structural aspects of binding of π-rich neutral guests with L and anions with [H6L]6+ are examined thoroughly. L forms inclusion complexes with π-rich solvents, 2DMSO⊂L (1), 3DMF⊂L2 (2), (DMF·benzene·DMF)⊂L2 (3), MeCN⊂L (4), and MeCOMe⊂L (5) in dimethylsulfoxide (DMSO), dimethyl formamide (DMF), benzene/ DMF, acetonitrile (MeCN), and acetone (MeCOMe) respectively. The single crystal X-ray structural analysis of complexes illustrates cavity and cleft binding of these guests via N− H···O interactions in 1, 2, 3, 5 and N−H···N interactions in 4 with the secondary nitrogen center of L and the hydrogen bonding acceptor atoms of the solvent guests. Inclusion of benzene in the side pocket is also observed in 3. Our efforts to isolate single crystals with solvents such as MeOH, EtOH, CHCl3, and CH2Cl2 are unsuccessful. Single crystal X-ray diffraction study has also shown the encapsulation of nitrate in the cleft of [H6L]6+ via N− H···O hydrogen bonding interactions in [H6L][NO3]6·HNO3·6H2O (6), whereas in [H6L]2[ClO4]12·CH3OH·17H2O (7) perchlorates are recognized in the cavity and side pockets of [H6L]6+. This receptor has previously shown encapsulation of iodide (8), and Cl−···H2O (9). A potentiometric study of L exhibits the maximum concentration of [H6L]6+ species at pH 2−3 in MeOH/H2O 1:1 (v/v) binary solvent. Anion binding studies with L at pH 2.0 in MeOH/H2O 1:1 (v/v) solvent system are examined by isothermal titration calorimetric (ITC) experiments.

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INTRODUCTION Polyammoniums are one of the most successful classes of receptors for binding and recognition studies of various anions in aqueous medium that are of biological and environmental importance.1,2 Although native polyamines can act as hydrogen bond donors with neutral guests, upon protonation ammonium groups act as an excellent hydrogen bond donors (recognition element) for anions. Tris(2-aminoethyl)amine (tren) derived polyammonium cryptands have been extensively studied and are popular in the anion coordination chemistry.3−6 On the other hand, limited reports are available on anion binding studies with the analogous benzene platform based polyammonium cryptands.7 In 1986, Lehn et al. developed the first example of benzene capped haxaamine cryptands with aliphatic spacers that exhibits anion binding in their protonated states.8 A second report appeared only in 2008 in which our group demonstrated the halide binding properties of an arene-capped cyclophane receptor with m-xylyl spacer, L (Figure 1) in its hexaprotonated state.7b Later, Delgado et al. explored similar cyclophanes toward various anions binding studies.7c,d However, prior to our work, in 2006 Roelens et al. reported a similar cyclophane with pyrrole spacers for recognition of carbohydrate.9 Very recently, tren and arene-capped hybrid polyamine receptors have been studied for dicarboxylate recognition.7e There are also examples of benzene capped cyclophane which act as neutral receptors for anions.10 A macrobicyclic cage has also shown encapsulation of a neutral solvent guest such as © XXXX American Chemical Society

Figure 1. Cryptand L.

DMSO in the cavity.11 A very early example of inclusion of ethanol, chloroform, and acetonitrile by macrocyclic receptors has been reported by Vö gtle et al.12 Herein we have demonstrated native polyamine L as an excellent host for a number of π-rich neutral guests by single crystal X-ray diffraction studies and its hexaprotonated form [H6L]6+ as receptor for various anions such as nitrate, perchlorate, etc. We also demonstrate the dual binding (cavity as well as cleft) property of L and [H6L]6+ with solvent molecules and anions respectively by single crystal X-ray structural analysis. Moreover, isothermal calorimetric titration studies revealed binding Received: April 20, 2013 Revised: May 23, 2013

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dx.doi.org/10.1021/cg400597e | Cryst. Growth Des. XXXX, XXX, XXX−XXX

Crystal Growth & Design

Article

slow evaporation, which resulted in a few single crystals of the respective inclusion complexes. Synthesis of [H6L][NO3]6·HNO3·6H2O, (6). Complex 6 was obtained by dissolving L (72 mg, 100 mmol) in methanol (10 mL) and upon adding 0.25 mL of HNO3. Water was added to the turbid solution which became clear upon addition of water and then it was filtered in hot condition. Single crystals suitable for X-ray crystallography were obtained upon slow evaporation at room temperature as colorless crystals. Crystals were separated out for characterization. Yield: 30 mg (42%). 1H NMR (DMSO-d6, 500 MHz, 298 K): δ 2.33 (s, 18H), 4.02 (s, 12H), 4.38 (s, 12H), 7.40 (s, 3H), 7.55−7.59 (m, 9H), 8.93 (s, 12H). 13C NMR (125 MHz): δ 17.6, 45.4, 49.4, 128.3, 130.0, 130.7, 132.7, 141.6. HRMS (ESI +) data: 464.93 [(L + H2O + 2H+ + NO3¯)/2]+2, 504.83 [(L + 2H2O + 6H+ + 4NO3−)/2]+2, 865.86 [L + H2O + 3H+ + 2NO3−]+, 932.78 [L + Na+ + 3H+ + 3NO3−]+. Elemental analysis calculated for C48H78N13O27: C, 45.42; H, 6.19; N, 14.35. Found: C, 45.39; H, 6.21; N, 14.31. Synthesis of [H6L]2[ClO4]12·CH3OH·17H2O, (7). Complex 7 was obtained by dissolving L (72 mg, 100 mmol) in methanol (10 mL) and upon adding 0.25 mL of HClO4. The turbid solution became clear upon addition of water and then it was filtered in hot condition. Single crystals suitable for X-ray crystallography were obtained upon slow evaporation at room temperature as colorless crystals within few days. Crystals were separated out for NMR measurements. Yield: 48 mg (67%). 1H NMR (DMSO-d6, 500 MHz, 298 K): δ 2.38 (s, 18H), 4.06 (s, 12H), 4.35 (s, 12H), 7.30 (s, 3H), 7.57−7.61 (m, 9H), 8.64 (s, 12H). 13C NMR (125 MHz) δ 18.0, 45.9, 49.6, 128.7, 130.1, 131.0, 133.0, 142.0. HRMS (ESI +) data: 411.31 [(L + 3H+ + ClO4−)/2]+2, 461.31 [(L + 4H+ + 2ClO4−)/2]+2, 512.29 [(L + 5H+ + 3ClO4−)/2]+2, 629.80 [(L + 7H+ + 5ClO4− + 2H2O)/2]+2, 923.61 [L + 3H+ + 2ClO4−]+, 1023.56 [L + 4H+ + 3ClO4−]+. Elemental analysis calculated for C97H170Cl12N12O66: C, 39.02; H, 5.74; N, 5.63. Found: C, 38.98; H, 5.72; N, 5.59. Potentiometric Studies. A potentiometric titration experiment was conducted at 298 K, using carbonate-free NaOH. The study was performed in a solvent mixture of H2O/MeOH (1:1 v/v) due to the low solubility of the receptor in water. The protonation constants of L were determined from titrations of a 1 × 10−3 M solution of L containing a slight excess of HNO3 or TsOH (10 × 10−3 M) in the presence of NaNO3 or NaOTs as supporting electrolyte to maintain the total ionic strength of the solution at 0.1 M. The range of accurate pH measurements was considered to be 2.5−8.0. Protonation constants were calculated with the help of the HYPERQUAD program.18 Isothermal Titration Calorimetric (ITC) Studies. All ITC binding studies were performed at 298 K. The stock solutions were prepared by weighing the sodium salts and L directly into the volumetric flask. The ITC experiments were performed in a 1:1 (v/v) methanol−water binary solvent mixture. Before the experiment was done, the pH of the binary solution was adjusted at 2.0 ± 0.1 (as read by pH electrode) by adding trifluoromethane sulfonic acid in the presence of sodium triflate salt (0.1 M). Triflic acid was chosen for protonation because of its highly negative pKa value (−14) compared to other acids. To study the anion binding property of [H6L]6+, different sodium salts of various anions (e.g., sodium bromide, sodium iodide, etc.) were used. The association constants, thermodynamic parameters (log K, ΔH, and ΔS) and the stoichiometries of the experiments were determined by using the fitting model (ligand in cell, one site model). In order to remove the effect of dilution, blank experiments were performed and deducted from the corresponding titration. The software used for ITC analysis was Origin 7.0. The upper panel of the VP-ITC output figure shows the heat pulses which were observed experimentally in each titration step with respect to time. The lower panel reports the respective time integrals translating as the heat absorbed or evolved for each aliquot and its coherence to a 1:1 binding model.

of halides and nitrate in methanol/water (1:1, v/v, binary solvent mixture) by L at pH ≈ 2.

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EXPERIMENTAL SECTION

Single Crystal X-ray Crystallographic Studies. In each case, a crystal of suitable size is collected from the mother liquor and is dipped in partone oil and then mounted on the tip of a glass fiber and cemented using epoxy resin. Intensity data for all crystals are collected using Mo Kα (λ = 0.7107 Å) radiation on a Bruker SMART APEX diffractometer equipped with a CCD area detector at 120 K. The data integration and reduction are processed with SAINT13a software. An empirical absorption correction is applied to the collected reflections with SADABS.13b The structures are solved by direct methods using SHELXTL14 and are refined on F2 by the full-matrix least-squares technique using the SHELXL-9715 program package. Graphics are generated using PLATON16 and MERCURY 2.3.17 In the case of DMSO inclusion complex 1, carbon atoms labeled C57 and C59 and nitrogen atom labeled N58 located in one of the cyclophane arms are disordered over two positions. In addition, DMSO molecule with sulfur labeled as S5 bound to the cleft is also disordered. All the disordered atoms are refined using PART command in SHELXTL during refinement. EADP command has been used for the refinement of Uiso values to be common for the two sites of the disordered atoms. Moreover, in complex 1, all the N−H protons of the cyclophane molecule are located on the electron Fourier map, and the distance has been fixed using DFIX command during structure refinement. In the DMF inclusion complex 2, oxygen atom O6 of the cavity encapsulated DMF molecule is disordered over two positions. The disordered atom is refined using the FVAR command in SHELXTL during refinement. EADP command has been used for the refinement of Uiso values to be common for the two sites of the disordered oxygen atom. In complex 2, all the N−H protons of the cyclophane molecule are located on the electron Fourier map, and the distance has been fixed using the DFIX command during structure refinement. Similarly, in complex 3, all the N−H protons of the cyclophane molecule are located on the electron Fourier map, and the distance has been fixed using the DFIX command during structure refinement. In the case of complex 4, all the N-Hs are located in the electron Fourier map and refined isotropically. In the nitrate complex 6, the benzene ring in one of the arms of the cyclophane cage is disordered over three positions. In addition, one of the cavities encapsulated NO3− with nitrogen center labeled as N7 is also disordered. The disordered atom is refined using the FVAR command in SHELXTL during refinement. All the N−H and C−H protons of the cyclophane cages have been fixed and refined isotropically. All the hydrogen atoms of the water molecules and a hydrogen atom in the nitric acid molecule are located on the electron Fourier map and refined isotropically. In the case of perchlorate complex 7, the oxygen atoms of the ClO4− with Cl atoms labeled Cl7, Cl10, Cl11, and Cl12 are disordered, and the disordered atoms are refined using the PART command in SHELXTL during refinement. SADI and DFIX commands have been used to fix the oxygen atoms of the perchlorate ions in acceptable geometries during the structure refinement. The EADP command has been used for the refinement of Uiso values to be common for the two sites of the disordered atoms. All the N−H and C−H protons of the protonated cyclophane cage are geometrically fixed and are refined isotropically. The hydrogen atoms of the water molecules have not been located in the electron Fourier map. Synthesis of Macrobicycle (L) and Solvent Inclusion Complexes 2DMSO⊂L (1), 3DMF⊂L 2 (2), (DMF·benzene·DMF)⊂L2 (3), MeCN⊂L (4), and MeCOMe⊂L (5). The macrobicycle was synthesized by our previously reported procedure.7b All inclusion complexes (1−2 and 4−5) are isolated as crystals suitable for single crystal X-ray diffraction studies in very low yield by dissolving the L in solvents such as DMSO, DMF, MeCN, and MeCOMe respectively. In the case of 3, the 3DMF⊂L2 (2) is dissolved in warm benzene which yields very few suitable single crystals after a month. For all the cases, beakers containing the solutions of L in various solvents are kept in a cool and dry place for B



Article

Table 1. Crystallographic Data of Solvent Inclusion Complexes of L parameters

2DMSO⊂L (1)

3DMF⊂L2 (2)

2DMF·benzene⊂L2 (3)

4MeCN⊂L (4)

empirical formula formula weight crystal system space group a (Å) b (Å) c (Å) α (°) β (°) γ (°) V (Å3) Z dcalc (g/cm3) crystal size diffractometer λ (Å) F(000) T (K) θ max reflns collected independent reflns parameters refined R1; wR2(I ≥ σ(I)) GOF

C52H67N6O2S2 872.24 monoclinic P2(1)/n 15.159(3) 15.881(3) 20.187(4) 90.00 101.589(3) 90.00 4760.8(17) 4 1.217 0.16*0.10*0.08 smart CCD 0.71073 1876 120 (2) 23.10 37421 6697 592 0.0976; 0.2731 1.040

C105H141N15O3 1661.33 triclinic P1̅ 13.6426(7) 16.9738(9) 21.6609(11) 76.6720(1) 76.6470(1) 73.1020(1) 4597.1(4) 2 1.200 0.20*0.08*0.06 smart CCD 0.71073 1800 100 (2) 24.84 43163 15820 1175 0.0750; 0.2373 1.062

C108H140N14O2 1666.34 triclinic P1̅ 13.5220(13) 17.1260(16) 21.666(2) 76.641(3) 76.489(3) 73.530(3) 4604.6(7) 2 1.202 0.18*0.14*0.10 smart CCD 0.71073 1804 120 (2) 18.63 28022 6977 1183 0.0617; 0.1817 1.023

C52H66N8 803.13 triclinic P1̅ 13.8582 (9) 16.7514 (11) 21.7956 (14) 75.1730(10) 75.9230(10) 70.7490(10) 4547.3(5) 4 1.173 0.6*0.20*0.12 smart CCD 0.71073 1736 100 (2) 25.00 32762 12269 1145 0.0924;0.2308 1.079

Figure 2. (a) DMSO inclusion complex of the cryptand. The picture exhibits both cavity and cleft binding of the solvent molecule. (b) DMF inclusion complex of cryptand where cavity bound DMF is stabilized via C−H···O and N−H···O interactions. The color codes are carbon: orange, purple. Oxygen: red. Nitrogen: blue. Hydrogen: dark gray, white. Sulfur: dark green. The spacefill model is shown in Supporting Information.

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RESULTS AND DISCUSSION

nature of the cavity of cyclophane cage, crystallization of L was carried out in various solvent systems such as DMSO, DMF, benzene/DMF binary solvent, MeCN, MeCOMe, EtOH, MeOH, CHCl3, and CH2Cl2. Interestingly, solvents with π-

Single Crystal X-ray Structural Studies on Host−guest

Complexes of L and Solvents with π-Bonds. To probe the C



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bonds, i.e., DMSO, DMF, MeCN, and MeCOMe, exclusively have resulted crystals suitable for single-crystal X-ray diffraction study. Thus, solvent inclusion complexes of the cyclophane are formed which include 2DMSO⊂L (1), 3DMF⊂L2 (2), (DMF·benzene·DMF)⊂L2 (3), MeCN⊂L (4), and MeCOMe⊂L (5)7b with DMSO, DMF benzene/DMF binary solvent, MeCN and MeCOMe, respectively (Table 1). On the other hand, we fail to isolate single crystals with solvents such as MeOH, EtOH, CHCl3, or CH2 Cl 2. In complex 1, L encapsulates two DMSO molecules of which one molecule resides perfectly at the center of the cavity and another DMSO molecule is located at the cleft (Figure 2a). The cavity encapsulated DMSO is bound to the receptor via N−H···O interaction with the secondary nitrogen center of L. The distances between the centroids of the apical benzene rings of L and the sulfur atom of the cavity encapsulated DMSO molecule are 3.435 Å and 4.353 Å where the apical benzene rings are 7.713 Å apart. One of the side pockets of L is bound to another DMSO molecule as a guest which is disordered over two positions and is also stabilized in the cleft via N−H···O interactions. The distances between the centroids of the benzene rings of the adjacent arms are 9.277 Å, 11.300 Å, 11.023 Å, which clearly indicate that two of the arms of L converge together to hold the DMSO molecule in the cleft as observed in the case of complex 5, MeCOMe⊂L.7b The spacefilling model of 1 shows complete encapsulation of the DMSO inside the cage (Supporting Information, Figure 5S). An earlier report by Smith et al. has shown encapsulation of one DMSO molecule inside the cavity of a macrobicyclic receptor,11 but in our case both cavity and cleft bound DMSO molecules are obtained. In the case of 2, two units of L crystallize with three molecules of DMF in triclinic P1̅ space group. Among the three molecules of DMF, two are encapsulated exactly in the middle of the cyclophane cavity, and another DMF molecule is located in between the clefts formed by the two receptor molecules (Figure 2b). The cavity encapsulated DMF is bound to the receptor via N−H···O and C−H···O interactions with the secondary nitrogen center and aryl C−H protons of L, respectively. The apical benzene rings are 7.391 Å apart, and the space-filling model shows complete encapsulation of the DMF inside the cage (Supporting Information, Figure 6S). The distances between the centroids of the apical benzene rings of L fall exactly on the nitrogen atom of DMF (cavity encapsulated DMF molecule). The oxygen atom of one of the cavity encapsulated DMF molecules is disordered over two positions (namely, O6A and O6B). These solid state structural observations are clearly supporting the nature of this cyclophane toward dual site guest recognition in the cavity and cleft as is observed in the cases of inclusion complexes 1. When the 3DMF⊂L2 (2) crystals are dissolved in a minimum amount of warm benzene, complex 3 is isolated as crystals suitable for single crystal X-ray diffraction study. The complex 3 is crystallized with one L, two DMF, and a benzene molecule (Figure 3a) in the triclinic P1̅ space group, which is isostructural with the complex 3DMF⊂L2 (2). Among the solvents, DMF molecules are encapsulated in the cavity, whereas the benzene molecule is bound to the cleft formed between the dimeric guests. The cavity encapsulated DMF guests are π-stacked between the apical benzene caps and are well stabilized in the cavity via hydrogen bonding interactions with the N−H protons of the receptor. The cleft bound DMF guest is held by weak interactions compared to cavity bound

Figure 3. (a) Complex 3 where one cleft bound DMF molecule is displaced by one benzene molecule, (b) acetonitrile inclusion (4) complex of ligand. The color codes are carbon: orange, purple. Oxygen: red. Nitrogen: blue. Hydrogen: dark gray, white. Sulfur: dark green. The spacefill model is shown in Supporting Information.

congener, and it is replaced by a benzene molecule which is more π rich than DMF. Although benzene is more π rich, it could not replace the other cavity bound DMF. This is because the polar aprotic solvent DMF is in good H-bonding network with the N−H protons in the cavity of L as well as π−π stacking interactions between the π-cloud of C−O and apical benzene platform of L (Supporting Information, Figure 7S). Further, the single crystal X-ray crystallographic analysis of crystals obtained from acetonitrile solution shows that L crystallizes as a dimer, and each of the hosts perfectly encapsulates one MeCN inside the cavity (Figure 3b). In this case, two symmetrically independent but almost identical molecules are present in the unit cell. However, both the receptors adopt different conformations in which the capping benzene rings are 7.406 Å and 7.338 Å apart along the imaginary line between the centroids of L. The average N−N distances between the nitrogen atoms of each arm are 6.096 Å and 6.093 Å, and the average N−N distances between the nitrogen atoms of the same arms are 4.885 Å and 4.941 Å respectively for both the L molecules. Two MeCN molecules are situated in between the two L molecules and are stabilized by the C−H···π and C−H···N interactions. Thus, the single crystal X-ray structural analysis illustrates the unique nature of L to form solvent inclusion complexes by engulfing solvents with π-bonds DMSO, DMF, MeCN, and MeCOMe in the cavity as well as in the clefts of the cage (side pockets). In all the complexes (except complex 4), we observe N−H···O interactions with the secondary nitrogen center of the ligand and the oxygen atom of the solvent guest. The detailed hydrogen bonding interactions of the solvent inclusion complexes are tabulated in the Supporting Information (Table 1S). Vögtle et al. have shown inclusion of chloroform in a keylock-like arrangement inside the cavity of a 30-membered D



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hexalactum host. The same group has also reported inclusion of ethanol by a onium type of host, namely, N-(3biphenylmethyl)quininium bromide.12 All these complexes are reported with different receptor molecules, but in our case L is capable of forming inclusion complexes with π-rich solvent molecules such as DMSO, DMF, and MeCN separately. From the above discussion, it is evident that the cyclophane L is capable of forming solvent inclusion complexes with various π-rich neutral guests. This receptor also has an ability to bind to anions in its hexaprotnated state in aqueous medium which is discussed in the upcoming section. Binding of Cl− and I− in its protonated state was previously reported by our group. In this article, we have studied its binding to other anions such as ClO4− and NO3− by single crystal X-ray diffraction studies and solution state binding of [H6L]6+ to different anions by isothermal titration calorimetric studies. Description of the Crystal Structure of Complex [H6L][NO3]6·HNO3·6H2O, (6). Upon protonation of L with HNO3 in methanol−water, complex 6 crystallizes in a triclinic system with P1̅ space group (Table 2). Single crystal X-ray

Figure 4. View showing the hydrogen bonding interactions of NO3− and water molecules with the receptor unit, [H6L]6+. Color codes are carbon: orange; hydrogen: gray; nitrogen: blue; oxygen: red. Nonbonding hydrogen atoms, three nitrates, nitric acid, and lattice solvents are not shown for clarity.

Å, which are comparatively higher than that of solvent inclusion complexes. This could be due to the repulsion between the positively charged ammonium functionality in cyclophane arms. One of the counterions NO3− is recognized at the cleft of the hexaammonium cage via N−H···O hydrogen bonding interactions. In addition, the water molecules are also stabilized in the clefts of the receptor L by N−H···O and O−H···O hydrogen bonding interactions. The details of the hydrogen bonding interactions among receptor, NO3− and water molecules are given in the Supporting Information (Table 2S). The encapsulated NO3− and the water molecules in the cleft of hexaprotonated [H6L]6+ unit are also involved in extensive hydrogen bonding interactions with the rest of the lattice water and NO3− and hence formed infinite hydrogen bonding network. Description of the Crystal Structure of Complex [H6L]2[ClO4]12·CH3OH·17H2O, (7). Protonation of L with HClO4 in methanol−water binary solvents yields the complex 7 as [H6L]2[ClO4]12·CH3OH·17H2O as colorless crystals. Complex 7 crystallizes in the triclinic P1̅ space group (Table 2), and the structural analysis reveals that the asymmetric unit of complex 7 includes 2 hexa-protonated L units, 12 perchlorate ions, 1 methanol, and 17 water molecules of crystallization (Figure 5). Also in the case of complex 7, the cyclophane cage is hexaprotonated and two units of [H6L]6+ encapsulate three perchlorate ions inside the cavity and clefts as shown in Figure 6. The distances between the centroids of apical benzene caps are 8.62 and 8.79 Å in both the cyclophane cages present in the asymmetric unit which are almost comparable to complex 6. The angles between the planes of the apical benzene rings are 14.31° and 15.33°, which are comparatively very high when compared to complex 6 as well as the solvent inclusion complexes of L. The average N−N distances between the nitrogen atoms of each arm are ∼6.1 Å and 6.2 Å, and the average N−N distances between the nitrogen atoms of the same arms is ∼6.3 Å. Perchlorate ions are encapsulated inside the cyclophane cage via N−H···O and C−H···O hydrogen bonding interactions with the receptor as well as trapped water molecules in the clefts (Figure 5). The hydrogen bonding interactions of the anions and water molecules with the receptor units are depicted in the Supporting Information (Table 3S). In addition, the water

Table 2. Crystallographic Data of Complexes 6 and 7 compound

nitrate complex, 6

perchlorate complex, 7

empirical formula formula weight crystal system space group a (Å) b (Å) c (Å) α (°) β (°) γ (°) V (Å3) Z dcalc (g/cm3) crystal size diffractometer λ (Å) F(000) T (K) θ max reflns collected parameters refined R1; wR2 (I ≥ σ(I)) GOF

C48H74N13O26.50 1257.20 triclinic P1̅ 12.3872(15) 15.5922(19) 16.3762(19) 97.037(2) 93.522(2) 109.287(2) 2945.4(6) 2 1.418 0.47*0.38*0.33 smart CCD 0.71073 1330 100(2) 26.50 12047 845 0.0746; 0.1925 1.058

C97H136Cl12N12O66 2951.58 triclinic P1̅ 17.20(2) 17.660(19) 22.55(3) 76.041(16) 79.935(11) 79.327(18) 6471.0(12) 2 1.515 0.10*0.10*0.12 smart CCD 0.71073 3068 120(2) 19.59 26493 1802 0.0815; 0.2693 1.068

structural analysis reveals the presence of one molecule of L, six NO3−, one molecule of HNO3 and six water molecules in the asymmetric unit. As expected, all six nitrogen atoms are protonated and complex 6 shows encapsulation of a NO3− and water molecules inside the cavity as well as in the cleft (Figure 4). One of the m-xylyl moieties of the cryptand is disordered over three positions (C42−C42A, C43−C43A, and C44− C44A). The distance between the centroids of apical benzene caps is 8.618 Å, which is more than the distance observed for the solvent inclusion complexes of L. The angle between the planes of the apical benzene rings is 3.17°, which is comparatively less when compared to the solvent inclusion complexes of L. The average N−N distances between the nitrogen atoms of each arm is ∼6.0 Å, and the average N−N distances between the nitrogen atoms of the same arm is ∼5.8 E



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Table 3. Logarithms of the Stepwise Protonation Constant for L in (1:1) Methanol/Water Binary Solvent Mixturea equilibrium +

L+H = HL+ L + 2H+ = H2L2+ L + 3H+ = H3L3+ L + 4H+ = H4L4+ L + 5H+ = H5L5+ L + 6H+ = H6L6+

−

Figure 5. View showing the hydrogen bonding interactions of ClO4 with the receptor units [H6L]6+ in the asymmetric unit. The perchlorate anions are bound to the receptor via C−H···anion and N−H···anion interactions. Color codes are carbon: orange; hydrogen: dark green; nitrogen: blue; oxygen: red; chloride: light green. Nonbonding hydrogen atoms, disordered oxygen atoms, and lattice solvents are not shown for clarity.

log βiH b

8.73(5) , 8.58(14)

equilibrium c

16.41(3)b, 16.42(9)c 23.83(6)b, 24.01(13)c 30.61(4)b, 30.78(12)c 36.37(5)b, 37.07(13)c 39.24 (excessive)b, 40.79 (excessive)c

+

L+H = HL+ HL+ + H+ = H2L2+ H2L2+ + H+ = H3L3+ H3L3+ + H+ = H4L4+ H4L4+ + H+ = H5L5+ H5L5+ + H+ = H6L6+

log KiH

L′

8.73b, 8.58c

8.70d

7.68b, 7.84c

7.86d

7.42b, 7.59c

7.21d

6.78b, 6.77c

6.55d

5.76b, 6.29c

5.97d

nd

4.99d

a Values for L′7d are included for comparison. b0.001 M ligand L, 0.010 M HNO3, 0.1 M NaNO3. c0.001 M ligand L, 0.010 M TsOH, 0.1 M NaOTs. d0.1M KOTS is used in case of L', ref 7d. Values in parentheses are the standard deviations in the last significant figures. nd refers to not determined accurately.

values are further compared with the ethyl substituted analogue of L (L′).7d It has been found that the protonation constant values for both the systems are quite similar (Table 3). The first protonation constant of L could not be calculated accurately due to precipitation of L beyond pH 7.5, as observed in the case of cryptand L′.7d Thus, the values are estimated at 8.73 and 8.58 (for NaNO3 and NaOTs supporting electrolytes respectively), assuming that the difference between the first and second protonation constants is mainly due to both statistical factors and electrostatic repulsions. Considering the above fact, we have calculated the protonation constant values in the working pH region (2.5−8.0). From this species distribution diagram, we can screen which species are generated at what pH region. It is clear from the species distribution diagram that the population of [H6L]6+ state is maximum at the pH range 2−3. Isothermal Titration Calorimetric (ITC) Studies. We have studied the binding properties of anions in 1:1 (v/v) methanol−water (pH = 2.0 ± 0.1) binary solvent mixtures in the presence of 0.1 M sodium trifluoromethane sulfonate/ trifluoromethane sulfonic acid (triflic acid) in ITC. Triflic acid is used to protonate the receptor, and the pH of the solution is adjusted at 2.0 ± 0.1 to obtain the maximum concentration of [H6L]6+ species in the solution which is evident from the potentiometric species distribution plot (Figure 7). Binding studies of halides and oxyanions are explored in this section. Among halides, we could analyze binding of Br− and I− with [H6L]6+. Unfortunately, no appreciable binding is observed for chloride. This could be due to the high hydration enthalpy of chloride and also high solvation enthalpy of sodium chloride. As pKa of HF is about 3.17, the binding study of F− is not appropriate at this lower pH range (pH = 2.0 ± 0.1). Among oxyanions, ClO4− and NO3− fit in the “one set of site” fitting model. However, a behavioral change in anion binding is observed on replacing the mononegative guests by a dinegative anionic guest SO42−. In this case, the titration curve does not fit in the “one set of site” fitting model unlike the case of monoanionic congeners. Here the fitting shows a nonsigmoidal nature which indicates existence of different thermodynamic phenomenon rather than that of binding. Sulfate has pKa of 1.99 in water which is likely to be higher in the presence of 50% methanol. Hence, protonation of sulfate occurs which leads to generation of bisulphate anion and also complicates the binding

Figure 6. View showing the encapsulation of ClO4¯ ions with the receptor units, [H6L]6+ . Color codes are carbon: orange and purple; chloride: green; nitrogen: blue; oxygen: red. Nonbonding hydrogen atoms, disordered oxygen atoms, and lattice solvents are not shown for clarity.

molecules are stabilized in the cavity and clefts of the receptor L by N−H···O and O−H···O hydrogen bonding interactions. Potentiometric Studies. The protonation constants of L are evaluated potentiometrically in the presence of both NaNO3 and NaOTs supporting electrolytes. The species distribution curves are shown in Figure 7 and the protonation constant values are tabulated in Table 3. Five protonation constants are obtained for L in the working pH region (2.5− 8.0), corresponding to the successive protonations of the secondary amines. The stepwise values are decreased steadily with increasing protonation state of the receptor due to increasing electrostatic repulsion between positive charges. The

Figure 7. Species distribution diagram for the protonation of L in the presence of (a) 0.1 M NaNO3, (b) 0.1 M NaOTs, CL = 1 × 10−3 M. F



Article

phenomenon. Similar is the case for dihydrogen phosphate which has a pKa even higher than that of sulfate. Table 4 shows Table 4. Thermodynamic Parameters Obtained from ITC Experiments anions

ΔH (kcal/mol)

TΔS (kcal/mol)

ΔG (kcal/mol)

log K

I− Br− ClO4− NO3−

−0.691 −0.280 −1.358 −0.729

2.440 3.874 1.714 3.546

−3.131 −4.154 −3.072 −4.275

2.30 3.05 2.25 3.14

all the thermodynamic parameters of the studied anions. Thus, in this solvent system we are unable to study the binding constants and thermodynamic parameters of binding for F−, H2PO4−, and SO42− due to their higher pKa values. In the cases of all the studied anions Br−, I−, ClO4−, and NO3−, invariably we find an exothermic binding which indicates the exclusive cause for binding. Halide Binding Studies. Figure 8 shows the ITC profile for the binding of Br− and I− with [H6L]6+. The ΔS values for

Figure 9. ITC based determination of (a) ClO4− [L (0.858 mM) and ClO4− (26.18 mM)], (b) NO3− [L (0.824 mM) and H2PO4− (28.16 mM)] binding to the host at 298 K. Model: one site.

exothermic nature of its binding with the host. The NO3− ion shows a positive entropic contribution of 3.546 kcal/mol. This entropy value for NO3− is higher than that of ClO4−. The binding of NO3− is also found to be an entropy driven process. The binding constant (log K) value calculated for NO3− is moderate and is higher than that of ClO4−.

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CONCLUSION Single crystal X-ray diffraction study reveals a recognition pattern of various neutral and anionic guests by L in its neutral and protonated forms respectively. Dual site recognition, i.e., cavity as well as cleft binding of guests, has been demonstrated unambiguously both for neutral and anionic guests. A solid state study shows the selectivity of L toward the inclusion of πbond containing solvent guests. Cleft bound guest exchange by another guest with more π-character has also been demonstrated. The hexaprotonated form of L exhibits anion binding in the solid and solution states. Upon a higher degree of protonation, distribution of positive charge over the receptor increases which enhances affinity toward anion assisted complex formation depending upon topology of the anions such as halides and oxyanions which is evident from ITC studies. The solution state ITC results exhibit that the [H6L]6+ receptor has a higher tendency to bind with NO3− with a moderate binding constant value in aqueous medium. Summary of the present work emphasizes a unique ability of L to form inclusion complexes with π-rich solvent molecules as a neutral receptor and anion−adduct formation in its hexaprotonated state.

Figure 8. ITC based determination of (a) I− [L (1.368 mM) and I− (23.50 mM)], (b) Br− [L (0.848 mM) and Br− (26.60 mM)] and binding to the host at 298 K. Model: one site.

both the cases are found to be positive which indicates a more disordered nature of the overall system during their binding with the host compared to that of the receptor [H6L]6+ in its solvated form. Table 4 shows that the binding of Br− and I− with [H6L]6+ is highly entropy driven. The positive value of the entropic term can be accounted by the overall release of solvent molecules as well as triflate counteranions in the system. Br− shows a relatively higher binding constant compared to that of I− which is largely contributed by the corresponding positive entropic values. Thus, this result suggests that the log K value decreases with the increase in the size of the halide from bromide to iodide. In other words, the binding affinity of halides with [H6L]6+ decreases with the decreasing charge density of the halide. Oxyanions Binding Studies. Figure 9 shows the ITC profile for the binding of ClO4− and NO3− with [H6L]6+. In the case of ClO4− binding to [H6L]6+, the entropy contribution TΔS (1.714 kcal/mol) is favorable along with the comparable negative enthalpy contribution (−1.358 kcal/mol). Despite the positive TΔS value, comparable negative enthalpy dictates the

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ASSOCIATED CONTENT

S Supporting Information *

1 H and 13C NMR and HRMS-ESI mass spectra of complexes 6 and 7, H-bonding tables of complex 1−4, 6, 7, ITC profiles of all studied anions, mercury images of solvent inclusion complexes 1−4, and thermal ellipsoid plots of complexes 1− 4, 6, and 7. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. G



Article

Notes

G.; Cañada, F. J.; Jiménez-Barbero, J.; Roelens, S. Chem.Eur. J. 2010, 16, 414−418. (10) (a) Bisson, A. P.; Lynch, V. M.; Monahan, M. -K. C.; Anslyn, E. V. Angew. Chem., Int. Ed. 1997, 36, 2340−2342. (b) Fairchild, R. M.; Holman, K. T. J. Am. Chem. Soc. 2005, 127, 16364−16365. (c) Kang, S. O.; Day, V. W.; Bowman-James, K. Org. Lett. 2008, 10, 2677−2680. (11) Deetz, M. J.; Shang, M.; Smith, B. D. J. Am. Chem. Soc. 2000, 122, 6201−6207. (12) (a) Vögtle, F.; Puff, H.; Friedrichs, E.; Müller, W. M. J. Chem. Soc., Chem. Commun. 1982, 1398−1400. (b) Worsch, D.; Vögtle, F. J. Inclusion Phenom. 1986, 4, 163−167. (c) Vögtle, F.; Berscheid, R.; Schnick, W. J. Chem. Soc., Chem. Commun. 1991, 414−416. (d) Berscheid, R.; Nieger, M.; Vögtle, F. J. Chem. Soc., Chem. Commun. 1991, 1364−1366. (13) (a) SAINT and XPREP, version 5.1; Siemens Industrial Automation Inc.: Madison, WI, 1995. (b) Sheldrick, G. M. SADABS, Empirical Absorption Correction Program; University of Göttingen: Göttingen, Germany, 1997. (14) Sheldrick, G. M. SHELXTL Reference Manual, Version 5.1; Bruker AXS: Madison, WI, 1997. (15) Sheldrick, G. M. SHELXL-97: Program for Crystal Structure Refinement; University of Göttingen: Göttingen, Germany, 1997. (16) Spek, A. L. PLATON-97; University of Utrecht: Utrecht, The Netherlands, 1997. (17) Mercury 2.3, Supplied with Cambridge Structural Database; CCDC: Cambridge, UK, 2009. (18) Gans, P.; Sabatini, A.; Vacca, A. Talanta 1996, 43, 1739−1753.

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS P.G. gratefully acknowledges the Department of Science and Technology (DST), New Delhi, India, for financial support. S.C. would like to thank IACS, Kolkata, India, for SRF. P.B. would like to thank DST, India, for funding. X-ray crystallographic studies were performed at the DST-funded National Single-Crystal X-ray Diffraction Facility at the Department of Inorganic Chemistry, IACS.

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