J . Am. Chem. SOC.1989, 111 , 2697-2699
2697
Dynamics of Molecular Recognition Involving Cucurbituril William L. Mock* and Neng-Yang Shih Contribution from the Department of Chemistry, University of Illinois at Chicago, Chicago, Illinois 60680. Received September 2, 1988
Abstract: For the synthetic receptor cucurbituril, the rate of inclusion complex formation correlates with the molecular diameter of alkylammonium ion ligands but not with the thermodynamicstability of the complexes formed. Measurements of I3CNMR spin-lattice relaxation allow comparison of molecular tumbling motions of the receptor with those of bound ligands, by determination at their respective correlation times. Guest ions appear to rotate relatively freely within cucurbituril, irrespective of the stability of the complexes. Results are interpreted in terms of shape complementarity between receptor and ligand.
Understanding the phenomenon of biochemical specificity, as observed in enzyme-substrate, antigen-antibody, or hormonereceptor interactions, etc., represents a challenge that is yielding to contemporary investigations. The recent availability of synthetic macrocyclic receptors has greatly aided progress in the area of molecular recognition, by providing models in which systematic study of noncovalent bonding may be pursued. For the most part, these have been thermodynamic investigations,in which the factors contributing to the stability of molecular complexes have been explored. While fruitful, such an approach only partly addresses the question of biochemical specificity. Biological processes are inherently dynamic in nature. For example, it is recognized that enzymes in vivo commonly operate with substrate concentrations below K,,, (Le., with less than “saturating” amounts of reactants in the steady state). Furthermore, conversion of bound substrate may be more rapid than reversal of the binding step. This means that enzymic specificity (in the sense of selection between competing potential substrates) may be a kinetic phenomenon as much as it is a thermodynamic one. Clearly, the dynamics of molecular recognition deserve more attention. Cucurbituril (1) is a synthetic molecular receptor that is readily assembled from urea, glyoxal, and formaldehyde [2H2NCONH2 + CHOCHO C4H6N402(glycoluril), 6C4H6N402+ 12CH20 C24H36N24012 (cu~urbituril)].~It has a hollow interior, which is connected to the exterior by two carbonyl-fringed portals. Studies of the equilibrium binding of aliphatic and aromatic ammonium ions within 1 have previously been r e p ~ r t e d ,as ~ .has ~
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1 catalysis by 1 of a specific cy~loaddition.~Typical ligands of high affinity for 1 are n-alkyl-, and cycloalkylammonium ions of 4-6 carbon atoms. Cross-sectional representations of the n-pentyland cyclopentanemethylammonium ion complexes of 1 are presented in Figure 1. The noncovalent binding interactions may be conceptually divided into two contributions: an ion-dipole attraction leading to coordination of the cationic ammonium ~
~~
(1) Taken in part from the Ph.D. Thesis of N.-Y. Shih, University of Illinois at Chicago, 1981: Dim. Abstr. Int. B 1982, 42, 4071. (2)Freeman, W. A,; Mock, W.; L.; Shih, N.-Y. J . Am. Chem. Soc. 1981, 103, 7367. (3) (a) Mock, W.L.; Shih, N.-Y. J. Org. Chem. 1986, 51, 4440. (b) This technique has previously been used: Anthonsen, T.; Cram, D. J. J . Chem. SOC.,Chem. Commun. 1983, 1414. (4)Mock, W.L.;Shih, N.-Y. J . Am. Chem. SOC.1988, 110, 4706. ( 5 ) Mock, W. L.; h a , T. A,; Wepsiec, J. P.; Manimaran, T. L. J . Org. Chem. 1983, 48, 3619.
0002-7863/89/1511-2697$01.50/0
Table I. Lieand-Receotor Kinetic Data for I ~ O ~ K 1 ~05,k,,,, ligand‘ M s-l
s-I
kin: M-1
Tc, ‘C 2.8 37 (k3) 13.3 2. (CH,),CH(CH2)3NH3+ 24 120 (f3) 5.0 3. 2-C4H3SCHzNH3+c 0.43 9.3 (f0.3) 21.4 4.C - ( C H , S ) ~ C H C H , N H ~ +0.17 ~ 1.6 (fO.l) 9.2 5. c-(CHZ),CHCH,NH,+ 0.30 1.6 (fO.l) 5.5 6.c - ( ( C H Z ) ~ C H C H ~ N H ~ +0.27 1600 (f300) 5900 7. C - ( C H ~ ) ~ C H C H ~ N H , +6.8 >lo7 >lo6 A r / 2 N 124 s-' under the special circumstances described. Relaxation measurements ( T , ) by I3C FT-NMR spectroscopy (20 MHz) were secured c~nventionally.~~' Tolerances listed in this article are for the most part standard errors from least-squares analysis.
Acknowledgment. This work was supported by the Dow Chemical Co. Foundation, the University of Illinois Research Board, and in part by the Office of Naval Research. Registry No. 1, 80262-44-8; (CH,),CH(CH,),NH,+, 62063-10-9; (CH3),CH(CH,)3NH3', 104464-49-5; 2-C,H,SCH,NH,+, 1 19297-72-2; c - ( C H , S ) , C H C H 2 N H 3 + , 1 19297-73-3; c-(CH2),CHCH2NH,+, 119297-74-4; c-(CH,),CHCH,NH,', 119297-75-5; C(CH2)2CHCHlNH,+, 104464-67-7; CH3(CH*),NH3+, 16999-97-6; CH3(CH2)4NH3+,24551-46-0; CH3(CH2),NH3+, 21005-95-8; CH3(CH,),NH,+, 21005-96-9.
