Binding by Cyclodextrin Dimers

BUiang, Z and R Breslow (1993). Enthalpic domination of the chelate effect in cyclodextrin dimers. Journal of the American Chemical Society, 115,9353-9354. Breslow, R and Z BUiang (1996). Cholesterol recognition and binding by cyclodextrin dimers. Journal oftheAmerican Chemical Society, 118(35), 8495-8496. 

R. Breslow, N. Greenspoon, T. Guo and R. Zarzycki, "Very Strong Binding of Appropriate Substrates by Cyclodextrin Dimers" T. Am. 

The stability of the polypyridyl rhenium(I) compounds mentioned above stimulated applications of this coordination chemistry. Thus, new heterotopic bis(calix[4]arene)rhenium(I) bipyridyl receptor molecules have been prepared and shown to bind a variety of anions at the upper rim and alkali metal cations at the lower rim. A cyclodextrin dimer, which was obtained by connecting two permethylated /3-cyclodextrins with a bipy ligand, was used for the preparation of a luminescent rhenium(I) complex. The system is discussed as a model conipound to study the energy transfer between active metal centers and a bound ditopic substrate. The fluorescence behavior of rhenium(I) complexes containing functionalized bipy ligands has been applied for the recognition of glucose. ... 

We also investigated chelate binding by dimers of a synthetic hydrophobic macrocycle, in place ofthecyclodextrins [187]. In the systems examined the chelate effect was weaker than that seen with the cyclodextrin dimers. We also studied the strong binding of cholesterol by some cyclodextrin dimers and a cyclodextrin polymer, and saw that the large sterol could occupy parts of two binding cavities [188]. 

Metalloporphyrins can catalyze the hydroxylations of solvent species such as cyclohexane. From our studies with cyclodextrin dimers, we concluded that by attaching cyclodextrin rings to metalloporphyrins we should be able to bind substrates in water and achieve selective hydroxylations directed by the geometries of the complexes. This was successful. 

Esters can be cleaved by template catalysts that use a metal ion as both a binding group and part of the catalytic system [79-81]. However, metal ion catalysis has also been extended to cases in which the principal substrate binding involves cyclodextrin inclusion indeed, the first catalyst described as an artificial enzyme was. such an example [82]. A cyclodextrin dimer 47 with a bound metal ion between the two cyclodextrins is a particularly effective hydrolytic catalyst for esters that can bind into both cyclodextrin units (Scheme 6-20) [83, 84]. 

Interestingly, in a study of the binding of ditopic substrates to such cyclodextrin dimers we saw that the binding was dominated by an improved enthalpy, rather than entropy. The simplest ideas about chelate binding would have suggested an entropy advantage, but in solution enthalpy-entropy compensation can be seen if the binding or release of water molecules is also considered. 

Helical structures are important in proteins, and the extent of heUx formation in a given polypeptide can be influenced by external factors. In a study related to this question we saw that with appropriate cyclodextrin dimers we could induce helix formation in some oligopeptides if the helix structure presented hydrophobic side chains in a geometry such that our dimer could bind to them, stabilizing the helix. ... 

R. Breslow, B. Zhang, Cleavage of phosphate esters by a cyclodextrin dimer catalyst that binds the substrates together with La and hydrogen peroxide, J. Am. Chem, Soc., 1994,116, 7893-7894. 

R. Breslow, S. Chung, Strong binding of ditopic substrates by a doubly linked occlusive Cl clamshell as distinguished from an aversive C2 loveseat cyclodextrin dimer, J. Am. Chem. Soc., 1990, 112, 9659-9660. 

The 2 2 complex 12 is formed from two cyclodextrin dimers that cross each other and encapsulate two porphyrins. Each porphyrin binds to two cyclodextrins not belonging to the same dimer. The formation of the 2 2 complex is facilitated by the presence of 0.5 equivalent of Zn ions, as shown in 12, which coordinate the bipyridine units in a tetrahedral fashion. 

An interesting feature of the binding of a double-ended substrate into a cyclodextrin dimer is that the substrate is held right on top of the linker group. If that linker carries a catalytic function, one can imagine very effective catalysis of reactions at the middle of the substrate. We have examined a number of such processes, and have achieved some very large catalyses in appropriate cases. Here we will describe catalysis by a cyclodextrin dimer 30 carrying a bipyridyl linker. This linker can bind... 

Halfon, S. (1993) I. Binding and catalysis by beta-cyclodextrin dimers, n. Effects of antihydrophobic agents on binding of beta-cyclodextrin dimers, Ph.D. thesis, Columbia University. 

Inspired by the remarkable efficiency of many enzymes, chemists have tried to prepare artificial systems that operate in form and function like enzymes do. Cyclodextrins are the most extensively used platforms for these efforts. The dominance of cyclodextrins stems from the pioneering observations of Breslow and Tabushi, who showed that simple organic compounds can display many of the hallmarks of enzymatic catalysis, such as binding, rate accelerations, and turnover. However, most artificial systems do not give the large rate enhancements that their natural counterparts impart. One example that does produce a large rate enhancement is based on a cyclodextrin dimer. 

Sequence-selective binding of peptides and small proteins is of considerable interest. We saw that some cyclodextrin dimers could selectively doubly bind peptides in water with appropriately placed hydrophobic side chains. This built on our earlier collaborative work on the selective binding of peptides by simple cydodextrin. We then showed that we could break up a protein dimer and a protein tetramer with appropriate cydodextrin dimers in water, since such protein aggregation ordinarily involved hydrophobic side chains that our dimers could bind to. In perhaps the most striking example, our cydodextrin dimers and trimers were able to inhibit the protein aggregation involved in the formation of Alzheimer s plaques. ... 

Some synthetic macrocycles can bind hydrophobic groups in water similar to the binding into cyclodextrins. We examined the selective binding of some substrates by dimers of such synthetic macrocycles.We have also examined where catalytic groups should be placed on... 

R. Breslow and S. Chimg, "Strong Binding of Ditopic Substrates by a Doubly Linked Occlusive Ci "Clamshell" as Distinguished from an Aversive C2 "Loveseat" Cyclodextrin Dimer", T. Am. Chem. Soc. 112, 9659-9660 (1990). 

Rhodopsin is a seven ot-helix trans-membrane protein and visual pigment of the vertebrate rod photoreceptor cells that mediate dim light vision. In this photoreceptor, retinal is the chromophore bound by opsin protein, covalently linked to Lys296 by a Schiff base linkage. Kpega et al.64 have studied NMR spectra of Schiff bases being derivatives of all-frans retinal and amino-p-cyclodextrins as a model of rhodopsin, where p-cyclodextrin plays a role of a binding pocket. On the basis of analysis of the chemical shift differences for the model compound in the presence and in the absence of adamantane carboxylate, it has been shown that the derivative of 3-amino-p-cyclodextrin forms dimer in water and retinoid is inserted into p-cyclodextrin cavity [31]. 

---