Probing polyvalency in artificial systems exhibiting molecular recognition

Journal of Organic Chemistry

Volumn 67, Issue 23, 2002, Pages 7968-7981

  Fulton, David A ^a   Cantrill, Stuart J ^a,b   Stoddart, J Fraser ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b California Institute of Technology   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

POLYVALENCIES;

ETHERS; FLUORINE; MOLECULAR STRUCTURE; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY;

COMPLEXATION;

GLYCOCONJUGATE; BENZYLAMINE DERIVATIVE; CYCLODEXTRIN; DIBENZYLAMINE; ETHER DERIVATIVE; FLUORINE; LIGAND;

ARTICLE; COMPLEX FORMATION; MOLECULAR INTERACTION; MOLECULAR RECOGNITION; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; REACTION ANALYSIS; SYNTHESIS; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; TITRIMETRY;

BENZYLAMINES; BINDING SITES; CYCLODEXTRINS; ETHERS, CYCLIC; FLUORINE; LIGANDS; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; TITRIMETRY;

EID: 0037111599     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo0110799     Document Type: Article

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54. +.
55. We have chosen to use binding isotherms, rather than Scatchard plots, to display our data. The main advantage of displaying data in Scatchard plots is that curvature of the data points suggests positive or negative cooperativity. (For a recent example of the use of Scatchard plots in determining the degree of cooperativity in a host-guest system similar to ours, see: Gibson, H. W.; Yamaguchi, N.; Hamilton, L.; Jones, J. W. J. Am. Chem. Soc. 2002, 124, 4653-4665.) Nonideal polyvalent systems are invariably uncooperative. It should be noted that Scatchard plots are mathematical approximations of the actual binding isotherm and thus are subject to the limitations of such an approximation. (There is some controversy about the advantages and limitations of Scatchard analysis; see ref 24b, as well as Klotz, I. M. Acc. Chem. Res. 1974, 7, 162-168). We decided, therefore, to model our systems on a 1:1 binding isotherm - arguably the purest way in which to represent receptor - ligand interactions - as polyvalent interactions can be simplified in their analysis to the interaction between one ligand and one receptor. Our experimental evidence reported in this paper suggests that this model is a valid one.
56. We have chosen to use binding isotherms, rather than Scatchard plots, to display our data. The main advantage of displaying data in Scatchard plots is that curvature of the data points suggests positive or negative cooperativity. (For a recent example of the use of Scatchard plots in determining the degree of cooperativity in a host-guest system similar to ours, see: Gibson, H. W.; Yamaguchi, N.; Hamilton, L.; Jones, J. W. J. Am. Chem. Soc. 2002, 124, 4653-4665.) Nonideal polyvalent systems are invariably uncooperative. It should be noted that Scatchard plots are mathematical approximations of the actual binding isotherm and thus are subject to the limitations of such an approximation. (There is some controversy about the advantages and limitations of Scatchard analysis; see ref 24b, as well as Klotz, I. M. Acc. Chem. Res. 1974, 7, 162-168). We decided, therefore, to model our systems on a 1:1 binding isotherm - arguably the purest way in which to represent receptor - ligand interactions - as polyvalent interactions can be simplified in their analysis to the interaction between one ligand and one receptor. Our experimental evidence reported in this paper suggests that this model is a valid one.
57. To aid clarity, all binding isotherms presented in this work have been plotted using the approximation that [free ligand] = [total ligand].
58. AVE.
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61. Although this signal is broad, we believe that it is still possible to obtain an accurate value for its area by integration.
62. AVE in this system obviously is very low.
63. It appears from the data presented in Table 1 that the magnitude of this detrimental binding effect, which occurs when crown ethers are clustered, is somewhat more pronounced in the DB24C8 systems than in the BMP25C8 systems. There are two principal reasons, however, why it is unwise to draw comparisons between the DB24C8 and BMP25C8 systems. First, these systems were studied at different concentrations of crown ether moieties; in the DB24C8 system, the concentration of crown ethers was kept constant at 7 mM, while in the BMP25C8 system, the concentration of crown ethers was kept constant at 14 mM. Recent research (Chang, T.; Heiss, A. M.; Cantrill, S. J.; Fyfe, M. C. T.; Pease, A. R.; Rowan, S. J.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. Org. Lett. 2000, 2, 2947-2950) has indicated that the binding of dibenzylammonium cations by crown ethers is concentration dependent, that is, association constants can differ depending on the concentrations at which they are measured. Second, the DB24C8 and BMP25C8 systems are, almost certainly, not identical in terms of the enthalpy and entropy changes that occur when dibenzylammonium cations are bound. Again, it is concluded that it is unwise to draw comparisons between them.
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65. 2 would be expected statistically to be 2, rather than 4.
66. AVE.
67. The possibility exists that dibenzylammonium cations can be bound by two crown ether moieties - contained within a single cluster - in a sandwich-like complex, as opposed to in a threaded pseudorotaxane-like geometry.
68. 2 = ca. 2.2) once again seem to suggest that positive cooperativity is in effect.
69. 1H NMR spectroscopic techniques.
70. It should be noted, however, that great care must be taken when making generalizations on the importance of statistical contributions to polyvalency based on the results reported here. The component interaction used in this study involves positively charged ligands and neutral receptors, which leads to complexes with resulting overall positive charge, a factor that is detrimental to the ability of the complex to further bind ligands. This phenomenon would not occur with a polyvalent system in which both the receptor and ligand, and their resulting complexes, have no overall charge.
71. We do not wish to imply that it is easy to achieve significant enhancements in binding in multivalent systems over monomeric ones merely by force of numbers alone. These systems must still be designed such that recognition sites are ligated optimally, which means that, among other considerations, spacer units, linkers, and hubs must be complementary, relatively conformationally rigid, and not too sterically bulky so as to disturb the molecular recognition event.