Cucurbituril systems

So far, the studies of cucurbituril described have been thermodynamic investigations, in which factors contributing to the overall stability of molecular complexes have been explored. While bounteous, these only partly address the question of receptor specificity. For example, in biological systems the kinetics of noncovalent interactions, such as between enzymes and substrates, may be of greater consequence. Clearly, the dynamics of molecular recognition deserve additional attention. Cucurbituril provides diverse opportunities in this area [11]. 

The latter number incorporates just the chemical step(s) of formation of triazole within cucurbituril. Since the product release step apparently is at least 100-fold slower than the actual cycloaddition, the net catalytic acceleration should be adjusted downward by that amount. An instructive alternative estimation of kinetic enhancement is to compare the extrapolated limiting rate for cycloaddition within the complex (i.e. cucurbituril saturated with both reactants, k — 1.9xl0 s ) with the uncatalyzed unimolecular transformation of an appropriate bifunctional reference substrate as in Eq. (3) (k, = 2.0x 10 s ). Such a comparison of first-order rate constants shows that the latter reaction is approximately a thousandfold slower than the cucurbituril-engendered transformation. This is attributable to necessity for freezing of internal rotational degrees of freedom that exist in the model system, which are taken care of when cucurbituril aligns the reactants, and concomitantly to an additional consideration which follows. 

Cucurbit [6] uril and increasingly its higher homologues have been used extensively in a variety of host-guest chemistry and nanostructure assemblies. Of particular appeal are rotaxanes and molecular necklaces, mechanically interlocked assemblies of molecules based on CB [6]. Efficient synthesis of ID, 2D and 3D polyrotaxanes and molecular necklaces (cucurbituril beads linked by a macrocyclic molecule string ) has been achieved by a combination of self-assembly and coordination chemistry. We discuss rotaxanes and molecular necklaces in Section 10.7, and cucurbil-based systems are summarised in a recent review.23... 

Looking more at host-guest type systems, the cucurbiturils are often very efficient catalysts in cases where they simultaneously bind two guests, thus increasing effective concentration and changing a bimolecular reaction into a guas/ -unimolecular one. To take one recent example, cucurbit[6]uril (Section 6.2.4) proves to be a very efficient catalyst for the click 1,3-dipolar cycloaddition reaction of an azide with an alkyne, particularly where the substrates are suitable guests for the cavity, as in Scheme 12.20. Cucurbituril binds very effectively to ammonium ions and addition of a small amount... 

Synthetic chemists have applied the concepts of multivalency and cooperativity to supramolecular chemistry to create, for instance, biomimetic receptors able to recognize small molecules (29,30), polysaccharides (31), and DNA (32). Most of these systems are based on calixa[n]arenes (33-35), cucurbituril (CB) (36,37), and cyclodextrine (CD) (38-40) (see Fig. 1), and they represent ideal guests for assembling photoactive species. 

Fig. 1. Schematic representation of some host systems used for host-guest assemblies from left calixarene, cucurbituril, and p-cyclodextrine.

The slow threading kinetics are a result of the high complex stability between cucurbituril and protonated hexane diamine derivatives. Wenz et al. made a very similar observation while studying the threading of various cyclodextrins along a polycationic polymer chain. ° ° Maximum levels of threading were established only after many weeks. They successfully modelled their post-threading system... 

Cucurbit[n]urils (n = 1 and 8) (38) have also been used for the molecular recognition of zwitterionic species in aqueous medium (Figure 16). These systems show a hydrophobic cavity with the urea-type carbonyls pointing to the corresponding entrances. This peculiarity implies binding properties with some resemblance to other cavitands (CDs, calixarenes, or resorcinarenes). The size of the cucurbituril receptor can be controlled by the number of monomers present in the structure, and they are usually named as CBn (with n being the number of repeating units). 

R. Oun, J.A. Plumb, and N.J. Wheate, A cisplatin slow-release hydrogel drug delivery system based on a formulation of the macrocycle cucurbituril, gelatin and polyvinyl alcohol, /. Inorg. Biochem., 134,100-105,2014. 

FIGURE 5.16 LCST systems using host-guest complexation of cucurbituril or pillararene. 

Thus, macrocyclic amphiphiles are reviewed by Huang et al. with respect to cyclodextrins, calixarenes, cucurbiturils and pillararenes [1]. Similarly, Ma and Zhao present biomedical applications of supramolecular systems based on host-guest interactions, with a focus on cyclodextrins, calixarenes and cucurbiturils [2]. Sansone et al. published a review on calixarenes as multivalent ligands for biomolecular recognition [3]. 

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