Supramolecular Catalysis by Calixarenes

Calixarenes, oligomeric cyclophanes derived from the condensation of phenols with formaldehyde,1,2 have been playing a prominent role in supramolecular catalysis. Key steps in the activity of a supramolecular catalyst are (i) molecular recognition of the substrate(s) and/or reactant(s); (ii) conversion of the bound substrate(s) into products; and (iii) fast release of the product(s) and recycle of the active form of the catalyst followed by turnover. The rational design of supramolecular catalysts capable of achieving significant results in terms of reaction rate and selectivity has undoubtedly been inspired by the admirable properties of enzymes, which have provided chemists with an extraordinary challenge and a standard to be emulated. The success of calixarenes as supramolecular catalysts rests on the extreme versatility of these cyclophanes, which arises from their ability to act as both hosts, with the possible involvement of their molecular cavity in the recognition process, and molecular platforms, thanks to the possibility of introducing by selective derivatization a variety of ligand moieties and functional groups at either rim of the cavity, in diverse mutual geometrical arrangements. Also important is the possibility of a fine control of their conformational properties, together with a residual flexibility of the calixarene scaffold, even when they are suitably preorganized in a fixed cone conformation. Reinhoudt et al.3 pioneered the development of efficient calixarene-based artificial nucleases and introduced the notion of ‘dynamic preorganization’ to describe the capability of calixarenes to guarantee a good compromise between a well-preorganized set of recognition and/or activation moieties in close proximity and a residual flexibility that greatly helps in the dynamic fit of the catalyst to the bound substrate throughout its transformation into the transition state of the reaction. Overall, the several positive features of calixarenes, notably their ability to form host–guest complexes and the possibility of introducing a large variety of functions by means of selective derivatization, make this class of macrocycles most useful for the purpose of multifunctional catalysis, and good candidates to act as enzyme mimics.