Enzyme mimics calixarenes

Figure 3.80 Proposal for the use of calixarenes as enzyme mimics. (Reproduced with permission of The Royal Society of Chemistry.)...

One of the principal reasons for the interest in the calixarenes is their potential for serving as enzyme mimics. If they are to operate in this capacity, however, it is necessary that they carry functional groups of various types. The p-ieri-butylcalix-arenes have proved to be excellent precursors for functional group introduction, for the p-tert-butyl group is easily removed by /ram-alkylation 123). As outlined in Scheme 7, de-ieri-butylation of p-terf-butylcalix[4]arene (58) yields compound 59 which is amenable to functionalization in the p-position. For example, bromination of the tetramethyl ether of calix[4]arene (60) proceeds smoothly, affording the tetra-bromo compound 61124) which, by lithiation followed by carbonation yields the... 

Selective functionalization of calixarenes is of central importance for the construction of compounds to serve in various capacities such as polyfunctional ion binders, molecular complexing agents, and enzyme mimics. Many examples of selective functionalization have already been included in the preceding sections, and only a few additional ones are presented in this section as representative of the present state of the art. 

The calixarenes are phenol-formaldehyde cyclic oligomers which possess hydro-phobic cavities capable of forming inclusion complexes with aromatic guest molecules in the solid state [1,2]. They also have the ability to function as ion and molecular carriers as well as enzyme mimics [1, 3,4]. 

This apparent controversy was resolved by the seminal work of David Gutsche who developed reproducible synthetic procedures for the family of vase-like compounds, which in 1975 he called Calixarenes. David became interested in the chemistry of the Zinke compounds because he was a consultant to the Petrolite Corporation that produced surfactants for the oil industry. One of their products was a linear ohgomer obtained from reaction of p-tert-butylphenol and formaldehyde. Problems in the production process led to a detailed study of the reaction and during the more detailed investigations the Petrolite team rediscovered the crystalline Zinke compound. David s personal interest in these macrocyclic molecules was their possible use as platforms for enzyme mimics, in particular the Aldolase catalysis. Although he never realized such an artificial enzyme, David devoted... 

To obtain better catalytic reactivity in the enzyme-based highly selective and demanding reactions, calixarenes are employed as an enzyme-mimic vehicle which introduce hydrophobic environment and residues in the enzyme pocket to stabilize intermediates. The substrate binding pocket, having a substantial role in the reaction kinetics, basically locates next to the metal ion in order to lead substrate to... 

In another enzyme-mimics study invested by Yilmaz et al. [41], caUx[4]arenes bearing imidazole or triazole groups were synthesized in order to investigate their enzymatic performance by applying the MichaeUs-Menten kinetics in the catalytic hydrolysis of p-nitrophenyl acetate (see Fig. 27.21). It was found that the imidazole-functionalized monomeric mimic exhibited higher acyltransferase mimics efficacy than the triazole-functionalized mimic. It was also found that H-bonding sites of calixarenes had a significant effect on catalytic activity. 

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],... 

Because of their unique molecular structure, calixarenes have been used as promising materials which could take a prominent place such as development of mimic biocatalysts, enhancing catalytic activity and enantioselctivity of enzymes, and providing organic/water solubility to the reagents for several enzyme-dependent biological reactions [27-29]. 

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