Reactions Inside Carcerands

Rutgers. The State University of New Jersey, Department of Chemistry and Chemical Biology, 

Molecular container molecules are spherical, hollow hosts with inner cavities that are large enough to accommodate one or more guest molecules. They were developed by Donald J. Cram in the mid 1980s and have been used extensively as molecular reaction flask in order to study the effect of the confinement on reactions involving the encapsulated guest.  

Hemicarceplexes are stabilized by intrinsic and constrictive binding energy. The latter, a physical barrier, is the activation free energy required for a guest to enter the inner cavity and typically amounts to 25-30kcalmol In carceplexes, this barrier is so high that guest escape is impossible without host destraction. Isolated from the bulk phase, the 

Molecular Encapsidation Organic Reactions in Constrained Systems 2010 John Wiley Sons, Ltd 

The synthesis of hemicarcerands and carceplexes is a templated reaction and the proper choice of template molecule, which complements the shape and size of the inner cavity 

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The same approach can be applied to organic chemistry where very labile species can be encapsulated. In this way, species that usually would rapidly decompose or polymerize even at low temperatures can be stored at room temperature, especially when the guest has no chance to escape from its host. To achieve this goal, hemicarcerands have been mostly used, leading to the preparation of cages containing highly reactive species such as 1,3-cyclobutadiene, cycloheptatetraene, or benzyne. This subject is presented in detail in a specially dedicated chapter (Reactions inside Carcerands, Ralf Warmuth). 

A very interesting thermal pericyclic reaction inside the asymmetric carcerand 51 was recently reported by Reinhoudt and co-workers. They studied the extrusion of SO2 and butadiene from incarcerated 3-sulfolene by mass spectrometry (Figure 9.15). " ... 

Shielding and Stabilization. Inclusion compounds may be used as sources and reservoirs of unstable species. The inner phases of inclusion compounds uniquely constrain guest movements, provide a medium for reactions, and shelter molecules that self-destmct in the bulk phase or transform and react under atmospheric conditions. Clathrate hosts have been shown to stabiLhe molecules in unusual conformations that can only be obtained in the host lattice (138) and to stabiLhe free radicals (139) and other reactive species (1) similar to the use of matrix isolation techniques. Inclusion compounds do, however, have the great advantage that they can be used over a relatively wide temperature range. Cyclobutadiene, pursued for over a century has been generated photochemicaHy inside a carcerand container (see (17) Fig. 5) where it is protected from dimerization and from reactants by its surrounding shell (140). 

Studies on the electrochemical behavior of ferrocene encapsulated in the hemi-carcerands 61 and 62, indicated that encapsulation induces substantial changes in the oxidation behavior of the ferrocene subunit [98]. In particular, encapsulated ferrocene exhibits a positive shift of the oxidation potential of c. 120 mV, probably because of the poor solvation of ferrocenium inside the apolar guest cavity. Lower apparent standard rate constants were found for the heterogeneous electron transfer reactions, compared to those found in the uncomplexed ferrocene under identical experimental conditions. This effect may be due to two main contributions (i) the increased effective molecular mass of the electroactive species and (ii) the increased distance of maximum approach of the redox active center to the electrode surface. 

Hemicarcerands were the first molecular containers in which chemical reactions involving encapsulated reactants have been investigated. In this section, some of the advances in inner-phase chemistry are reviewed. Inner-phase reactions may take place either entirely inside the carcerand, where they are influenced by the shape and size of the inner phase, or at the electrostatic inner surface of the hosts with its unusual high inner-phase polarizability. Typically, these reactions involve one or two encapsulated reactants, in which case the host takes over the role of the solvent cage in equivalent condensed phase reactions. Proper solvation is particularly important in reactions involving zwitterionic intermediates or ion pairs. The absence of polar solvent molecules and the hydrophobicity and reduced deformability of the inner... 

Cram made so-called molecular cells by bonding two hemispherical compounds together at their rims, thus forming prisons for whatever is inside. The contents are determined by whatever is in the reaction mixture when the hemispheres are bonded. These cells, or carcerands, will be the potential vehicles for the slow-release delivery of drugs or pesticides. Carcerands can also be little lab-... 

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