Complexation kinetics cucurbiturils

In this case, Cucurbituril (53) reveals a number of enzymelike features The reaction exhibits saturation behaviour, it becomes independent of substrate concentration with sufficient amounts of 54 and 55, high concentrations of 54 retard the cycloaddition (substrate inhibition), and release of product 56 from its complex with Cucurbituril (53) is the rate determining step. NMR spectroscopic data suggest that both starting materials of the cycloaddition are hydrogen bonded to the carbonyl groups of 53 with their ammonium moiety and that the reactive substituents extend into the interior of Cucurbituril (53). In this cavity the pericyclic reaction takes place to form the 1,2,3-triazole 56. Kinetic data indicate that the formation of the ternary complex of Cucurbituril (53) with the two starting materials 54 and 55 is not strainless. Since the reaction is still accelerated very much it is assumed that the transition state of the reaction corresponds to the size of the cavity more closely than the substrates. This is a further indication that this case is a useful enzyme model. 

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]. 

Rates for this reaction may easily be measured by disappearance of azide UV absorption. Most importantly, kinetic saturation behavior is noted with sufficient amounts of the reactants cycloaddition velocity becomes independent of substrate concentration. As is familiar from enzyme catalysis, this indicates complete occupancy of all available cucurbituril by reacting species. In actuality, the rate of the catalyzed reaction under conditions of saturation was found to be the same as that for release of the product from cucurbituril. Such a stoichiometric triazole complex was independently prepared and its kinetics of dissociation were examined by the displacement technique previously outlined, giving the identical rate constant of 1.7xl0 s under the standard conditions. (It is not uncommon for product release to be rate-limiting in enzymic reactions). 

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. 

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... 

CB6 units predominate. In contrast, the addition of CBS to a preformed CB6 pseudorotaxane kinetically impaired the formation of the hetero[4]pseudorotaxane, as the CB6 complexes block the access to the central binding site favored by the larger cucurbiturils. 

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