Calixarene-Type Molecules

Many complex P/C cages are to be found amongst metaUophosphorus compounds (Chapter 8). 6.22.2 Calixarene-Type Molecules 

---

C. David Gutsche is retired from the position of Robert A. Welch Professor at Texas Christian University. He is a pioneer in the use of calixarenes in systems designed to mimic enzymes. He has prepared numerous calixarene-type molecules, evaluated their host-guest binding abilities, and studied their catalytic potentials [48,49],... 

Calixarenes are cyclophane-type molecules, in which at least four aromatic units are joined via methylene or related groups [9]. It is known that calix[4]arenes with hydroxy groups in the 2-position normally prefer a conelike conformation, however, depending on the substituents a more or less rapid dynamic interconversion with three possible partial cone conformations is possible (Fig. 1) [9, 10]. 

Li" " and Na+ (preferentially Na" ), but not K", Mg or Ca. Molecules such as these, whose cavities can be occupied only by spherical entities, have been called spherands. Other types are calixarenes (e.g., 22). There is significant hydrogen bonding involving the phenolic OH units in [4]calixarenes, but this diminishes as the size of the cavity increases in larger ring calixarenes. There are also calix[4]-arenes, which have been shown to have conformational isomers (see p. 167) in... 

Metalated container molecules can be viewed as a class of compounds that have one or more active metal coordination sites anchored within or next to a molecular cavity (Fig. 2). A range of host systems is capable of forming such structures. The majority of these compounds represent macrocyclic molecules and steri-cally demanding tripod ligands, as for instance calixarenes (42), cyclodextrins (43,44), and trispyrazolylborates (45-48), respectively. In the following, selected types of metalated container molecules and their properties are briefly discussed and where appropriate the foundation papers from relevant earlier work are included. Porphyrin-based hosts and coordination cages with encapsulated metal complexes have been reviewed previously (49-53) and, therefore, only the most recent examples will be described. Thereafter, our work in this field is reported. 

Crystallographic analysis of the 3 C1 complex (Fig. 3a,b) verified the proposed structure where chloride anion is held almost symmetrically by the amidic functions (Cl...HN=2.45 and 2.52 A). It is also evident that there are several close contacts with the aromatic hydrogens of calixarene (ArH...Cl= 3.05, 3.15 A) and metallocene (CH...C1=2.75, 2.95 A) moieties. As the whole structure creates a dimeric form of head-to-tail type, the chloride anion is held by additional HBs of the metallocene unit from the second molecule (CH... Cl= 2.77,2.93 A). 

Scheme 5.17 Synthesis of bis[2]catenanes of type 12c. Instead of the desired a-connections between alkenyl residues belonging to the same calixarene molecule, a p-connection between the two molecules of the dimer 1515 is also possible. This would leave two remote alkenyl groups for a potential p -connection.

Again at the beginning of the 1970 s, other classes of synthetic macrocycles were being investigated, not necessarily in connection with biological problems. For instance, the rich chemistry of Schiff base derivatives (Fig. 4.8) was being developed and yielded the first macrocyclic complexes in 1979 (Fig. 4.9). Another type of interesting macrocyclic molecules are the calixarenes (Fig. 4.8) the history of which can be traced back to the first experiments, in Berlin in 1872, of Adolf von Baeyer (Nobel prize in chemistry in 1905) who treated p-substituted phenols with formaldehyde in the presence of acid or base. 

Fig. 1 Molecular architecture two fascinating nanometer-scale supramolecular species and the corresponding macroscopic counterparts, (a) Resorcarene-calixarene carcerand [7] and the Battistero of Pisa (Italy), (b) Norbomylogous-type compound [8] and the Olina medieval bridge, Modena (Italy). The geometries of the molecules are constructed by molecular mechanics calculations...

Calixarene-A Versatile Host Calixarenes are macrocyclic host molecules made from phenol units finked through methylene bridges. The great freedom to structurally modify calixarenes allows us to create various types of host structures. 

Calixarenes are macrocyclic molecules synthesized with high yield by condensation of appropriate arenes and aldehyde derivatives. Calix means bowF in Latin and Greek, and this phrase reflects the shape of the tetramer, which usually adopts a bowl or beaker-like conformation. Gutsche first introduced the name calixarene for this class of compounds [38]. Several authors have exhaustively reviewed the chemistry and synthetic procedures, which lead to different structural modifications of calixarenes [39-42]. In general, three types of calixarenes derivatives are known first, metacyclophanes (type 1) second, those obtained by condensation of formaldehyde with phenol (type 11), and third, those obtained by reaction with resorcinol (type III) (Scheme 6). The latter modifications are also called resorcarenes to distinguish calixarenes of type III from those of type II. 

Structural studies of two complexes with dimethylformamide (DMF) and dimethylacetamide (DMA) were reported. In the former, three types of solvent molecules are embedded in the crystal lattice first, disordered isolated molecules located just above the cavities formed by the resorcinol units second, clusters of four DMF molecules located between the calixarene layers and third, single DMF molecules located inside the layers close to the alkyl chains. The challenge for solid state NMR is to recognize and locate guest molecules in the lattice. CP/MAS, dipolar dephasing and variable contact-time exper-... 

The functional groups and reactions discussed above have been used to synthesize various molecules consisting of two or more covalently linked calixarene structures . Figure 13 gives a schematic representation of the main types that have been realized. 

In fact, traditional oxygen carrier molecules are dissolved in organic solvents. Only very few works focus on water-soluble carriers, such as Co-histidine which, however, suffers from very short lifetimes [28]. Therefore, a new type of water-soluble of Co-porphyrin with oxygen affinity was developed by Fiamrnengo et al. [43] for the PBM membrane. This novel carrier was based on the assembly of porphyrins with calixarenes. The self-assembly was driven by electrostatic interactions. The oxygen was assumed to complex inside the cavity of the porphyrin-calixarene assembly. Furthermore, the Co of the porphyrin was shielded from the other side by complexation with a nitrogenous base (1-methylimidazole or caffeine). 

---