It sometimes happens in organic chemistry that already known compounds are re-examined by researchers to meet challenging new demands, or as interest rises in potential applications. This is the case for the calixarenes: cyclic oligomers obtained at the end of the 19th century by condensing formaldehyde on para-substituted (p-tert-butyl, p-octyl, …) phenolic acids to produce Bakelite.

Non functionalized (‘parent’) calix[n]arenes are macrocyclic platforms consisting of p-tert-butyl-phenol units bridged through their ortho positions by methylene spacers (the degree of condensation, [n], usually ranges from 4 to 8). In the solid state, the basket form of the calix[4]arene molecules, resembling a chalice (hence their name: calixarene, in which the arene suffix stems from the aryl rings they are made of), presents two cavities (Fig. 11.2):

11.2 Parent calixinjarenes of chalice shape.

1. A hydrophilic cavity, delimited by the phenol functions: the ‘narrow rim’;

2. A lipophilic cavity, delimited by the p-tert-butyl groups: the ‘wide rim’.

In the late 1980s, Gutsche’s team investigated the condensation reactions of calixarenes and pointed out the importance of the experimental condi­tions (heat, reaction time, nature and concentration of the basic catalyst) on the product yield and composition (Gutsche, 1989, 1998). At the same time, Izatt et al. (1983, 1985) were the first to test ‘parent’ calix[n]arenes for carrying alkali cations through supported liquid membranes. However, since phenolate base is very strong, caesium transportation only occurred from very basic feeds (pH > 12) and not from nitrate feeds. Furthermore, although the caesium flow increases with [n], the selectivity toward caesium surprisingly increases as [n] decreases. Inclusion of a caesium cation in the lipophilic ‘wide rim’ cavity of the ‘parent’ calix[4]arene (probably because of the small cavity size of its ‘narrow rim’) was later demonstrated by X-ray diffraction studies assuming the existence of specific electrostatic interac­tions between the caesium cation and the negative charge delocalized on the aryl rings of the deprotonated ‘parent’ calix[4]arene (Harrowfield et al., 1991).

Unfortunately, ‘parent’ calix[n]arenes appeared totally inappropriate for developing a process for caesium separation from acidic PUREX raffinates or other acidic nuclear waste streams. Nevertheless, this family of macrocy­clic compounds appeared doubly interesting in the European P&T strategy, because:

• the scalable synthesis of ‘parent’ calix[n]arenes was demonstrated (high production yields could be expected);

• the functionalization of calix[n]arenes (either through the hydroxyl groups at the ‘narrow rim’ or through the p-tert-butyl groups at the ‘wide rim’) could lead to a wide range of chemically substituted mole­cules (Vicens and Bohmer, 1991, Ungaro and Pochini, 1991, Creaven et al., 2008).

1,2 — alternate 1,3 -alternate

11.3 The four main conformations of calix[4]arenes.

If the shape of the ‘parent’ calix[4]arene is actually fixed in the solid state, the rotation freedom in solution of its phenol units around its methylene bridges lets the calix[4]arene molecule adopt various conformations (Cornforth et al., 1955). The four main ones were named by Gutsche as: cone, partial cone, 1,2-alternate, and 1,3-alternate, depending on the number of phenol units that have flipped through the mid-plane of the molecule (Fig. 11.3).

This pre-organization feature of calix[4]arenes has definitely been the driving force for the design of caesium selective ligands, because caesium complexes of functionalized calix[4]arenes were expected to be increasingly stable as the changes (induced by the complexation reaction) in the organi­zation of the substrate (calix[4]arene), receptor (caesium), and solvent, were small (Lein and Cram, 1985). It appeared particularly interesting to block specific conformations of the calix[4]arene platforms in order to ori­entate suitable chemical functions (that is to say functions able to bind to caesium cations) in desired directions to fit the alkali cation inner coordina­tion shell.