Study of β-Cyclodextrin–Pyromellitic Diimide Complexation

Article pubs.acs.org/JPCC

Study of β‑Cyclodextrin−Pyromellitic Diimide Complexation. Conformational Analysis of Binary and Ternary Complex Structures by Induced Circular Dichroism and 2D NMR Spectroscopies Retheesh Krishnan, Arikkottira M. Rakhi, and Karical R. Gopidas* Photosciences and Photonics Section, Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST) Trivandrum 695 019, India S Supporting Information *

ABSTRACT: Complexation of N-alkyl derivatives of PMDI with β-CD is probed using a variety of techniques. Although MALDI-TOF and CV experiments suggested complex formation, it is very evident from UV−vis and NMR experiments that these complexes are different from regular inclusion complexes. A clear understanding of the structure of the binary complex PMDI@β-CD could be obtained using ICD and NMR ROESY experiments. ICD signals were negative which suggest that the PMDI moiety is placed outside of the cavity. ROESY experiments provide support for this contention. When the alkyl group is tbutyl or 2-propyl, the CH3 protons exist very close to the inner protons of β-CD, but the aromatic proton of PMDI is clearly outside the β-CD cavity. Based on these results we proposed a structure for PMDI@β-CD with the PMDI moiety placed at the narrow rim of β-CD and the N-alkyl group projecting into the cavity and designated these as “rim-binding” complexes. Additional experiments showed that β-CD can accommodate a PMDI moiety at the narrow rim and an adamantane moiety in its cavity simultaneously, resulting in the formation of ternary complexes PMDI⊃β-CD⊂ADA. Structure of the ternary complex was also probed by ROESY. The ternary complex formation can be utilized for the design of higher order functional materials such as CDbased hydrogels. β-CD cone and arrangement of C-3, C-4, C-5, and C-6 carbons and hydrogens in the CD. The structures of native cyclodextrins are stable due to hydrogen bonding between the 2-OH and 3-OH groups of adjacent glucose units, forming a secondary hydrogen bond belt. This effect reaches its maximum in β-CD as the secondary belt formed is complete and without distortion. The width of the CD cavity is defined by the polygon formed from O-4 atoms. The radius of the O-4 polygon in the case of β-CD is around 5.0 Å.11 The most important attribute of CDs is their ability to form complexes with small organic molecules. In aqueous solutions the CD cavities are occupied by water molecules. When small hydrophobic molecules are added they tend to occupy the cavity by displacing the water molecules thereby leading to the formation of CD complexes.12,13 Almost all applications of

1. INTRODUCTION Cyclodextrins (CDs) and their complexes have played a very important role in the development of supramolecular chemistry.1−7 CDs are a family of three well-known major and many rare minor cyclic oligosaccharides containing varying numbers of D-glucopyranose units linked by α-(1,4) linkages. The three major CDs namely α, β, and γ CDs with 6, 7, and 8 glucopyranose units, respectively, are crystalline, homogeneous, and nonhygroscopic solids.1 These are shaped like truncated cones with the primary hydroxyl groups arranged on the narrow rim of the cone and secondary hydroxyl groups assembled on the wider rim.8,9 Between the wider and narrow rims is a cavity which can accommodate small hydrophobic molecules as guests and the importance of CDs in supramolecular chemistry can be attributed to their propensity for guest encapsulation in these cavities leading to the formation of host−guest complexes.10 The CD cavity is hydrophobic in nature because it is lined with the H-3 and H-5 hydrogen atoms and the O-4 oxygen atom of the glucose units. Figure 1 shows a schematic representation of © 2012 American Chemical Society

Received: October 3, 2012 Revised: November 5, 2012 Published: November 5, 2012 25004

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on CD systems and most of these papers deal with studies of inclusion complexes19 leading to the common belief that all CD complexes are inclusion complexes. In two recent communications we reported that β-CD can form noninclusion type complexes with N-alkyl derivatives of pyromellitic diimide (PMDI, see Figure 1 for structure).20,21 We categorized this interaction as “rim-binding” and proposed that in these rim-binding complexes the PMDIs lie just outside of the narrow rim of β-CD with the N-alkyl substituents inserted into the cavity through the narrow rim. In this conformation the complex is stabilized most probably by hydrogen bonding interactions between two of the PMDI carbonyl groups with primary hydroxyl groups of the CD and hydrophobic interaction between the cavity interior and the Nalkyl substituent. We also showed that PMDIs can form true inclusion complexes with β-CD if the narrow rim is blocked by substitution with a relatively large molecule such as anthracene.22 In order to have a clear understanding of the phenomenon of rim binding a study in structural terms was thought to be relevant. In this contribution we try to unveil the nature of the PMDI−β-CD interactions using a variety of techniques such as UV−visible spectroscopy, induced circular dichroism (ICD), cyclic voltammetry (CV), isothermal titration calorimetry (ITC), MALDI-TOF mass spectrometry, and 1D and 2D NMR spectroscopies. The studies were undertaken to understand precisely the mode of binding between PMDI and β-CD and the conformation of the resulting complex. Structures (and abbreviations) of the PMDI derivatives employed in this study along with their molecular dimensions are given in Figure 1.

Figure 1. Schematic of β-CD cone and structures of PMDI derivatives used in this study.

CDs, either in research or in industry, are related to complex formation.14 In most of the CD complexes, the guest molecules are either completely or partially encapsulated into the CD cavity and hence these are termed “inclusion complexes”. The most important driving force for inclusion complex formation is hydrophobic interaction, the magnitude of which is determined by the average hydrophobic surface area of the guest.12,15 The inclusion process also involve weak interactions such as hydrogen bonding, electrostatic interactions, van der Waals forces, etc.16−18 More than a thousand papers appear every year

2. EXPERIMENTAL SECTION 2.1. General Techniques. The electronic absorption spectra were recorded using a Shimadzu UV-3101 UV−vis NIR spectrophotometer. ICD spectra were obtained on a JASCO-J-815 circular dichroism spectropolarimeter. Electrochemical experiments were performed using a BAS 50W voltammetric analyzer. Solutions for analysis (10−3 M) in deionized water containing 0.1 M potassium nitrate were

Figure 2. MALDI-TOF spectrum of complex of n-BuPMDI@β−CD. 25005

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thoroughly deaerated for about an hour and then used for the CV and square wave voltammetric analysis. MALDI-TOF mass spectrometry was conducted on an AXIMA-CFR-plus instrument with 2, 5-Dihydroxy benzoic acid as the matrix. ITC data were obtained from microcal iTC 200. The raw data obtained were fitted and analyzed using origin 7.0 software provided along with the instrument. In all experiments the β-CD was taken in the cell and titrated using different PMDI solutions taken in the syringe. All NMR data were recorded in D2O purchased from Aldrich, using a 500 MHz Bruker Avance DPX spectrometer. Conditions for ROESY experiments were as follows: relaxation delay 0 s, mixing time 300 ms, spectral width 10 ppm with 2048 complex points in f 2; 256 t1 values and 4 scans per t1 value. For 2D experiments PMDIs (2.0 × 10−2 M) and β-CD (2.0 × 10−2 M) were dissolved in D2O (0.5 mL). 2.2. Materials. β-CD purchased from Aldrich was used as such. The solvents and reagents were dried and purified by standard methods prior to use. Synthesis of all PMDI derivatives were reported by us earlier.20−22

Figure 4. 1H NMR titration spectra of t-Bu-PMDI (1.1 × 10−2 M) in the absence (A) and presence (B−D) of β-CD. [β-CD] ranged from 0.36 to 1.0 equiv. Right panel shows the shift of t-Bu protons.

3. RESULTS AND DISCUSSIONS 3.1. MALDI-TOF Mass Spectrometric Studies. Figure 2 shows the MALTI-TOF spectra of a 1:1 solution of β-CD and n-BuPMDI. The peak at m/z 1514 corresponds to 1:1 complex of β-CD and n-BuPMDI. Other PMDI derivative also complexed with β-CD as evident from the MALDI-TOF spectra (SI, Figures S1 and S2, in all cases mass peaks correspond to PMDI + β-CD − counteranion). This result indicated that, in PMDI solutions containing β-CD, a 1:1 complex of the two exists. In this report we designate these complexes as PMDI@β-CD. 3.2. UV−Visible Studies. Interaction of small molecules with CDs often leads to changes in the absorption spectra of the molecules.23,24 The changes in the absorption spectra can be used to obtain the equilibrium association constants.25 In the case of the PMDI derivatives studied here, the absorption spectra indicated only minor changes in the presence of β-CD, as shown in Figure 3 (absorption spectral profiles for other

only very small changes in the presence of β-CD. The t-butyl group experienced a downfield shift of 0.09 ppm along with slight broadening. It is to be noted that the PMDI aromatic proton which appears as a singlet around δ = 8.21 ppm remains nearly unchanged suggesting that the PMDI chromophore is residing most probably outside of the β-CD cavity in the PMDI@β-CD complex. We have reported similar results for the other two PMDI derivatives in the earlier study.20 The presence of guest molecules within the CD cavity leads to considerable shifts in the 1H NMR signals of β-CD and these can be observed if the titration is carried out in the reverse order. In order to understand the shifts it is essential to assign all 1H NMR signals of β-CD unambiguously. Although this has been reported in the literature,26 we noticed some differences among literature reports.27 Hence we have assigned the 1H NMR signals of β-CD protons using COSY and ROESY experiments (SI, Figure S4). Based on the data obtained the doublet at δ 5.09 ppm is assigned to H-1, the triplet at δ 3.97 ppm is assigned to H-3, the multiplet at δ 3.88 ppm is assigned to H-5 and H-6, the doublet-of-doublet at δ 3.64−3.66 ppm assigned to H-2 and triplet at δ 3.58 ppm assigned to H-4. (Details of this assignment are provided in the SI, Figure S5). Figure 5A shows 1H NMR signals for H-2 to H-6 protons and Figure 5B−D shows the shifts for these signals upon addition of n-BuPMDI (0.36−1.0 equiv.). Considerable upfield shifts (∼0.2 ppm) are observed for the H-3 and H-5 protons. The H-6 protons are shifted upfield to a lesser extent (∼0.04 ppm), but the effects on H-2 and H-4 protons are minimal (≤0.01 ppm). As shown in Figure 1, the H-3, H-5, and one of the H-6 protons are placed in the interior of the CD cavity and the fact that these protons are shifted upfield suggest the presence of some segment of the n-BuPMDI molecule within the β-CD cavity. Since the aromatic proton of PMDI is unaffected (Figure 4), we propose that only the n-butyl group is included within the cavity. Similar results were obtained for other PMDI derivatives (SI, Figures S6 and S7). Results of the 1H NMR experiments thus suggest that the PMDI@β-CD complexes have only the Nalkyl groups of PMDI within the CD cavity and the aromatic moiety is residing outside the cavity. 3.4. Cyclic Voltammetric Studies. PMDI is a redox active chromophore and exhibited two reversible reduction peaks in its cyclic voltammogram. Figure 6 shows the cyclic and square-

Figure 3. Absorption spectra of t-BuPMDI (3.5 × 10−4 M) in the absence and presence of β-CD. [β-CD] varied in the range 0.0 to 3.5 × 10−3 M.

PMDIs are shown in SI, Figure S3). Since the observed changes are very small it was concluded that the PMDI chromophore has very little interaction with β-CD and hence no attempt was made to obtain the binding constants. 3.3. 1H NMR Studies. Figure 4 shows the 1H NMR spectra of t-BuPMDI in the presence of varying amounts of β-CD, where the β-CD concentration changed from 0.36 to 1.0 equiv. As seen from Figure 4, 1H NMR signals of t-BuPMDI exhibited 25006

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Figure 5. 1H NMR titration spectra (zoomed-in image) of β-CD (1.1 × 10−2 M) in the absence (A) and presence (B−D) of n-Bu-PMDI. [nBuPMDI] ranged from 0.36 to 1.0 equiv.

Figure 6. (A) Cyclic voltammogram and (B) square wave voltammogram of t-BuPMDI (red line) without β-CD, (blue line) 5 × 10−3 M of β-CD, and (green line) 10 × 10−3 M of β-CD (potential vs Ag/AgCl).

wave voltammograms of t-BuPMDI in the absence and presence of β-CD. In the presence of β-CD a decrease in the peak currents for both reductions is noticed. E1/2 value for the first reduction remains unchanged whereas the second reduction peak got shifted to more negative E1/2 values. Similar results are observed for other PMDI derivatives (SI, Figure S8). Association of an electroactive guest with a bulky host such as β-CD would results in substantial reduction of the effective diffusion coefficient, leading to a decrease in the current associated with the redox process,28,29 as observed in Figure 6, which confirms the formation of PMDI@β-CD. The PMDIs have a positively charged pyridinium moiety at one end and this part of the molecule is expected to be attracted to the negative electrode and undergo the reduction first. Since E1/2 of this moiety remains unaffected it can be assumed that β-CD does not interact with this imide moiety. The second imide group which is near the alkyl chain appears to be some what shielded due to β-CD interaction resulting in the observed shift of the second reduction peak. The CV studies thus suggest that the βCD−PMDI interaction mostly occur at the alkyl terminus of PMDI. 3.5. Isothermal Titration Calorimetric Studies. In order to gain support for the formation of PMDI@β-CD and to assess the magnitude of the binding constant ITC experiments were carried out. Binding interactions between molecules would involve heat changes and in an ITC experiment these

heat changes can be directly observed and the data can be used to obtain the binding constant (Ka), binding stoichiometry (n), ΔH, ΔG, and ΔS values. ITC experiments were performed by taking β-CD (5 mM, 200 μL) in the cell and excess PMDI (50 mM, 40 μL) in the syringe. Figure 7 shows the ITC titration curve for t-BuPMDI−β-CD system. Heat changes observed for

Figure 7. ITC data of β−CD (5 mM) titrated against t-BuPMDI (50 mM). 25007

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Figure 8. (A) ICD spectra of t-BuPMDI (3.5 × 10−4 M) in the presence of β-CD (0−5 × 10−3 M) and (B) corresponding Benesi−Hildebrand plot.

Figure 9. Possible conformations for t-BuPMDI@β-CD.

exhibited maximum interaction with β-CD. It may be noted that Ka values obtained for t-BuPMDI@β-CD by ITC technique is very close to the value obtained by ICD method. It has been reported that the sign and intensity of the ICD signals depend on the orientation of the guest molecule with respect to the major axis (C7 axis) of cyclodextrin.31−33 The orientation and thereby the geometry of the CD complexes are deduced using a set of rules originally derived for ICD of chiral supramolecular systems which were initially derived for CD complexes and later generalized for complexes of chiral macrocycles.34,35 The rules predict that (1) The sign of ICD is positive for a transition polarized parallel to the axis of the macrocyclic host and negative for that polarized perpendicular to the axis. (2) The sign of ICD is reversed when a chromophore moves from the inside of the host cavity to the outside, while keeping the direction of the transition moment unchanged. (3) The absolute value of ICD is greater when a chromophore exists on the outside of the narrower rim than when it is on the outside of the wider rim. (4) The ICD value of a transition polarized perpendicular to the axis of a macrocycle is −1/2 of that of a parallel-polarized one and the sign of ICD changes at 54.7°.36−39 The lowest energy absorption of PMDI molecule is at 321 nm and is polarized along the axis connecting the two imide nitrogen atoms.40 Hence if the molecule is oriented parallel to the major axis of β-CD and included into the cavity we expect a positive ICD and if it is outside the cavity in the same orientation sign of ICD would be negative. All PMDI molecules under study exhibited negative ICDs in the presence of β-CD. The results suggested that the PMDI chromophore is placed outside the β-CD cavity in these complexes. A negative ICD signal can also arise if PMDI is included in a perpendicular manner inside the cavity. This is ruled out because the length of the t-BuPMDI (∼0.98 nm) is much larger than the inner diameter of β-CD cavity.

t-BuPMDI−β-CD complexation is high and fit of the data yielded values of Ka = 3360 ± 133 M−1, ΔH = (−3.643 ± 0.02621) × 104 J mol−1, ΔS = −52.6 J mol−1 deg−1, and n = 0.81 ± 0.004. The dilution experiment of t-BuPMDI yielded very small heat changes. For other PMDI derivatives heat changes observed were small and data could not be fitted and hence binding constants could not be determined by the available protocols (SI Figure S9). For t-BuPMDI@β-CD the ITC data indicated 1:1 stoichiometry of the components. For the n-BuPMDI@β-CD and 2-PrPMDI@β-CD the stoichiometry could not be established from ITC data. In order to establish the stoichiometry in these cases we have carried out NMR titration experiments. Job’s plot for 2-PrPMDI@β-CD is presented in the SI section (Figure S10). Similar data was obtained for nBuPMDI@β-CD. These results unequivocally established the 1:1 stoichiometry of PMDI@β-CD complexes studied herein. 3.6. Induced Circular Dichroism Studies. Molecules that are not optically active generally show ICD spectra when associated with cyclodextrins due to chirality transfer. This induced optical activity arises due to perturbation in the electronic transition of the guest molecule, by the chiral field of the inducer.30 Due to high overall symmetric structure of the cyclodextrin cavity intensities of the ICD signals from CD complexes are generally low. PMDI derivatives do not exhibit circular dichroism but when associated with β-CD they exhibit ICD. Signs of ICD signals were negative and maximum intensity obtained in the presence of β-CD (5 × 10−3 M) were −4.1, −6.3, and −12.7 mdeg for 2-PrPMDI, n-BuPMDI, and tBuPMDI, respectively. As an example the ICD spectra of tBuPMDI (3.5 × 10−4 M) in the absence and presence of β-CD (1.5 × 10−4 M to 5 × 10−3 M) are shown in Figure 8. We have used the ICD data to obtain Ka values using Benesi− Hildebrand plots assuming 1:1 stoichiometry, and the values obtained were 300 (2-Pr), 700 (n-Bu), and 3315 M−1 (t-Bu), indicating that among the three systems studied t-BuPMDI 25008

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Figure 10. ICD spectra of t-BuPMDI (3.5 × 10−4 M) - β −CD (1.5 × 10−3 M) complex in the absence (blue line) and presence (red line) of (A) adamantane-1-carboxylate (1.5 × 10−3 M) and (B) adamantane-1-ammonium chloride (1.5 × 10−3 M).

that β-CD inclusion complex of adamantane-1-carboxylate (ADC, ΔG0 = −25.7 kJM−1) is more stable than that of adamantane-1-ammonium (ADA, ΔG0 = −22.5 kJM−1).46,47 This is explained to be due to the better penetration of ADC into the β-CD cavity (with the carboxylate moiety situated close to the narrow rim), compared to ADA wherein the adamantane group penetrates only partly into the cavity (with the ammonium terminus projecting above the wider rim).46 Thus a considerable percentage of the cavity near the narrow rim is not occupied in the ADA−β-CD complex, where as the cavity is completely occupied in the case of ADC−β-CD complex. Adamantane derivatives form stable inclusion complexes with β-CD and crystal structures of some of these complexes are known in the literature.48,49 Since adamantane derivatives exhibit high binding constants with β-CD, they tend to displace almost any type of guests included into the CD cavity.12,50−52 We have attempted displacement experiment of the PMDI moiety from PMDI@β-CD complexes with both ADC and ADA using ICD as probing technique. ICD spectra of the tBuPMDI@β-CD in the absence (blue trace) and presence (red trace) of the adamantane derivatives are shown in Figure 10A,B. The t-BuPMDI−β-CD system exhibits considerable ICD intensity as shown in Figure 10 (3.5 × 10−4 M t-BuPMDI and 1.5 × 10−3 M β-CD). When 1.5 × 10−3 M (equivalent to βCD) ADC was added, the ICD signal disappeared completely, where as addition of an equivalent amount of ADA led only to a reduction in the ICD signal intensity as shown in Figure 10. Results similar to this were obtained for other PMDI derivatives (see SI, Figure S11 and S12). Both ADC and ADA ion enters the β-CD cavity through the wider rim. If the conformation of the PMDI@β-CD complex corresponds to structure D (Figure 9), both adamantane derivatives would have displaced the PMDI leading to disappearance of the ICD signal. If the conformation corresponds to structure E, then ADC would have displaced the PMDI completely leading to disappearance of the ICD signal and ADA would have displaced the PMDI only partially leading to a reduction in the ICD intensity as shown in Figure 10B. The displacement experiment showed that PMDI interacts with β-CD through the narrow rim as shown in Figure 9E. In this conformation most of the PMDI chromophore is outside the cavity and binding to the CD is through the narrow rim and hence we designate these as “rim-binding” complexes. In this conformation the imide carbonyl groups on the alkyl side are situated very close to the 6-OH groups of β-CD and most probably these would be involved in hydrogen bonding interactions lending additional stability for the complex. The rim-binding association proposed here is distinctly different

Based on geometrical considerations, the five conformations shown in Figure 9 are possible for PMDI@β-CD. We did not consider conformations where the PMDI is placed horizontally with in the cavity due to geometrical restrictions. We also did not consider any conformations where the charged pyridinium end group is placed within the cavity. Based on ICD results conformations A, B, and C are ruled out because these conformations are expected to generate positive ICD signals. Additionally, in a previous report we have shown that 2PrPMDI forms true inclusion complex with β-CD substituted at the narrow rim with an anthracene moiety (designated as ANCD).22 Positive ICD signals with high intensity could be obtained for the ANCD−2-PrPMDI inclusion complex. The ANCD−2-PrPMDI complex also exhibited considerable shift and broadening of NMR signals for the 2-propyl protons and PMDI aromatic protons.20 For the 2-PrPMDI@β-CD complex reported here changes observed in the 1H NMR signals were insignificant compared to the ANCD−2-PrPMDI inclusion complex. Conformations D and E stand as possible candidates for tBuPMDI@β-CD complex. In conformation D the PMDI is positioned at the wider rim of β-CD with the t-Bu group inserted into the cavity, whereas in E the PMDI is positioned at the narrow rim. The end-to-end distance of the methyl protons of the t-Bu group is ∼5 Å (Figure 1). The inner diameter of the cavity at the wider rim is 7.8 Å and hence the t-Bu group of PMDI is loosely bound at the wider rim in conformation D. Also, the hydrogen bonding interactions between the 2-OH and 3-OH groups at the wider rim is complete in β-CD and hence these hydroxyl groups may not be available for interaction with the PMDI carbonyl groups. In conformation E, the narrow rim offers a tight fit for the t-Bu groups and the free 6-OH groups offers H-bonding interactions with the carbonyls. Thus conformation E appears to be a better choice for the structure of t-BuPMDI @β-CD. In order to make a distinction between the D and E conformations we have carried out two displacement experiments. It is known in the literature that β-CD exhibits a preference for binding anionic guests over cationic guests.15,41 This is due to the electrostatic interaction between the intrinsic dipole moment of the β-CD parallel to the C7 symmetric axis and the charge of the guest.42 In solution β-CD exhibits a dipole moment of 2.9−3.7 D,43 with the partial positive charge situated on the narrow side and partial negative charge on the wider side. As a result, anionic guest molecules such as benzoate anion gets included into the cavity deeply with carboxylate moiety at the narrow rim and cationic guests such as aniline hydrochloride penetrates the cavity only partially with the ammonium end outside the wider rim.44,45 It is also known 25009

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Figure 11. Displacement reactions of t-BuPMDI@β-CD complex with ADC and ADA.

Figure 12. ROESY spectrum of t-BuPMDI@β-CD (1:1) in D2O. For complete spectrum see SI Figure S15.

from “partial inclusion complexes”. Partial inclusion occurs when a guest molecule is sterically prevented from penetrating deep into the CD cavity. In the case of PMDI there are no steric factors that prevent inclusion into β-CD cavity. In fact PMDI forms inclusion complexes when the narrow rim is capped with anthracene.20,22 Moreover, literature reports available for partial inclusion deals with partial inclusion through the wider rim. To the best of our knowledge there are no reports in literature where a molecule forms partial inclusion involving the narrow rim of β-CD, when the molecule could have been actually included inside the cavity through the wider rim. The term “rim-binding” is used here to describe complexation where a molecule prefers partial inclusion through the narrow rim over partial or full inclusion complexation. It may be noted that attempted displacement of PMDI from PMDI@β-CD by ADA results in the formation of a “ternary complex” consisting of PMDI, β-CD and ADA (Figure 11). It is to be mentioned that ternary complexes of cyclodextrins are known in the literature. For example, if two small hydrophobic

molecules are dissolved in water in the presence of CD, these molecules can coexist inside the cavity if such inclusion is sterically possible. Co-inclusion of pyrene with small donors such as triethylamine into a CD cavity is reported previously.53−55 The ternary complexes reported in this paper are different from the coinclusion type ternary complexes and is designated as PMDI⊃β-CD⊂ADA. Thus an important outcome of this study is the realization that it is possible to design ternary complexes wherein the β-CD simultaneously accommodates two guests through different binding modes. In a recent communication we reported utilization of ternary complex formation to design supramolecular hydrogels.21 3.7. NMR Analysis. In order to further confirm the assignment of conformation E (Figure 10) as the structure of PMDI@β-CD, NOE experiments were carried out to obtain information about intra- and intermolecular distances of protons in the complex. Application of traditional NOESY methods is limited by the unfavorable tumbling rates of the molecules in the mass range of 1000 to 2000 Da.26 Hence, to probe the through space interactions in CD complexes spin25010

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Figure 13. Zoomed in image of ROESY spectrum of (A) 2-PrPMDI (2.0 × 10−2 M) with β-CD (2.0 × 10−2 M) and (B) zoomed in image showing the interaction of the methine multiplet with CD inner protons. For complete spectrum see SI Figure S16.

Upon zooming in we could, however, see a cross peak of the methine proton with the β-CD multiplet at δ 4.34 ppm (Figure 13 B). Since both H-3 and H-6 protons contribute to this peak it is very difficult to assign the proton responsible for the cross peak. The methine multiplet is expected to interact with the H3 proton in the inclusion mode and the H-6 proton in the rimbinding mode. In a previous paper we have shown that inclusion binding of 2-PrPMDI in ANCD results in coalescence of the doublet due to the methyl protons into a broad singlet. Since the doublet structure is retained for the methyl protons in the present case we rule out inclusion binding and propose that the cross peak results from interaction of the methine proton with the H-6 proton of β-CD, which confirms conformation E (Figure 9) for the complex. It may be noted that the cross peak is centered more on the H-6 proton than on H-3 proton in Figure 13 B. Figure 14 shows the ROESY spectrum of n-BuPMDI@β-CD. Protons of the n-butyl group are marked Ha, Hb, Hc, and Hd and 1H NMR signals of these occur at δ 0.93 (triplet, 3 H), 1.34 (m, 2 H), 1.66 (m, 2 H), and 3.73 (t, 2 H), respectively. The Ha, Hb, and Hc protons exhibit only very minor changes in their chemical shift or splitting pattern upon complexation with βCD. In an earlier report we have shown that inclusion binding of n-BuPMDI with ANCD results in considerable upfield shifts for all (except for the pyridinium) protons. The alkyl protons experienced considerable broadening, loss of splitting pattern and shifts in the 0.3−0.7 ppm range. The PMDI aromatic protons also shifted by 0.4 ppm with considerable broadening. Absence of signal broadening and retaining of splitting pattern are confirmatory evidence for rim binding in the present case. Figure 14 shows that the Ha, Hb, and Hc protons exhibited cross peaks with the H-3, H-5, and H-6 protons of β-CD. The distance between the 3-H and 6-H protons in the β-CD cavity is >5 Å. If we assume rim binding interaction with the n-butyl chain assuming a straight conformation, it would be difficult to conceive through space interactions of any of the alkyl protons with both H-3 and H-6 protons. This suggests that the butyl chain probably assumes a bent conformation within the CD cavity. Displacement experiments described in section 3.4 showed that β-CD can simultaneously bind to PMDI and ADA leading

lock technique such as rotating-frame overhauser effect spectroscopy (ROESY) is reported to be ideal.56 We have carried out ROESY experiments for all the PMDI@β-CD complexes. In all cases COSY experiments were also carried out to unambiguously identify the intermolecular component and preclude the intramolecular interactions. (SI Figures S13 and S14 for representative examples) If protons of the guest molecule come within ∼4 Å of the β-CD hydrogens through space interactions would occur and these will be observed as cross peaks in ROESY. Thus ROESY can be used to specify the location of guest molecules in CD cavities and several such reports are available in the literature.57−65 ROESY of t-BuPMDI@β-CD (1:1) complex is shown in Figure 12. An important observation is that the PMDI aromatic proton (δ 8.23 ppm) did not exhibit cross peaks with any of the inner protons of β-CD, confirming that the aromatic moiety of PMDI is not included into the β-CD cavity. The t-butyl protons of PMDI (marked as Ha in Figure 12), which appeared as a singlet at δ 1.75 ppm, however, showed cross peaks with the H3 and H-5 protons of β-CD. The PMDI−β-CD interaction has led to 0.04 ppm upfield shifts for H-3 and H-5 protons. The H5 and H-6 protons in native β-CD appeared together as a multiplet, (SI Figures S4 and S5) but in t-BuPMDI@β-CD the H-5 protons are shifted upfield and the H-6 protons are relatively unaffected resulting in spatial separation of these peaks as shown in Figure 12. It is clear from the ROESY spectrum that the t-butyl group is placed within the CD cavity in t-BuPMDI-@β-CD, supporting conformation E (Figure 9). A ROESY spectrum of the 2-PrPMDI@β-CD (Figure 13) also supports the above picture. No cross peaks were observed for the PMDI aromatic proton with the β-CD inner protons. The 2-propyl group exhibits a doublet at δ 1.31 ppm (marked as Ha in Figure 13) due to the methyl protons and a multiplet at δ 4.34 ppm (marked as Hb) due to the methine proton. Figure 13 shows cross peaks between Ha and H-3 and H-5 protons of β-CD. The H-3 and H-5 protons also exhibited upfield shifts of 0.05 and 0.04 ppm, respectively, indicating that the methyl protons of the 2-propyl group are placed inside the cavity and lying close to the H-3 and H-5 protons. In the case of the methine proton, intensity of the multiplet is very low and it was rather difficult to see the cross peaks with β-CD protons. 25011

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Figure 14. Zoomed in image of ROESY spectrum of n-BuPMDI (2.0 × 10−2 M) with β-CD (2.0 × 10−2 M). For complete spectrum see SI Figure S17.

Figure 15. ROESY spectrum of ternary complex t-BuPMDI⊃βCD⊂ADA (1:1:1) in D2O (0.5 mL). For complete spectrum see SI, Figure S20.

to the formation of ternary systems. We have carried out ROESY experiments for two ternary complexes also. Analysis of the ROESY spectra of ternary systems requires prior knowledge of the ROESY spectra of the binary ADA−β-CD inclusion complex, which is provided in the SI (Figure S18, protons of ADA are marked with a prime in these figures). In Figure S18 B the Hc′ proton of ADA shows cross peaks only with H-3 of βCD, whereas the Ha′ and Hb′ show cross peaks with H-3 and H5 of β-CD, indicating that ADA is only shallowly included into the cavity with the Hc′ protons projecting above the wider rim. The Hc′ protons would have exhibited cross peaks with H-5 protons if these were included within the cavity. Figure S18 B also shows two cross peaks for the coupling of Ha′ and Hb′ of ADA (intramolecular coupling). ROESY spectrum of the tBuPMDI⊃β-CD⊂ADA ternary system is shown in Figure 15. Since the Ha′ protons of ADA and the t-butyl protons (Ha) of PMDI appear overlapped in the same region, cross peaks between these protons would fall along the diagonal and hence not observable. Note that in the control ROESY experiment (Figure S18 B) two cross peaks were observed between Ha′ and Hb′, but the number of cross peaks increased to three in the ROESY of the ternary system (Figure 15) and the new peak is assigned to the spatial interaction between the Hb′ of ADA and Ha of PMDI. Control experiments in the absence of β-CD did not show this cross peak (SI, Figure S19). Cross peaks between the t-butyl protons of PMDI and Hb′ protons of ADA can arise only if these are arranged close in space as in the ternary structure shown in Figure 11. Since the Ha′−H-3 and Ha′−H-5 interactions appear in the same region as the t-Bu−H-3 and tBu−H-5 interactions, presence of the latter peaks could not be identified in Figure 15.

ROESY of 2-PrPMDI⊃β-CD⊂ADA ternary system (Figure 16) also confirms the structure shown in Figure 11. In the binary complex 2-PrPMDI@β-CD, the 2-propyl protons showed cross peaks with H-3 and H-5 of PMDI (Figure 13). In the ternary complex 2-PrPMDI⊃β-CD⊂ADA, the 2-propyl protons showed cross peak only with H-5 (Figure 16), suggesting that the 2-propyl group is inside β-CD in the ternary complex but has slipped slightly toward the lower rim. All these results support formation of ternary complexes in aqueous solutions containing PMDI, β-CD and ADA in 1:1:1 ratio. In the ternary complex structure shown in Figure 11 the βCD unit actually serves to bring together the adamantyl and PMDI moieties. In other words, β-CD serves as a connector (such as a flange that connects two shafts) that brings the PMDI and ADA units together. We have shown recently that this principle can be extended to design β-CD based hydrogels. Our design consisted of a ditopic molecule with a PMDI residue on one end and an adamantyl moiety on the other end. This ditopic molecule when dissolved in water in the presence of an equivalent amount of β-CD underwent simultaneous inclusion and rim bindings resulting in the formation of long fibers.21 These fibers then entangle enclosing large amounts of water resulting in the formation of hydrogels.21 We are currently engaged in designing other functional systems using ternary complex formation as the basic underlining principle. 25012

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proposed reasonable structures for PMDI@β-CD and PMDI⊃β-CD⊂ADA. We propose that the ternary complex design is capable of generating higher order structures and work in this direction is progressing in our laboratory.

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ASSOCIATED CONTENT

S Supporting Information *

Details on the syntheses, additional MALDI-TOF spectra, electronic absorption spectra, 1H NMR spectra, CV and Square wave votammograms, ITC data, ICD spectra, and 2D ROESY experimental data. 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: gopidaskr@rediffmail.com. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors thank DAE-BRNS and CSIR for financial support. R.K. and A. M. R. are grateful to CSIR for a fellowship. We acknowledge Dr. Vineesh Vijayan and group and Mr. Adarsh B. from IISER−TVM for 2D NMR experiments. This is contribution number NIIST-PPG 335.

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REFERENCES

(1) Szejtli, J. Chem. Rev. 1998, 98, 1743−1753. (2) Nepogodiev, S. A.; Stoddart, J. F. Chem. Rev. 1998, 98, 1959− 1976. (3) Raymo, F. M.; Stoddart, J. F. Chem. Rev. 1999, 99, 1643−1663. (4) Wenz, G.; Han, B.-H.; Müller, A. Chem. Rev. 2006, 106, 782−817. (5) Tian, H.; Wang, Q.-C. Chem. Soc. Rev. 2006, 35, 361−374. (6) Harada, A. Acc. Chem. Res. 2001, 34, 456−464. (7) Liu, Y.; Chen, Y. Acc. Chem. Res. 2006, 39, 681−691. (8) Comprehensive Supramolecular Chemistry; Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Vögtle, F., Szejtli, J., Osa, T., Eds.; Pergamon: Oxford, U.K., 1996; Vol. 3. (9) Cyclodextrin Technology; Szejtli, J.; Kluwer: Dordrecht, The Netherlands, 1988. (10) Douhal, A. Chem. Rev. 2004, 104, 1955−1976. (11) Harata, K. Chem. Rev. 1998, 98, 1803−1827. (12) Rekharsky, M. V.; Inoue, Y. Chem. Rev. 1998, 98, 1875−1917. (13) Connors, K. A. Chem. Rev. 1997, 97, 1325−1358. (14) Hedges, A. R. Chem. Rev. 1998, 98, 2035−2044. (15) Wenz, G.; Strassnig, C; Thiele, C.; Engelke, A.; Morgenstern, B.; Hegetschweiler, K. Chem.Eur. J. 2008, 14, 7202−7211. (16) Hallén, D.; Schön, A.; Shehatta, I.; Wadsö, I. J. Chem. Soc., Faraday Trans. 1992, 88, 2859−2863. (17) Rekharsky, M. V.; Mayhew, M. P.; Goldberg, R. N.; Ross, P. D.; Yamashoji, Y.; Inoue, Y. J. Phys. Chem. 1997, 101, 87−100. (18) Ross, P. D.; Rekharsky, M. V. Biophys. J. 1996, 71, 2144−2154. (19) Szejtli, J. Pure Appl. Chem. 2004, 76, 1825−1845. (20) Balan, B.; Sivadas, D. L.; Gopidas, K. R. Org. Lett. 2007, 14, 2709−2712. (21) Krishnan, R.; Gopidas, K. R. J. Phys.Chem. Lett. 2011, 2, 2094− 2098. (22) Balan, B.; Gopidas, K. R. Chem.Eur. J. 2007, 13, 5173−5185. (23) Matsue, T.; Evans, D. H.; Osa, T.; Kobayashi, N. J. Am. Chem. Soc. 1985, 107, 3411−3417. (24) Mohanty, J.; Bhasikuttan, A. C.; Nau, W. M.; Pal, H. J. Phys. Chem. B 2006, 110, 5132−5138. (25) Matsushita, Y.; Suzuki, T.; Ichimura, T.; Hikida, T. J. Phys. Chem. A 2004, 108, 7490−7496. (26) Schneider, H.-J.; Hacket, F.; Rüdiger, V. Chem. Rev. 1998, 98, 1875−1917.

Figure 16. ROESY spectrum of ternary complex 2-PrPMDI⊃βCD⊂ADA (1:1:1) in D2O (0.5 mL). For complete spectrum see SI, Figure S21.

4. CONCLUSIONS In this report we have probed the complex formation between few N-alkyl substituted derivatives of PMDI and β-CD using a variety of techniques. Our studies indicated formation of PMDI@β-CD complexes. Sign of the ICD signals were negative which suggested that the PMDI chromophore is placed outside the β-CD cavity with its long axis parallel to the β-CD axis. We have designated these complexes as “rimbinding” complexes. In the proposed structure of the rimbinding complex, the PMDI molecule is situated near the narrow rim of the β-CD with the alkyl chain inserted into the cavity through the narrow rim. When the alkyl group is t-butyl, it offers tight binding to the narrow end of the cavity resulting in high value for the binding constant. Alkyl groups such as nbutyl and 2-propyl do not fill the cavity leading to loose binding and low binding constants. Addition of ADC led to dissociation of PMDI@β-CD complexes whereas addition of ADA led to formation of ternary complexes PMDI⊃β-CD⊂ADA. ROESY experiments were performed to identify the structures of the binary and ternary complexes. In the rim-binding complexes PMDI@β-CD, the PMDI aromatic proton did not exhibit any cross peaks with any of the β-CD protons, suggesting very that the PMDI moiety is not residing inside the cavity. The N-alkyl protons, on the other hand, exhibited cross peaks with the H-3 and H-5 protons of β-CD indicating that these groups are placed inside the cavity. ROESY experiments on the ternary complexes showed cross peaks between PMDI alkyl protons and ADA protons suggesting that both moieties are coexisting inside the β-CD cavity. Based on these results we have 25013

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(61) Jover, A.; Budal, R. M.; Meijide, F.; Soto, V. H.; Tato, J. V. J. Phys. Chem. B 2004, 108, 18850−18859. (62) Guerrero-Martínez, A.; González-Gaitano., G.; Viñas, M. H.; Tardajos, G. J. Phys. Chem. B 2006, 110, 13819−13828. (63) Guerrero-Martínez, A.; Montoro, T.; Viñas, M. H.; GonzálezGaitano, G.; Tardajos, G. J. Phys. Chem. B 2007, 111, 1368−1376. (64) Zhao, Y.-L.; Benítez, D.; Yoon, I.; Stoddart, J. F. Chem. Asian J. 2009, 4, 446−456. (65) Ishizua, T.; Tsutsumia, H.; Yamamotob, H.; Harano, K. Magn. Reson. Chem. 2009, 47, 283−287.

(27) Angelo, M. L.; Dendai, K. I.; Teixera, M. M.; Santoro, A. M.; Pimenta, M. E.; Corte, S.; Rube, N. D. S. Carbohydr. Res. 2007, 342, 2286−2296. (28) Kaifer, A. E. In Comprehensive Supramolecular Chemistry; Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Vögtle, F., Ripmeester, J. A., Eds.; Pergamon: Oxford, 1996; Vol. 8, pp 499−534. (29) Boulas, P. L.; Gόmez-Kaifer, M.; Echegoyen, L. Angew. Chem., Int. Ed. 1998, 37, 216−247. (30) Zhdanov, Y. A.; Alekseev, Y. E.; Kompantseva, E. V.; Vergeichik, E. N. Russ. Chem. Rev. 1992, 61, 563−575. (31) Harata, K.; Uedaira, H. Bull. Chem. Soc. Jpn. 1975, 48, 375−378. (32) Shimizu, H.; Kaito, A.; Hatano, M. Bull. Chem. Soc. Jpn. 1979, 52, 2678−2684. (33) Shimizu, H.; Kaito, A.; Hatano, M. Bull. Chem. Soc. Jpn. 1981, 54, 513−519. (34) Kodaka, M. J. Phys. Chem. 1991, 95, 2110−2112. (35) Kodaka, M. J. Am. Chem. Soc. 1993, 115, 3702−3705. (36) Park, J. W.; Lee, S. Y.; Song, H. J.; Park, K. K. J. Org. Chem. 2005, 70, 9505−9513. (37) Pagliari, S.; Corradini, R.; Galaverna, G.; Sforza, S.; Dossena, A.; Montalti, M.; Prodi, L.; Zaccheroni, N.; Marchelli, R. Chem.Eur. J. 2004, 10, 2749−2758. (38) Zhang, X.; Nau, W. M. Angew. Chem., Int. Ed. 2000, 39, 544− 547. (39) Kano, K.; Hitoshi, M.; Yoshimura, Y.; Hashimoto, S. J. Am. Chem. Soc. 1988, 110, 204−209. (40) Gawroński, J.; Brzostowska, M.; Kacprzak, K.; Kolbon, H.; Skowronek, P. Chirality 2000, 12, 263−268. (41) Kano, K.; Ishida, Y.; Kitagawa, K. Chem. Asian J. 2007, 2, 1305− 1313. (42) Sakurai, M.; Kitagawa, M.; Inoue, Y.; Chujo, R. Carbohydr. Res. 1990, 198, 181−191. (43) Li, X. S.; Liu, L.; Mu, T. W.; Guo, Q. X. Monatsh. Chem. 2000, 131, 849−855. (44) Huang, M.-J.; Watts, J. D.; Bodor, N. Int. J. Quantum Chem. 1997, 65, 1135−1152. (45) Rontoyianni, A.; Mavridis, I. M.; Hadjoudis, E.; Duisenberg, A. J. M. Carbohydr. Res. 1994, 252, 19−32. (46) Briggner, L. E.; Ni, X.-R.; Tempesti, F.; Wadsç, I. Thermochim. Acta 1986, 109, 139−143. (47) Gelb, R. I.; Schwartz, L. M. J. Inclusion Phenom. Mol. Recognition Chem. 1989, 7, 537−543. (48) Hamilton, J. A.; Sabesan, M. N. Acta Crystallogr., Sect. B 1982, 38, 3063−3069. (49) Czugler, M.; Eckle, E.; Stezowski, J. J. J. Chem. Soc. Chem. Commun. 1981, 1291−1292. (50) McAlpine, S. R.; Garcia-Garibay, M. A. J. Am. Chem. Soc. 1998, 120, 4269−4275. (51) McAlpine, S. R.; Garcia-Garibay, M. A. J. Am. Chem. Soc. 1996, 118, 2750−2751. (52) McAlpine, S. R.; Garcia-Garibay, M. A. J. Org. Chem. 1996, 61, 8307−8309. (53) Kano, K.; Takenoshita, I.; Ogawa, T. Chem. Lett. 1980, 1035− 1038. (54) Kano, K.; Takenoshita, I.; Ogawa, T. J. Phys. Chem. 1982, 86, 1833−1836. (55) Kano, K.; Hashimoto, S.; Imai, A.; Ogawa, T. J. Inclusion Phenom. 1984, 2, 737−746. (56) Inoue, Y.; Kanda, Y.; Yamamoto, Y.; Chû jô, R.; Kobayashi, S. Carbohydr. Res. 1989, 194, C8−C13. (57) Bardelang, D.; Clément, J.-L.; Finet, J.-P.; Karoui, H.; Tordo, P. J. Phys. Chem. B 2004, 108, 8054−8061. (58) Gonzál ez-Gaitano, G.; Guerrero-Martínez, A.; Núñ e zBarriocanal, J. L.; Montoro, T.; Tardajos, G. J. Phys. Chem. B 2002, 106, 6096−6103. (59) Gao, Y.; Zhao, X.; Dong, B.; Zheng, L.; Li, N.; Zhang, S. J. Phys. Chem. B 2006, 110, 8576−8581. (60) Han, Y.; Liu, Y.; Rockenbauer, A.; Zweier, J. L.; Durand, G.; Villamena, F. A. J. Org. Chem. 2009, 74, 5369−5380. 25014

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