In the Laboratory
Supramolecular Chemistry: Induced Circular Dichroism to Study Host-Guest Geometry Gonza lez-Alvarez* Francisco Mendicuti and María Jose Departamento de Química Física, Universidad de Alcal a, Alcal a de Henares, Madrid, 28871, Spain *
[email protected] The importance of supramolecular chemistry of host-guest complexes is well-known. Some of the most popular host structures are the donut-shaped cyclic oligosaccharides formed by R-D-glucopyranose units, commonly referred to as cyclodextrins (CyDs). The most well-known are the R-, β-, and γ-CyDs, which are composed of six, seven, or eight pyranose units, respectively. CyDs have been used in many fields because of their numerous applications: drug delivery for medical purposes (1); molecular sensors for selective chemical, pharmaceutical, or environmental analysis (2); to enhance the reaction rate and the enantioselectivity in organic synthesis (3); for practical selective synthesis of target products by covalent, general acid-base, or noncovalent catalysis (4); and so forth. Most of the studies on these host-guest systems have focused on the calculation of the binding or association constants and the stoichiometry of the complexes by using different techniques (5-8). However, the description of the host-guest structure and how the guest is included inside the cyclodextrin have not been extensively examined. NMR can be used to study the structure, but the information obtained is neither direct nor simple and requires a relatively hard and long interpretation of the results. In addition, expensive deuterated solvents are needed to prepare the solutions. The induced circular dichroism (ICD) caused by complexation between the CyCD and the achiral guest is a useful tool to examine the structure of the complex (9-11). The qualitative information provided by this measurement is valuable. The sign and intensity of the ICD signal is structure-dependent and it can be used to identify possible arrangements of the guests and hosts. Figure 1. Schematic explanation of Kodaka's rules.
Background and Overview Circular dichroism (CD) is a spectroscopy technique that detects the differential absorptions of circular polarized light passing through a substance (12). It is common to associate CD with chiral molecules, but these are not the only ones that can exhibit it. A CyD, in spite of being a chiral molecule, does not absorb in the UV-vis region, and as a consequence, it does not exhibit CD. However, when CyD complexes with an achiral chromophore guest that absorbs in this wavelength range but does not show any CD signal by itself, a CD signal can be induced. This phenomenon is known as induced circular dichroism (ICD) (9). CD measurements are usually reported in ellipticity degrees, θ, of the elliptical polarized light that is generated when the circular polarized light interacts with the matter (12). There are many studies where the CD technique is used to study the complexation of guests with CyDs (9-23). Some of the most extensively studied systems are those that use naphthalene derivatives as chromophore guests (11, 13-15). Kodaka
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proposed some simple rules that relate the sign and value of CD signals with the structure of the host-guest complex (16-18). These rules can be summarized as
• If the direction of the chromophore absorption transition moment and the main symmetry axis of the CyD macrocycle are parallel, the ICD signal is positive (Figure 1.1). In contrast, if the absorption transition moment is perpendicular to the main axis, the ICD signal is negative (Figure 1.2). The latter ICD perpendicular-polarized signal value should be -1/2 in magnitude of the former parallel-polarized one. • The magnitude of the ICD signal is greater when a guest is located in the narrow CyD rim than when it is in the wide rim (Figure 1.3). • The ICD signal signs are changed when the chromophore is located partially outside the CyD (Figure 1.4). • When the movement of the guest inside the CyD is hindered because of its size, the ICD signal is more intense than when the guest has some kind of freedom inside the CyD (Figure 1.5).
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Vol. 87 No. 9 September 2010 Journal of Chemical Education 10.1021/ed100276q Published on Web 07/14/2010
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In the Laboratory Table 1. Binding Constants for the 1:1 23DMN-HPCyD Complexes at 25 C Obtained by Fluorescence Spectroscopy Complex
a
K/(L mol-1)a
23DMN-RHPCyD
165
23DMN-βHPCyD
1080
23DMN-γHPCyD
86
Data from ref 19.
The aim of this laboratory experiment is to apply some simple rules for the analysis of a CD spectrum to obtain structural information on a host-guest supramolecular system. The complexation of a naphthalene derivative, dimethyl 2,3-naphthalenedicarboxylate (23DMN), with 2-hydroxypropyl-R-, -β-, and -γ-CyD (HPCyDs) in aqueous medium is described. Experimental Procedure
Figure 2. Absorption spectrum for a 23DMN water solution. The orientations of the absorption transition moments for both 1Bb and 1La absorption bands are shown in the inset.
Chemicals and Apparatus 23DMN (Aldrich, 99%) and R-, β-, and γ-HPCyDs (Aldrich, 0.6 substitution degree) were used as received. Water was used from a Milli-Q system. ICD spectra were obtained by using a JASCO J-715 spectropolarimeter. Sample Preparation The 23DMN chromophore guest has poor water solubility. Thus, a small quantity should be added to ∼25 mL of Milli-Q water and stirred for 24 h, then the saturated solution filtered with a cellulose filter (Millipore, 1 μm diameter). Its absorbance should be checked at the maximum of the intense band centered at ∼245 nm. The absorbance at this band may be too intense, necessitating dilution (10-15 times) to reach a value of 1: high absorbance values can saturate the photomultiplier detection giving the incorrect measurements and low absorption gives low signal-noise ratios. The 23DMN-HPCyD water solutions must be prepared by weight using the 23DMN saturated solution as a solvent. The solution should be stirred for at least 12 h to ensure that the host-guest equilibrium is reached. The quantity of CyD to be used depends on the binding constant of each host-guest system. The ICD signal is related not only to the geometry of the complex, but also to the quantity of complexed form. All the solutions must have the same fraction of complexed guests (0.7 fraction is a reasonable value). Preparing solutions with the same fraction of host:guest for three CyDs makes the ICD only dependent on the threedimensional structure. For a 1:1 stoichiometry of the hostguest complex, the fraction of complexed guest, f2, is related to the initial CyD concentration, [CyD]0, by K ½CyD0 f2 ¼ ð1Þ 1 þ K ½CyD0 where K is the binding constant. The binding constants for the complexes are listed in Table 1. Hazards The CyDs and 23 DMN do not present any hazards as long as they are not swallowed or inhaled. 966
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Figure 3. CD spectra of 23DMN and 23DMN in the presence of R-, β-, and γ-HPCyD water solutions at 25 C.
Results The UV-vis absorption spectrum for 23DMN water solutions or in the presence of HPCyDs exhibits three main bands at ∼245, ∼282, and ∼320 nm, which, according to the Platt's notation (24), are ascribed to the 1Bb, 1La, and 1Lb bands, respectively (Figure 2). Each band corresponds to an electronic transition of the molecule. The 1Bb and 1La transitions are mainly polarized along the long and short naphthalene axis, respectively (Figure 2). The ICD spectra of the most intense 1Bb naphthalene absorption band at 25 C for isolated 23DMN and 23DMNHPCyD water solutions are shown in Figure 3. The ICD spectra for both 23DMN-βHPCyD and 23DMN-γHPCyD systems exhibit a positive band. This band is substantially more intense for the β complex. A weak negative band is shown for the 23DMNRHPCyD solution and the ICD spectrum for the isolated 23DMN guest is not observed (23DMN is an achiral compound). When focusing on the 1La band for 23DMN-βHPCyD, which requires a higher 23DMN concentration (dilute the initial saturated 23DMN solution approximately twice), a faint negative band is obtained.
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In the Laboratory Table 2. βHPCyD Concentrations and θ Values Obtained at the Maximum of the 1Bb Band at 25 C [βHPCyD]/mM 0
θ/mdeg
[βHPCyD]-1/mM-1
θ-1/mdeg-1
0
-
-
0.17
4.14
5.763
0.242
0.23
5.05
4.322
0.198
0.31
7.01
3.241
0.143
0.41
9.13
2.431
0.110
0.82
13.78
1.216
0.073
1.10
16.00
0.909
0.063
1.46
18.90
0.685
0.053
1.95
21.04
0.513
0.048
Figure 4. Structures for the (1:1) 23DMN complexes with R-HPCyD (1 and 2), βHPCyD (3), and γHPCyD (4), obtained from molecular mechanics calculations (19). (Reprinted with permission from ref 19. Copyright 2008 Springer Science and Business Media).
Discussion The positive ICD spectra for β- and γ-HPCyDs suggest that 23DMN guests are axially oriented, that is, long naphthalene axis nearly parallel to the n-fold rotation CD axis (see Figure 1.1). This is corroborated by the change of ICD sign of the 1La band for the 23DMN-βHPCyD system. In addition, the high intensity of the 23DMN-βHPCyD 1Bb band suggests a better fit and deep penetration of 23DMN inside βHPCyD, whose movement is probably quite hindered. The decrease in intensity for the complex with γHPCyD possibly comes from the increase in the cavity size resulting in a slightly worse fit. In contrast, the ICD signal for the 23DMNRHPCyD solution is weak and negative. This can be explained by the fact that 23DMN does not penetrate totally inside the cavity or that the 23DMN is equatorially oriented in the inner RHPCyD cavity. The latter possibility is rather improbable because of the large size of the 23DMN relative to the RHPCyD cavity. The conclusions are in agreement with the reported complex structures obtained from molecular mechanics analysis on the complexation of these three systems (19). These structures are depicted in Figure 4. Expanding the Experiment The qualitative experiment can be expanded by including the calculation of the binding constant and stoichemistry of host-guest complexes by using the ICD technique. The intensity of the ICD measured at the maximum of the band depends on the quantity of complexed form. The 23DMN-βHPCD complexation can be studied from the ICD intensity change of the intensity of the 1Bb band upon βHPCD addition. The
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Figure 5. Ellipticity values, θ, as a function of the [βHPCyD] for the 23DMN-βHPCyD system adjusted to the nonlinear eq 2. The inset shows the linear adjustment fitted to eq 3.
ellipticity values, θ, as a function of the βHPCyD concentration (by keeping the [23DMN] constant in all experiments) are shown in Table 2 and plotted in Figure 5. These data can be fit to a nonlinear equation for a 1:1 complex (6): θ¥ K ½βHPCyD0 ð2Þ θ ¼ 1 þ K ½βHPCyD0 or to the linear equation: 1 1 1 1 ¼ þ θ θ¥ K θ¥ ½βHPCyD0
ð3Þ
where θ¥ is defined as the value of the ellipticity when 100% of the guest is complexed. At 25 C, the analysis gives K = 910 ( 50 L mol-1 for the 1:1 23DMN-βHPCD and a value of θ¥ ≈ 38 mdeg from the intercept. In the literature, there are several examples where Kodaka's rules are applied to clarify the structure of different kinds of CyCD complexes with other naphthalene derivative guests (11, 13-15), as well as, viologens (20), adamantinediazirines (10), benzenes (21-23), pyrenes (25), azulenes (26), and so forth.
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In the Laboratory
Acknowledgment This research was supported by Comunidad de Madrid (CAM S-055/MAT/0227) and Ministerio de Educacion (CTQ200803149; grant to M.J.G.-A.). We acknowledge the assistance of M. L. Heijnen with the preparation of the manuscript. Literature Cited 1. Rosa Dos Santos, J.-F.; Alvarez-Lorenzo, C.; Silva, M.; Balsa, L.; Couceiro, J.; Torres-Labandeira, J.-J.; Concheiro, A. Biomaterials 2009, 30, 1348–1355. 2. Lida, K. Res. J. Chem. Environ. 2008, 12, 102–103. 3. Ghanem, A. Org. Biomol. Chem. 2003, 1, 1282–1291. 4. Koniyama, M.; Monflier, E. Cyclodextrin Catalysis. In Cyclodextrins and Their Complexes; Dodziuk, H., Ed.; Wiley-VCH GmbH & Co. KgaA: Weinheim, 2006; Chapter 4. 5. Smith, V. K.; Ndou, T. T.; Mu~ noz de la Pe~ na, A.; Warner, I. M. J. Inclusion Phenom. 1991, 10, 471–485. 6. Mendicuti, F. Trends Phys. Chem. 2006, 11, 61–77. 7. Valero, M.; Rodríguez, L. J.; Velazquez, M. M. J. Chem. Educ. 1999, 76, 418–419. 8. Gonzalez-Gaitano, G.; Tardajos, G. J. Chem. Educ. 2004, 81, 270–274. 9. Krois, D.; Brinker, U. H. Circular Dichroism of Cyclodextrins Complexes. In Cyclodextrins and Their Complexes; Dodziuk, H., Ed.; Wiley-VCH GmbH & Co. KgaA: Weinheim, 2006; Chapter 10.4. 10. Krois, D.; Brinker, U. H. J. Am. Chem. Soc. 1998, 120, 11627– 11632. 11. McAlpine, S. R.; García-Garibay, M. A. J. Am. Chem. Soc. 1998, 120, 4269–4275.
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12. Circular Dichroism;Principles and Applications, 2nd ed.; Nakanishi, K., Berova, N., Woody, R. W., Eds.; VCH Publishers: New York, 1994. 13. Park, J. W.; Song, H. E.; Lee, S. Y. J. Org. Chem. 2003, 68, 7071–7076. 14. Murphy, S. R.; Barros, T. C.; Mayer, B.; Marconi, G.; Bohne, C. Langmuir 2000, 16, 8780–8788. 15. Yorozu, T.; Hoshino, M.; Imamura, M. J. Phys. Chem. 1982, 86, 4422–4426. 16. Kodaka, M. J. Phys. Chem. 1991, 95, 2110–2112. 17. Kodaka, M. J. Am. Chem. Soc. 1993, 115, 3702–3705. 18. Kodaka, M. J. Phys. Chem. A. 1998, 102, 8101–8103. 19. Usero, R.; Alvariza, C.; Gonzalez-Alvarez, M. J.; Mendicuti, F. J. Fluoresc. 2008, 18, 1103–1114. 20. Park, J. W.; Song, H. E.; Lee, S. Y. J. Phys. Chem. 2002, 106, 7186– 7192. 21. Shimizu, H.; Kaito, A.; Hatano, M. Bull. Chem . Soc. Jpn. 1979, 52, 2678–2684. 22. Shimizu, H.; Kaito, A.; Hatano, M. Bull. Chem. Soc. Jpn. 1981, 54, 513–519. 23. Yang, G. F.; Wang, H. B.; Yang, W. C.; Gao, D.; Zhan, C. G. J. Phys. Chem. B. 2006, 110, 7044–7048. 24. Platt, J. R. J. Chem. Phys. 1949, 17, 484–495. 25. Yorozu, T.; Hoshino, M.; Imamura, M. J. Phys. Chem. 1982, 86, 4426–4429. 26. Abou-Zied, O. K. Spectrochim Acta, Part A 2005, 62A, 245–251.
Supporting Information Available Student handout; notes for the instructor. This material is available via the Internet at http://pubs.acs.org.
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