Cyclodextrin dimers

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. ... 

Kikuchi, T. Narita, M. and Hamada, F. (2002) Synthesis of bis dansyl-modified /f-cyclodextrin dimer linked with azobenzene and its fluorescent molecular recognition, J. Incl. Phenom. 44, 329-333. 

Jung, J.H., Takehisa, C., Sakata, Y., and Kaneda, T. (1996) p-(4-Nitrophenylazo)phenol Dye-bridged Permethylated a-Cyclodextrin Dimer Synthesis and Self-aggregation in Dilute Aqueous Solution, Chem. Lett. 147-148. 

We have pursued such ester hydrolysis by artificial enzymes further. With a cyclodextrin dimer related to 25 we have hydrolyzed an ordinary doubly bound ester, not just the more reactive nitrophenyl esters [116], with catalytic turnovers. Also, with a catalyst consisting of a cyclodextrin linked to a metal ligand carrying a Zn2+ and its bound oxime anion, we saw good catalyzed hydrolysis of bound phenyl esters with what is called burst kinetics (fast acylation, slower deacylation), as is seen with many enzymes [117]. 

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. 

Ikeda, H., Horimoto, Y., Nakata, M., Ueno, A. Artificial holoenzymes for benzoin condensation using thiazolio-appended -cyclodextrin dimers. Tetrahedron Lett. 2000, 41, 6483-6487. 

Breslow and Zhang have reported the cleavage of phosphate di- and triesters by a cyclodextrin dimer (Figure 83) in the presence of La and H2O2 [HO]. High rate acceleration, up to 10 , was reported for this enzyme mimic. 

Surface P-Cyclodextrin dimers linked on the Selective disruption of protein Citrate synthase and L-lactate [100]... 

Leung DK, Yang Z, Breslow R (2000) Selective disruption of protein aggregation by cyclodextrin dimers. Proc Natl Acad Sci USA 97(10) 5050-5053... 

Figure 7.7 Synthetic mimics of a bioreceptor based on cyclodextrin dimer host models [18]. 

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]. 

Mulder A, JuKOvic A, Huskens J, Reinhoudt DN, Bis(phenylthienyl)-ethane-tethered y -cyclodextrin dimers as photoswitchable hosts, Org. 

Noncovalently bound cyclodextrin dimers and related compounds 05KGS1603. 

Figure 2.4 A cyclodextrin dimer that can bind a diester with two hydrophobic ends, and catalyse its hydroiysis as the zinc compiex of the dimer...

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. 

In a later study we examined the ability of cyclodextrin dimers linked by a bipyridyl unit to catalyse the hydrolysis of a phosphate ester, fcw-p-nitrophenyl phosphate. With a bound lanthanum ion the hydrolysis was accelerated by 300 million-fold, a huge acceleration that could well be of practical interest in the hydrolysis of phosphate esters generally. A full paper described this work in some detail. " ... 

One problem with such studies is that p-nitrophenyl acetate is a highly reactive ester, and it is more of a challenge to catalyse the hydrolysis of ordinary esters or of amides. In a move in this direction we showed that an appropriate cyclodextrin dimer with a bound copper ion (8) could indeed catalyse the hydrolysis of an ordinary ester group, not a phenyl ester. " The acceleration was 18,000-fold, certainly a respectable catalytic result... 

Figure 2.8 Doubly-linked cyclodextrin dimers can have both the clamshell geometry - a very strong binder of ditopic substrates - and the loveseat geometry in which a substrate cannot bridge between the two cyclodextrins...

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, Very fast ester hydrolysis by a cyclodextrin dimer with a catalytic linking group, J. Am, Chem. Soc., 1992, 114, 5882-5883. 

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