Covalent molecular capsules synthesis

De novo design and synthesis of molecular capsules with appropriate curvatures and complementary binding sites is not an easy task. Covalent modifications on the structure of an already known module are laborious and may encounter unwelcome solubility problems or collapses of concave surfaces. 

A template effect by solvent was found in the synthesis of self-assembled capsules. Experimental evidence shows that the solvent molecules control the covalent bond formation through molecular recognition within the monomeric tetrahedral intermediate. It is proposed that solvation effects can be treated as a subset of molecular recognition events (Tokunaga et al., 1998). 

The synthesis of hollow architectures based on cavitands started in 1985, when Cram et al. reported on the inclusion of solvent molecules in a carcerand obtained by covalent linkage of two cavitands [30]. Since then, molecular and supramolecular capsules have been prepared from cavitands and calix[n]arenes due to two important properties the bowl-shaped form and the various functionalizations which can be introduced at the upper rim of the cavitands or the wider rim of the calix[n]arenes (Fig. 1). 

The encapsulation of chemical space on the scale of simple molecules has been a topic of considerable interest for more than two decades. For the formation of capsules two independent strategies have emerged covalent synthesis and self-assembly. The groups of Cram [8], Collet [9], and Sherman [10] have synthesized capsules capable of encapsulating up to three small molecular guests [11]. Rebek and co-workers pioneered the use of self-assembly to produce a variety of assemblies held together by hydrogen bonds [12-15], Multi-component systems have... 

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