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β-Cyclodextrin as an End-to-End Connector Retheesh Krishnan and Karical R. Gopidas* Photosciences and Photonics Section, Chemical Sciences and Technology Division, National Institute for Interdisciplinary Science and Technology (NIIST), Council of Scientific and Industrial Research (CSIR), Trivandrum 695 019, India
bS Supporting Information ABSTRACT: Interaction of β-cyclodextrin (β-CD) with a ditopic molecule having adamantane (AD) at one end and a pyromellitic diimide (PMDI) moiety at the other is studied. The AD moiety undergoes inclusion binding with the β-CD cavity, and the PMDI undergoes binding with the primary rim of β-CD. In an equimolar solution of β-CD and the ditopic molecule in water, β-CD accommodates both modes of complexation simultaneously, leading to the formation of long fibers. The fibers get entangled to give a supramolecular hydrogel with very high water content. SECTION: Macromolecules, Soft Matter
β-C
yclodextrin (β-CD) is a toroidal shaped cyclic oligosaccharide with a larger opening lined with secondary hydroxyl groups (secondary rim) and a smaller opening lined with primary hydroxyl groups (primary rim). The β-CD cavity is hydrophobic and can encapsulate small molecules from aqueous solution to give inclusion complexes.1,2 Almost all applications of β-CD are related to complex formation.3 Although inclusion binding is the most common mode of β-CD complexation,4 other modes of binding are also known. We have recently reported a new mode of β-CD binding termed “rim binding” to explain the complexation of β-CD with pyromellitic diimide (PMDI).5 In the rim-binding mode of association, the PMDI remains just outside of the primary rim of β-CD with the N-alkyl group inserted into the CD cavity and the carbonyl groups hydrogen bonded to the primary hydroxyl groups. In this paper we demonstrate that β-CD molecules can accommodate inclusion binding and rim binding simultaneously, and these interactions can repeat themselves as in a polymerization reaction leading to the formation of long fibers that entangle to form a supramolecular hydrogel. The structures of the molecules used in this study (1, 2, and 3) are shown in Scheme 1. The pyridinium moieties in 13 are there for imparting water solubility. Adamantane (AD) derivatives exhibit a very high tendency to form inclusion complexes with β-CD and hence 1 is expected to bind strongly to β-CD with the AD moiety getting encapsulated into the β-CD as shown in Scheme 1. The PMDI derivative 2 is expected to undergo rim binding as shown in Scheme 1 (see ref 5 for details). On the basis of these observations we reasoned that the ditopic molecule 3, having AD moiety on one end and PMDI on the other, would bind two β-CD molecules as shown in Scheme 1, where the AD end is included into the cavity of one β-CD and the PMDI end is rim bound to another β-CD. r 2011 American Chemical Society
Scheme 1. Possible Modes of Interaction of β-CD with 1, 2, and 3
Interactions of 1, 2, and 3 with β-CD were probed by isothermal titration calorimetry (ITC). For each system two sets of ITC experiments were performed (see Supporting Information for details). Figure 1A shows the ITC titration curve for 1 with β-CD (10 mM). A standard titration curve was obtained, which was fitted using a single binding site model, and the binding parameters are given in Table 1. The parameters revealed singlesite binding and high association constant K (≈ 6 104 M1). Received: July 6, 2011 Accepted: August 5, 2011 Published: August 05, 2011 2094
dx.doi.org/10.1021/jz2009117 | J. Phys. Chem. Lett. 2011, 2, 2094–2098
The Journal of Physical Chemistry Letters
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Figure 1. ITC data: (A) 1 and β-CD (10 mM); (B) 2 and β-CD (20 mM); (C) 3 with β-CD (10 mM); (D) 3 with β-CD (20 mM); (E) panel D expanded (see text); and (F) 2 and 1:β-CD complex (1:1, 10 mM).
Table 1. Fit Parameters Obtained from ITC Data Fitting expt.
N sitesa
Kb M1
ΔH kJ mole1
ΔS J mol 1 deg1
A
1
6.09 E4
34.7
22.9
30.0 38.0
16.9 43.9
B C D a
No Fit 1 0.5
1.96 E4 1.97 E4
Number of binding sites. b Binding Constant.
Similar results were obtained even when β-CD concentration was raised to 20 mM. In the case of 2, the ITC experiments showed that heat changes are very small even at 20 mM β-CD (Figure 1B) and the data could not be fitted to any standard model. From Figure 1B we conclude that there is certainly an interaction between 2 and β-CD, but this interaction is slow and the heat liberated during each addition of β-CD is small, and we attribute this to the rim-binding association shown in Scheme 1. In the case of the ditopic molecule 3, the titration curve obtained with 10 mM β-CD is shown in Figure 1C, and the corresponding fit parameters are given in Table 1 (entry C). The data showed high association constant (K ≈ 2 104 M1) and one binding site. The ITC curve for the same system at 20 mM β-CD is shown in Figure 1D, and the fit parameters are given in Table 1 (entry D). Comparing entries C and D, we find that when β-CD is 20 mM, the number of binding sites is reduced to 0.5, and the entropy change ΔS became substantially negative. Reduction of the binding sites to 0.5 at high β-CD concentration suggested
that every molecule of 3 now associates with two β-CD molecules, as shown in Scheme 1. The increased ordering required for the association of three molecules justifies the observed negative entropy change. The ITC titration experiments thus supported the interactions shown in Scheme 1. Although the ITC titration curves in Figure 1C,D appear normal, a close examination reveals that these curves are somewhat complex. If we expand the latter part, i.e., the heat changes observed toward the end of the titration (Figure 1 E), it would look very similar to the heat changes in Figure 1B. On this basis we argue that the interaction of 3 with β-CD proceeds in two steps: a fast step involving the inclusion of the AD moiety, and a slow step that involves the rim-binding of the PMDI moiety with the narrow rim of β-CD. In a control experiment 1 mM solution of 2 was titrated against an aqueous solution of 1:β-CD complex (1:1, 10 mM in each). The titration curve obtained (Figure 1 F) was very similar to that obtained in the case of the 2:β-CD system (Figure 1B), and the data could not be fitted to any model. Since the association constant between 1 and β-CD is very high, we expect the 1:1 mixture to consist mostly of the 1:β-CD inclusion complex. The titration curve obtained suggested that the 1:β-CD complex interacts with 2 in the same way as β-CD interacts with 2. The 1:β-CD complex can interact with 2 only through the rimbinding mode. This experiment supported our argument that the 3:β-CD interaction consists of two steps. We also carried out control experiments to rule out dilution effects. Induced circular dichroism (ICD) experiments were carried out to further confirm the proposed interactions between β-CD 2095
dx.doi.org/10.1021/jz2009117 |J. Phys. Chem. Lett. 2011, 2, 2094–2098
The Journal of Physical Chemistry Letters and 1, 2, and 3. Achiral molecules complexed with β-CD often exhibit ICD spectra, the sign and intensity of which are very sensitive to the orientation of the achiral molecule in the complex, and these can be used to predict the orientation of the guest in the β-CD complex.68 AD has no absorption above 250 nm and hence the 1:β-CD complex did not give an ICD spectrum. Absorption maximum of 2 occurs at 321 nm (Supporting Information (SI), Figure S4A). The 2:β-CD system gave the negative ICD spectrum shown in Figure 2A. 3 did not show a CD spectrum, but an aqueous solution of the 3:β-CD system (1:1) exhibited the negative ICD signal shown in Figure 2B. The ICD results thus suggest that the PMDI moieties of 2 and 3 interact with β-CD through the rim-binding mode of association as shown in Scheme 1 (see ref 5 for details). ITC and ICD results clearly show that the AD part of 3 interacts with β-CD through inclusion binding, and the PMDI moiety interacts with β-CD through rim binding. At this
Figure 2. ICD spectra for (A) 2 (5 104 M):β-CD (5 103 M) and (B) 3:β-CD systems (1 104 M each).
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juncture, one can ask a very interesting question: Will it be possible for the same β-CD molecule to get involved in both modes of binding simultaneously? If this is possible, it would provide a simple mechanism for the formation of supramolecular polymers from β-CD and 3, as shown in Scheme 2. Using molecular models, Breslow et al. previously showed that AD derivatives are included into the β-CD cavity through the secondary side and that the AD moiety occupies only about 65% of the cavity space.9,10 Rim-binding association of 2 with β-CD as shown in Scheme 1 involves insertion of the tert-butyl (t-Bu) group slightly into the narrow rim of β-CD. If the t-Bu group occupies
