J. Phys. Chem. 1993,97, 4887-4890
4887
ARTICLES Dynamic Interaction of TCNQ- with fi-Cyclodextrin: A Two-Dimensional NMR Exchange Study Cynthia J. Hartzell,' Scot R. Mente, Nathan L. Eastman, and Jackie L. Beckett Department of Chemistry, Northern Arizona University, Flagstaff; Arizona 8601 1-5698 Received: August 12, 1992; In Final Form: February 22, 1993
Complexation of reduced tetracyanoquinodimethane (TCNQ-) with j3-cyclodextrin results in the formation of a a-bonded dimer, (flCD-TCNQ)22- (J. L. Beckett et al., 1992). lH and I3CNMRshow peaks for 8-cyclodextrin both free and in (j3CD-TCNQ)22-. By use of 2D lH exchange spectroscopy, it is shown that j3-cyclodextrin is undergoing slow exchange at rates from 0.9 s-1 at 30 OC to 5.6 s-l at 42 OC. The temperature dependence of the rate constant yields an activation energy of 128 kJ/mol.
Introduction We report a 2D NMR exchange study of j3-cyclodextrin with T C N Q . The cyclodextrinsare water-soluble cycloamylosesthat contain a hydrophobic cavity with an inner width of 4.5,7, and 8.5 A for cy-, j3-, and ycyclodextrin. Inclusion complexes formed between cyclodextrins and a variety of organic molecules' have been studied extensively as models for molecular receptors.2 Cyclodextrins are also used for chromatographic separations and microencapsulation of drugs.3~~Recently, investigators have reported the formation of insulated polymers by the threading of cyclodextrins along a polymer chain.5 NMR studies have yielded information on the structure of cyclodextrininclusion c o m p l e x e ~ .Previous ~ ~ ~ studiesof the effects of included molecules on the NMR spectrum of j3-cyclodextrin have shown a change in the chemical shift of j3-cyclodextrin resonances as a function of the ratio of included species to j3-cyclode~trin.~~~ This continuous change of shift reflects an averaging of free and included j3-cyclodextrin signal resulting from the fast equilibrium of formation and di~sociation.~Although EPR studies of spin probes in cyclodextrin solutions have shown two signals, corresponding to included and free species? such a distinction has not been reported for NMR studies. We have recently reportedlo that complexationof j3-cyclodextrin with the radical anion of tetracyanoquinodimethane(TCNQ-) results in the formation of a diamagneticproductthat is a cr-bonded dimer, (@CD-TCNQ)22-. This product results from dimerization of the TCNQ radical anion-j3-cyclodextrin complex j3CD-TCNQ. Solutions of TCNQ- in the presence of excess j3-cyclodextrin are unique in displaying discrete NMR signals for (j3CD-TCNQ)zZand free j3-cyclodextrin. Such behavior is consistent with slow exchange of j3-cyclodextrin between the product and the free state. Two-dimensional exchange spectroscopy]' is valuable for the elucidation of slow exchange12 processes. It is a particularly valuable technique for situations in which the one-dimensional coalescence spectra cannot be obtained. This work reports the use of 'H2D exchange spectroscopy (EXSY)to study slow exchange of j3-cyclodextrin with (j3CD-TCNQ)z2-.
Experimental Section The j3-cyclodextrin and 6-tosyl-@-cyclodextrin(Advanced Separation Technologies Inc., Whippany, NJ) were used as received. TCNQ (Aldrich Chemical Co., Milwaukee, WI) served as the starting material for the synthesis of the alkali metal salts of TCNQ-.I3 0022-3654/93/2097-4887%04.00/0
NMR spectra were obtained on a Varian GEMINI-200 spectrometer at frequencies of 200.0 MHz for IH and 50.3 MHz for I3C. The 90° pulses were 22.5 p s for IH and 21 p s for I3C. Relaxation delays of 1 s were used. One-dimensional I3Cspectra were obtained with nuclear Overhauser enhancement. Proton and carbon assignments were obtained from 2D heteronuclear correlationspectra1"I6 and homonuclear J-resolved2D ~ p e c t r a ' ~ J ~ as reported previously.1° Longitudinal relaxation times were determined by using an inversion-recovery pulse sequence, T-T*/2-acquire. The GEMINI is equipped with a variabletemperature controller and probe. The 1D studies were carried out at temperatures ranging from 11 to 50 "C. Sample temperature calibration was carried out by using an external methanol sample. Temperatures were determined as a function of peak separation. The 1H EXSY experimentswere carried out by using the phasesensitiveNOESY pulse sequence, (*/2),-t I -( T / /. 2)xtz(acquire). During the experiment, 256 FID's (128 for each phase) of 512 points each were collected. Each FID consisted of 32 transients. The sweep width in bothfi andfi was 1000 Hz. The r / 2 pulse width was 22.5 s. The T,,, values studied were 0.05, 0.1,0.2,0.3, and 0.5 s. The peak intensities were determined by volume integration. The cross-peak volumes are given as the average of the symmetry-related peaks. The solution studied was 12.5 mM TCNQ-/25.0 mM 8-cyclodextrin in D20. The 2D experiments were carried out at temperatures from 11 to 50 OC.
1D NMR Studies Both 'Hand I3Cspectra of a solution that is 12.5 mM TCNQand 25.0 mM 8-cyclodextrinin D20 at 34 "C are shown in Figure 1. The assignments, as determined previously,IO are given in Table I. The labeling of the glucose ring in j3-cyclodextrin is shown in Figure 1. The most notable feature of both spectra is theclear delineation of the H(1) and C( 1) peaks of j3-cyclodextrin and (j3CD-TCNQ)22-, labeled C and T, respectively,in the figure. To investigatethe possibility of slow exchange of @-cyclodextrin between the free state and (BCD-TCNQ)22-, ID 'Hand I3C variable-temperature studies were carried out between 11 and 50 OC on a solution that was 12.5 mM TCNQ- and 25.0 mM @-cyclodextrin. The chemical shift values for H(1) and C( 1) at each temperature are collected in Tables I1 and 111, respectively. In both the 'Hand 13C spectra, the peaks due to 8-cyclodextrin and (j3CD-TCNQ)22- move downfield as the temperature is increased. However, the only move toward coalescence of the peaks occurs at 50 OC. For proton H(l), the peak difference drops from 0.08 1 ppm at 42 OC to 0.069 ppm at 50 OC. At this 0 1993 American Chemical Society
Hartzell et al.
4888 The Journal of Physical Chemistry, Vol. 97, No. 19, 199'3 4.80 4.90
4 4 PPm
56
3oo
30
B TC
4.g61340 85
110
60
PPm
Figure 1. 1D IH-and i3C-NMRspectraofa1:2mixtureofTCNQ-and j3-cyclodextrin. Peaks for position 1 of j3-cyclodextrin (C) and (j3CD-TCNQ)2*- (T/CD) are indicated. Numbering of the glucose ring of j3-cyclodextrin is shown.
TABLE I: 'Hand 'JC NMR Chemical Shift Values for 8-Cyclodextrin (CD) and (BCD-TCNQ)22-(T/CD) in D20 at 28
oca
C
sample
' 3c
1
CD T/CD CD T/CD CD T/CD CD T/CD CD T/CD CD T/CD
104.7 106.0 74.9 75.3 75.9 75.9 83.9 83.9 74.6 74.8 63.1 62.6
2 3 4 5 6
'H
3.59 3.74 3.58
11
4.8 1 4.88 5.06 5.13 5.17 5.15
20 30 34 38 42
TABLE 111: Temperature Variation of Values for C( 1)
T/CD
4.97 5.04 5.09 5.06 1%
Chemical Shift
temp, 'C
T/CD
CD
11
106.1 105.9 106.0 106.1 106.2
104.7 104.7 104.7 104.9 105.0
20 30 40 50
I
5, .. 1 64 j 5.104-j 5 . 1 0 5 . 1 4 5 . 1 0 5 . 0 6 5 . 0 2 4.90 4 . 9 4 F l IPPM)
-
-If-----
5,2 5.24 5 . 2 6 5 . 2 2 5 . 1 8 5.14 5 . 1 0 5 . 0 6 5 . 0 2 F l IPPH)
TABLE XI: Temperature Variation of 'H(1) Chemical Shift for B-Cyclodextrin (CD) and (BCD-TCNQ)z*-(T/CD) CD
5.127
5.03 4.97 3.58 3.51 3.83 3.95
Values are relative to TMS.
temp, OC
4.98 5.005.025.045.06-
temperature, broadening of the proton spectrum is Observed and severe reduction in S / N occurs in the 13C spectrum. This spectral degradation at higher temperatures precludes the use of a onedimensional coalescence study to determine the exchange rate.
2D 1H Studies The IH 2D exchange studies were carried out over the temperature range 11-50 OC. A mixing time of 200 ms proved optimal at the temperatures studied. The T Ivalues for the H(1) signals were determined to be 0.28 s for 6-cyclcdextrin and 0.29 s for (@CD-TCNQ)22-. The optimum mixing timei9is expected to fall between T 1 / 2and 3T1/2,the range 0.14-0.42 s. In these experiments, cross peaks were only observed above 24 OC. The
Figure 2. IH-2D EXSY spectra of a solution that is 12.5 mM TCNQand 25.0 mM j3-cyclcdextrin at 30, 34, and 42 OC. 1D traces through the diagonal and cross peaks are shown to the right.
H( 1) region of the 2D exchange spectra carried out at 30,34, and 42 OC are shown in Figure 2. At 30 OC cross peaks are barely observed, while at the higher temperatures obvious cross peaks appear. Representative traces are shown for horizontal slices through the 2D maps transecting the diagonal and cross peaks. The 2D spectra shown in Figure 2 were acquired at a mixing time of 200 ms. Spectra collected at 35 "C showed dramatic changes as the mixing time was varied. Exchange spectra obtained at mixing times of 50, 100,200, and 500 ms are shown in Figure 3. Cross peaks are not visible at 50 ms but begin to appear at 100 ms and are well formed at 200 ms. The IH 2D EXSY spectra displayed strong cross peaks of the same phase as the diagonal peaks. The cross-peak intensities varied from 20% to 80% of the intensity of the diagonal peaks. This is expected for a system with long correlation time12and is consistent with the relatively large size of 8-cyclodextrin and (OCD-TCNQ)z2-.
Kinetics of Exchange The overall exchangethat is observed is given by the expression BCD'
+ (/3CD-TCNQ)22- ==
+
(/3CD-TCNQ-TCNQ-BCD')2@CD (1) with effective forward and reverse rate constants kl and k-1. The only species visible by NMR are 8-cyclodextrin and (BCDTCNQ)z2-. Although the exchange may well proceed through
Interaction of TCNQ- with j3-Cyclodextrin
1
The Journal of Physical Chemistry, Vol. 97, No. 19, 1993 4889
I
lm= 50ms
i
5.01
i, r l OP"1
,
,
,
,
,
I
,
5:O'
5.1
"
'
'
T I 1W"l
Figure 4. Schematic representation of the a-bonded dimer, (PCDTCNQ)22-.
I
shown, the secondary faces composed of OH(2) and OH(3) are oriented toward each other. The molecule 6-tosyl-j3-cyclodextrin is substituted along the primary face. Optical spectra of a 1:1 solution of TCNQ- and 6-tosyl-/3-cyclodextrin indicate the formation of a diamagnetic product as is observed with &cyclodextrin. Thus, the formation of the diamagnetic product is not hindered by primary substitution at position 6. However, as reported previously,I0 substitution along the secondary face appears to block the formation of the diamagnetic product. These observations suggest a smndary face to secondary faceorientation of the j3-cyclodextriri molecules as shown in Figure 4. In theanalysis ofthe EXSY data, theintensitiesof thediagonal, Zii, and the cross, ZI,, peaks are used to determine a pseudo-firstorder rate constant as described by Macura and Ernst.I2 These peak intensities are related to the matrix, L, and to the mixing time 7,,, by the expression12
1
1
I
Tm=200 ms
Iij = [ e x p ( - ~ ~ ~ ) ] ~ x (5) where is the equilibrium magnetization of species J. The matrix L is formed from exchange constants as well as relaxation terms. In the absence of cross relaxation, this matrix takes the form
k
+ kl
1
5.01
1
511
4 ,
1 /I
IPP*l
-74
50
Figure 3. 'H-2D EXSY spectra of a solution that is 12.5 mM TCNQand 25.0 m M 8-cyclodextrin at 7 , of 50, 100, 200, and 500 ms.
numerous steps, (pCD-TCNQ),'(PCD-TCNQ-) (BCD'-TCNQ-)
4
2(PCD-TCNQ-)
+ BCD' + j3CD + (oCD'-TCNQ-) + (j3CD-TCNQ-) +
(2)
(3)
(BCD-TNCQ-TCNQ-~~CD'),~-(4) the present treatment of the exchange data implies nothing about the intermediate steps of the reaction.Ig The structure of the proposed cr-bonded dimer is shown in Figure 4. Of the three possible orientations of the two j3-cyclodextrin molecules relative to each other, the isomer depicted is supported by studies using 6-tosyl-&cyclodextrin. In the structure
where 1/T, are the longitudinal relaxation rates of the protons at site i. If dipolar cross relaxation were considered significant, the analysis would require a complete relaxation and exchange matrix analysis as described recently by Lee and Krishna.20 The rate constant has been determined2' by assuming a symmetrical two-site exchange with k , = k - l . The exchange studies were carried out on solutions that were equimolar in j3-cyclodextrin and (j3CD-TCNQ)22-, thus @ , equals pT. This treatment yields an expression relating the rate constant to the ratio of the cross-peak intensity and the diagonal peak intensity
I,, 1 + exp(-2krm) -= I , 1 - exp(-2hm)
(7)
In this way, the value of the rate constant, k,is determined from the ratio of the diagonal peak intensity to the cross-peak intensity. The pseudo-first order rate constants for exchange of &cyclodextrin between the free state and the diamagnetic product are given in Table IV for the different temperatures studied. These rate constants are plotted as a function of temperature in Figure 5 . The value of k determined at 34 OC is 2.2 s-I. The rate constant could not be determined at 50 OC due to a merging of the diagonal and cross peaks at this temperature. The variation of rate constants with temperature was used to determine an activation energy of 128 kJ/mol. This value is
Hartzell et al.
4890 The Journal of Physical Chemistry, Vol. 97, No. 19, 1993 TABLE I V Pseudo-First-Order Rate Constant for the Exchange of &Cyclodextrin between the Free State and the Diamagnetic Complex (TCNQ-/&cyclodextrin) as a Function of Temperatures ki 0.9
temp, OC 30 34 38 42
2.2 3.2 5.6
the exchange process at various temperatures. These rate constants indicate a slow exchange process with k's of 0.9-5.6 SKI in the temperature range 30-42 OC. The activation energy for the exchange is consistent with breakage or formation of a weak C-C bond corroborating the conclusion that the diamagnetic product is a u-bonded dimer. The results of the 2D NMR study yield an activation energy in excellent agreement with optical studies. Acknowledgment. Wewish to thank Dr. Michael Eastman for many helpful discussions. Acknowledgment is made to the donors of The Petroleum Research Fund, administered by the ACS, for support of this research. N.E. acknowledges support as an American Chemical Society-Petroleum Research Fund Scholar.
The mixing time is 200 ms.
1.5
References and Notes (1) Bender, M. L.; Komiyama, M. Cyclodextrin Chemistry; Springer: New York, 1978. (2) Komiyama, M.; Bender, M. L. In The Chemistry of Enzyme Action; Page, M. I., Ed.; Elsevier: Amsterdam, 1984. (3) Bergeron, R. J. In Inclusion Compounds; Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Eds.; Academic Press: London, 1984; Vol. 111. (4) Yamamoto, Y.; Inoue, Y. J . Carbohydr. Chem. 1989,8, 29. (5) Harada, A.; Li, J.; Kamachi, M. Nature 1992, 356, 325. (6) Reviews In Inclusion Compounds; Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Eds.; Academic Press: London, 1984; Vol. 1-111. (7) Schneider, H.; Blatter, T.; Simova, S.J. Am. Chem. SOC.1991,113,
*
C
0.5
1996. (8) Inoue, Y.; Okuda, T.; Miyata, Y.; Chujo, R. Carbohydr. Res. 1984, 125, 65. (9) Kotake, Y.; Janzen, E. J . Am. Chem. SOC.1989, 1 1 1 , 5138 and
.
-0.5 0.
I15
.
, 0.00320
.
.
, 0.00325
.
.
I
'
0.00330
I/t(K)
Figure5 Arrhenius plot of the rate constant as a function of temperature for the exchange of 6-cyclodextrin with (BCD-TCNQ)z2-.
quite close to the enthalpy of reaction, -120 kJ/mol, determined by the optical studiesI0 of reaction 4. This value is about onethird the enthalpy of a standard carbonxarbon bond, 348 kJ/ mo1,Z2 and is consistent with the presence of a long C-C bond. Crystal structure^*^-^^ of two ionic crystals of TCNQ- show the formation of a long a-bond between neighboring molecules of TCNQ-. The bond lengths reported in these studies were 1.63 and 1.65 A. Thus, the energy of reaction in the exchange process under study is attributed to the breaking of the u bond in the rate-determining step of the exchange reaction. Conclusion The applicationof 2D EXSY to the dynamicsof 8-cyclodextrin exchange with (BCD-TCNQ)22- has yielded rate constants for
references therein. (10) Beckett, J. L.; Hartzell, C. J.; Eastman, N. L.; Blake, T.; Eastman, M. P. J. Org. Chem. 1992, 57, 4173. ( 1 1) Jeener, J.; Meier, B. H.; Bachmann, P.; Ernst, R. R. J. Chem. Phys. 1979, 71, 4546. (12) Macura, S.;Ernst, R. R. Mol. Phys. 1980,41,95. (13) Melby, L. R.; Harder, R. J.; Hertler, W. R.; Mahler, W.; Benson, R. E.; Mochel, W. E. J. Am. Chem. SOC.1962,84, 3383. (14) Bax, A.; Morris, G. A. J . Magn. Reson. 1981, 42, 501. (15) Bax, A. J. Magn. Reson. 1983, 53, 512. (16) Rutar, V. J . Magn. Reson. 1984, 58, 306. (17) Aue, W. P.; Karhan, J.; Emst, R. R. J . Chem. Phys. 1976,64,4226. (18) Nagayama, K.; Bachmann, P.; Wuthrich, K.; Ernst, R. R. J . Magn. Reson. 1978, 31, 133. (19) Crans, D. C.; Rithner, C. D.; Theisen, L. A. J. Am. Chem. SOC.1990, 112, 2901. (20) Lee, W.; Krishna, N. R. J. Magn. Reson. 1992, 98, 36. (21) Ernst, R. R.; Bodenhausen, G.; Wokaun, A. Principles of Nuclear Magnetic Resonance in One and Two Dimensions; Clarendon Press: Oxford, 1987; Chapter 9. (22) Pauling, L. The Nature of the Chemical Bond; Cornell University Press, 1960. (23) Vu Dong; Endres, H.; Keller, H. J.; Moroni, W.; Nothe, D. Acta Crystallogr. 1977, 833, 2428. (24) Morosin, B.; Plastas, H. J.; Coleman, L. B.; Stewart, J. M. Acta Crystallogr. 1978, B34, 540.
