18112
2006, 110, 18112-18114 Published on Web 08/31/2006
Solvation and Dynamic Behavior of Cyclodextrins in Dimethyl Sulfoxide Solution Toshiyuki Shikata,* Rintaro Takahashi, Takeshi Onji, Yuichi Satokawa, and Akira Harada Department of Macromolecular Science, Osaka UniVersity, Toyonaka, Osaka 560-0043, Japan ReceiVed: July 19, 2006; In Final Form: August 20, 2006
High-frequency dielectric relaxation behavior up to 20 GHz was investigated for plain (R, β, γ) and (62 and 100%) methylated cyclodextrins, CDs, in dimethyl sulfoxide, DMSO, solution. Each hydrogen atom of OH groups of the CDs solvated a DMSO molecule for a residence time of 130-180 ps due to the hydrogen bond formation to an oxygen atom of DMSO, and a few DMSO molecules were included in cavities of the CDs for a while similar to the residence time. The overall rotational relaxation modes of solvated CDs were also observed depending on the effective sizes of the solvated CDs.
Cyclodextrins, CDs, are water soluble cyclic oligosaccharides consisting of 6, 7, or 8 (R, β, or γ) D-glucpyranosyl units, of which remarkable inclusion ability toward many hydrophobic compounds,1,2 including polymers,3 is potentially applicable and has been already widely employed in many practical applications.4,5 Because a lot of applications of CDs have been developed in aqueous systems, the investigation and understanding of the hydration structure and dynamics of CDs in the aqueous media is of course important for new CD applications. On the other hand, dimethyl sulfoxide, DMSO, in which CDs do not form inclusions complexes, is a so-called good solvent for CDs. Understanding of the solvation and dynamics of CDs, including chemically modified CDs, in DMSO solution provides some key information to reveal essential mechanisms of the inclusion complex formation of CDs from a different point of view. We recently found that each hydrogen atom of OH groups of CDs solvated a DMSO molecule for a residence time of 130 ps, and a few DMSO molecules were included in cavities of CDs for a while, similar to the residence time in DMSO solutions via dielectric relaxation, DR, measurements. A DR technique is the most powerful method to detect the existence of electric dipoles in examined systems and to determine relaxation frequencies of the dipoles.6 DR measurements in a high-frequency range up to a few tens of GHz allow us to determine relaxation times and strengths of solutes, CDs, and also of the solvent, DMSO. These experimental data are definitely related to the number and dynamics of solvated DMSO molecules to CDs, when compared to the rotational relaxation time of pure DMSO molecules, which is of τs ) 20 ps (5.0 × 1010 s-1 in an angular frequency, ω) at 25 °C. Besides the DR technique, solvation dynamics analysis via fluorescence emission behavior of probe molecules has been a useful method to detect dynamics of solvent molecules and has been employed also in aqueous and N, N′-dimethylformamide, DMF, solutions of CDs.7,8 Slow solvent relaxation modes on the order of ns have been observed in cavities of CDs in aqueous and DMF solutions using the solvation dynamics technique, and the reason for the presence of the slow solvation modes has been discussed.7,8 Because no (large) fluorescence probe molecules * Corresponding author. E-mail:
[email protected].
10.1021/jp0645667 CCC: $33.50
are necessary in the case of the DR technique, more direct information on dynamics of (dipolar) solvent molecules would be obtained precisely. In this study, high-frequency DR behavior, real and imaginary parts (′ and ′′) of relative complex permittivity vs ω, was investigated for DMSO solutions of CDs, which included plain R-, β-, and γ-CDs, partially (62%) methylated 62mβ-CD and permethylated pmR-, pmβ-, and pmγ-CD with various numbers of hydroxyl, OH, groups per CD molecule, nOH,9 at the concentration ranging from c ) 30 to 110 mM and 25 °C over a wide ω range up to 20 GHz (1.26 × 1011s-1).10 The number of solvated DMSO molecules per CD molecule, m, was precisely determined depending on CD species and nOH. Furthermore, an exchange process of DMSO molecules solvated to CDs and also rotational relaxation times of solvated CDs were determined. To determine exactly the DR contribution of CDs, ∆′ and ∆′′, the total spectra, ′ and ′′, were decomposed into necessary Debye type relaxation components according to the standard dielectric theory.11 Then, c dependent components of real and imaginary parts of complex permittivities for DMSO, ′s(c) and ′′s(c), were subtracted as follows: ∆′ ) ′ - 1 - ′s(c) and ∆′′ ) ′′ - ′′s(c).12,13 Figure 1 shows typical DR spectra: ′, ′′, ′s, ′′s, ∆′, and ∆′′ vs ω, for DMSO solution of γ-CD at c ) 75 mM. The ratio of relaxation strengths of solvent DMSO, s(c)s-1 ) Φ, which represents the fractional dielectric contribution of the solvent DMSO, was evaluated to be 0.786. The dependency of ∆′ and ∆′′ on ω for the sample involved major and minor relaxation modes observed at 1010 and 2 × 108 s-1, as seen in Figure 1, and similar spectra were also observed in solutions of other plain CDs. The relationship between Φ and c contains important information related to the solute volume fraction, φ, and also to the solvation number, m. Φ was well described by eq 1 using the partial molar volumes of CDs, V h CD,14 and DMSO, V h s, and also the relationship φ ) 10-3 V h CDc.12,15
Φ)
1.1 - φ h sc - 10-3mV φ 1.1 + 2
© 2006 American Chemical Society
(1)
Letters
J. Phys. Chem. B, Vol. 110, No. 37, 2006 18113
Figure 1. Angular frequency, ω, dependence of real and imaginary parts of electric permittivity, ′ and ′′, for DMSO solution of γ-CD at c ) 75 mM and 25 °C. The figure also contains the contribution of γ-CD, ∆′ and ∆′′, and of the solvent DMSO, ′s and ′′s. Moreover, solid and broken lines represent ∆′ and ∆′′ for DMSO solution of pmγ-CD at c ) 86 mM and 25 °C.
TABLE 1: Solvation Number, m or mc, Number of OH Groups, nOH, Specific Molar Volume, V h CD, Rotational Relaxation Time, τr, and Effective Radius, r, for Each CD in DMSO Solution CD species
R
β
γ
62mβ
m mc nOH V h CD/cm3mol-1 τr/ns r/nm
19-20
23-24
26-27
9-10
18 587 4.0 1.1
21 702 5.0 1.1
24 974 7.0 1.3
8.0 974 3.2 1.0
pmβ
pmγ
2-3 0 1130 2.6 0.9
3-4 0 1290 3.6 1.0
The values of the determined m, nOH, and V h CD for each CD are summarized in Table 1.The relationship m ) nOH + mc was reasonably recognized in each CD from Table 1; the value of mc for pmR-CD was assumed to be 1-2 because pmR-CD was less soluble in DMSO at temperature higher than 25 °C. Consequently, each hydrogen atom of OH groups in CDs possessed the ability to form a hydrogen bond to an oxygen atom of DMSO, which is strong enough to make the CDs in the solvated state showing high solubility. The fact that pmβand pmγ-CD without OH groups due to the permethylation still kept high solubility suggested the importance of their mc values more than 2 in DMSO, which should be related to another solvation way independent of the hydrogen bond formation via OH groups. A possible solvation mechanism other than the hydrogen bond formation is the trap inclusion of DMSO molecules into cavities of β- and γ-CD. Except for the smallest R-CD, plain and methylated CDs presumably bore a few DMSO molecules included in their cavities, which fully function as solvating DMSO molecules to CDs. A fast relaxation mode found in ∆′ and ∆′′ spectra (Figure 1), which was relatively sharp and reasonably described by one set of Debye type relaxation functions11 with a relaxation time of τex ) 130 ps, irrespective of the species of plain CDs, was assigned to the exchange process of solvated DMSO molecules to CDs.16 After residence time equal to τex, a solvated DMSO molecule is exchanged by another DMSO molecule. Because ∆′ and ∆′′ spectra for pmγ-CD at c ) 86 mM also kept a small relaxation mode at τexc ) 180 ps close to the τex of γ-CDs, as seen in Figure 1, DMSO molecules included in the cavities were also exchanged at the τexc. The concentration normalized relaxation strength of the exchange process, exc-1 (or excc-1), was proportional to the value of m (or mc) with the same proportional constant, as seen in Figure 2. This proportionality is a strong evidence for the assignment of the fast relaxation mode. Although the source
Figure 2. Dependence of the concentration normalized relaxation strength of the exchange process, exc-1 (or excc-1), of solvated DMSO molecules and the overall rotational process, rc-1, of CDs on the solvation number, m (or mc), for all the CD species examined.
SCHEME 1: Schematic Representation of Solvation States of γ- and pmγ-CD in DMSO Solution.
dipoles belonged to DMSO molecules in both the exchange process and the rotational relaxation process of bulk DMSO, the magnitude of relaxation strength per unit concentration of the solvated DMSO molecules in the exchange process, a slope of a line in Figure 2, ex(mc)-1 (and exc(mcc)-1) ≈ 3.6 M-1, h s ) 1.8 M-1. was twice as large as that of bulk DMSO, 10-3s V Such a discrepancy has been noted in some hydrated water molecules in aqueous systems possessing τex sufficiently longer than the rotational relaxation time of bulk water molecules.6(c),12 Consequently, nOH and mc of DMSO molecules are solvated to CDs due to the direct hydrogen bond formation and also the trap inclusion into their cavities with the residence time identical with the τex, as schematically depicted in Scheme 1 for γ- and pmγ-CD. Nandi and Bagchi have proposed a model6(b) similar to our findings, the exchange process of DMSO molecules in and out of cavities of CDs, for the explanation of multimode DR processes widely observed in aqueous biological systems, and their model has been utilized in the discussion of solvation dynamics of water molecules in cavities of partially methylated β-CD and pmβ-CD.8 On the other hand, the slow relaxation mode was well described by one set of Debye type relaxation functions with a relaxation time of τr ) 7.0 ns for γ-CD solutions (Figure 1). The τr values for each CD summarized in Table 1 slightly decreased with decreasing the size of CDs. Moreover, the concentration normalized relaxation strength of the slow relaxation mode, rc-1, which was independent of c, increased with increasing the size of CDs, as seen in Figure 2. These strongly suggest that the slow relaxation mode is assigned to the overall rotational relaxation process of CDs bearing electric dipoles naturally generated in DMSO solution. Because the slow relaxation mode was observed also in solutions of methylated CDs such as pmγ-CD, as found in Figure 1, the replacement of hydrogen atoms of OH groups by methyl groups did not reduce, but increased the magnitude of the total dipoles of CDs. Especially, partial methylation more effectively strengthened magnitudes of CD dipoles than the permethylation, as found in
18114 J. Phys. Chem. B, Vol. 110, No. 37, 2006 62mβ-CD (Figure 2). The Stokes-Einstein-Debye, S-E-D, relationship17 predicts the relationship τr ) 4πηsr3(kBT)-1, where ηs, r, kB, and T are the solvent viscosity, effective solute radius, Boltzmann’s constant, and the absolute temperature, respectively. The effective radii, r, evaluated from the τr values via the S-E-D relationship, slightly shortened by the permethylation, were responsible for sizes of permethylated CDs without hydrogen bonded DMSO molecules, which were smaller than those of plain CDs, as seen in Table 1 and Scheme 1. Acknowledgment. T.O. expresses special thanks to the Center of Excellence (21COE) program “Creation of Integrated EcoChemistry of Osaka University”. Supporting Information Available: Dependence of Φ on c for each CD in DMSO solution. This material is available free of charge via the Internet at http://pubs.acs.org. References and Notes (1) Szejtli, J. ComprehensiVe Supramolecular Chemistry; Szejtli, J., Osa, T., Ed.; Pergamon: Oxford, 1996; Vol. 3, Chapter 5. (2) Szejtli, J. Chem. ReV. 1998, 98, 1743-1753. (3) (a) Harada, A.; Li, J.; Kamachi, M. Nature 1992, 356, 325-327. (b) Harada, A.; Li, J.; Kamachi, M. Nature 1993, 364, 516-518. (c) Harada, A.; Li, J.; Kamachi, M. Nature 1994, 370, 126-128. (4) Bar, R. ComprehensiVe Supramolecular Chemistry; Szejtli, J., Osa, T., Ed.; Pergamon: Oxford, 1996; Vol. 3, Chapter 13. (5) (a) Okumura, Y.; Ito, K. AdV. Mater. 2001, 13, 485-487. (b) Karino, T.; Okumura, Y.; Ito, K.; Shibayama, M. Macromolecules 2004, 37, 6177-6182. (6) (a) Nandi, N.; Bhattacharyya, K.; Bagchi, B. Chem. ReV. 2000, 100, 2013-2045. (b) Nandi, N.; Bagchi, B. J. Phys. Chem. B 1997, 101, 10954-10961. (c) Ono, Y.; Shikata, T. J. Am. Chem. Soc. 2006, 128, 10030-10031. (7) Sen, S.; Suluk, D.; Dutta, P.; Bhattacharyya, K. J. Phys. Chem. A 2001, 105, 10635-10639. (8) Sen, P.; Roy, D.; Mondal, S. K.; Sahu, K.; Ghosh, S.; Bhattacharyya, K. J. Phys. Chem. A 2005, 109, 9716-9722. (9) R-, β-, γ-CD, and 62mβ-CD were purchased from Wacker Chemicals Co. (Adrian). pmR-, pmβ-, and pmγ-CD were synthesized from each plain CD through reaction with sodium hydride and methyl iodide according to Boger, J.; Corcoran, R. J.; Lehn, J.-M. HelV. Chim. Acta 1978, 61, 219-2218. The purity of the obtained permethylated CDs and the degree methylation for 62mβ-CD were confirmed using NMR measurements.
Letters (10) An RF LCR meter (Agilent Technologies, 4287A), equipped with a homemade electrode cell, was operated to determine DR spectra for samples in a frequency range from 1 M to 3 GHz at 25 °C. ′ and ′′ were evaluated as follows; ′ ) CC0-1 and ′′ ) (G - Gdc)C0-1ω-1, where C0, C, G, and Gdc are the capacitance of a (vacant) used electrode cell, that of a sample, conductivity of the sample, and direct current conductivity of the sample due to ionic impurities, respectively. In a frequency range from 50 M to 20 GHz, ′ and ′′ were determined by using a dielectric material probe system (Hewlett-Packard, 85070B), consisting of a network analyzer (Hewlett-Packard, 8720ES). Details were described elsewhere (Imai, S.; Shiokawa, M.; Shikata, T. J. Phys. Chem. B 2001, 105, 4495-4502). (11) According to the standard dielectric theory (For example, Fro¨hlich, H. Theory of Dielectrics; Clarendon Press: Oxford, 1949.), ′ and ′′ are perfectly described by the summation of Debye type relaxation functions of a mode i; i/(1 + ω2τi2) + i∞ (real) and iωτi/(1 + ω2τi2) (imaginary), τi, i, and i∞ represent the relaxation time, strength, and permittivity at the infinitely high ω range for the mode i, respectively. In the case of pure DMSO at 25 °C, some values are determined as follows; τs ) 20 ps, s ) 42.0, and s∞ ) 3.95. (12) Ono, Y.; Shikata, T. J. Phys. Chem. B 2006, 110, 9426-9433. (13) Because small amounts of impure water molecules were substantially contained in samples due to strong hydration of CDs stored in solid state, DR modes clearly assigned to the impure (free) water, with relaxation times of 3-5 ps, were removed from the obtained ′ and ′′. Because the value of solvent rotational relaxation time, τs(c), slightly lengthened with increasing c, the relationships s′(c) ) s(c)/(1 + ω2τs(c)2) + s∞, s′′(c) ) s(c) ωτs(c)/(1 + ω2τs(c)2), and s∞(c) ) Φ(s∞ - 1) were simply assumed. (14) V h CD was evaluated via density measurements of sample solutions at 25.0 °C using a DMA5000 density meter (Anton Paar, Graz, Austria). Because CDs contained small amounts of unremovable water molecules due to strong hydration, the obtained V h CD values possibly include error bounds less than 2%. (15) The permittivity, , of a mixture consisting of a medium (m) and particles (p) can be well described as a function of the particle volume fraction, φ, to be m-1 ) {(1 + p(2m)-1)/(1 - pm-1)-φ}/{(1 + p(2m)-1)/(1 - pm-1) + φ/2}, in a relatively wide φ range (MaxwellGarnett, J. C. Philos. Trans. R. Soc. London, Ser. A 1904, 203, 385-420). In the case of DMSO solution without the solvation effect, m ) s ) 42 and p ∼ 3, the relationship can be approximated to be s(c)s-1 ) Φ ) (1.1 - φ)/(1.1 + φ/2). (16) For more precise expression, two sets of Debye type functions with τex1 ) 101 and τex2 ) 380 ps were necessary irrespective of the species of plain CDs. Because the exchange mode of DMSO molecules included in cavities was found at τexc ) 180 ps in pmβ- and pmγ-CD, the faster τex1 mode is presumably assigned to the exchange mode of DMSO molecules hydrogen bonded to OH groups. (17) Debye, P. Polar Molecules; The Chemical Catalog Co., Inc.: New York, 1929; Chapter 5.
