Calixarenes amino derivatives

Picolinamide and thiopicolinamide have been introduced on the lower rims of calixarene scaffolds of various sizes in order to study whether the size of the macrocycle, the cooperation and stereochemical disposition of these binding groups affect the efficiency of extraction and selectivity in the actinide/lanthanide separation. Thus, picolinamide conjugates of calix[4]arene 38-40 and those of calix[6]arene 42-44 and of calix[8]arene 45 and 46 have been formed from appropriate amino derivatives of the corresponding calixarenes and picolinic acid pentafluorophenyl ester. The thiopicolinamide analog 41 has been synthesized from 40 and Lawesson s reagent (2005EJO2338). 

Recently the separation of enantiomers by RIfS and SPR using calixarenes with chiral amide residues was demonstrated [19]. Chirasil-Calix (Fig. 7) is well known from capillary GC as a stationary-phase material because of its good thermal and long-term stability. The separation of amino acid derivatives and lactic esters was widely studied [23]. 

In summary, our approach of using cyclopeptides with natural amino acids and 3-aminobenzoic acid subunits for the development of macrocydic receptors has afforded remarkably efficient hosts. The cation affinity of 4b, for example, exceeds that of many calixarene derivatives. Even more interesting is the high anion affinity of 5 in aqueous solution. By introdudng additional functional groups such as car-boxylates to the periphery of the cavity, we recently also obtained cydopeptides that interact with neutral substrates, for example, carbohydrates [25]. Our peptides therefore represent a versatile dass of artificial receptor that should prove useful in supramolecular and bioorganic chemistry. 

Calixarene esters are easily available by alkylation with ethyl bromoacetate and are often used as starting materials for the introduction of chiral groups at the narrow rim. Their aminolysis by chiral amines led to chiral calixarene derivatives in high yields. Water soluble calix[4]arene amino acid derivatives 9a,b obtained in this way, were successfully used as a pseudostationary phase... 

The first examples of urea-containing dimeric capsules were discovered independently by Rebek and Bohmer [165,166]. These are based on calix[4]arene ethers, in which the lower rim ether units help to fix the calixarenes in a cone conformation via intramolecular interactions. Figure 60 shows the generic structure of such systems. Synthetically, the urea calixarenes are readily prepared. The calixarenes are first nitrated, followed by a reduction of these groups into amines. The urea derivatives are fixed to the upper rim by reaction of the p-amino calixarenes with isocyanates. Many systems were studied using differently substituted ureas which contain either short alkyl chains or simple phenyl derivatives. Studies also involved the changing of the lower rim ether substituents. 

Amino-, carboxy-, and sulfonato-calixarenes and the 1,8-naphthol-derived 12 form moderately strong complexes with polycyclic aromatic compounds in aqueous solution (see ref. 1, pp. 180-185), with Xassoc values approaching 10 M" The aminocalixarenes have been shown to be capable of being transported through a liquid membrane. The water soluble j -cyclodextrin-calix[4]arene 281 (for attachment-of jS-cyclodextrin at the lower rim, see ref. 728) forms a complex with 2-p-toluidino-6-naphthalenesulfonate with assoc = 1-53 X 10 M" . The cysteine-substituted calixarenes 282 (n = 4 and... 

The p-sulfonatocalix[n]arenes 4, originally synthesized by Shinkai et al." as water soluble calixarenes for catalytic studies in water solution, were more recently used by Ueoka et alP as catalysts in the specific acid catalyzed methanolysis of A -Ac-L-amino acids (Phe, lyr, Trp, His, Lys, Arg). Rates of methanolysis in the presence of the calix[n] arene catalysts, normalized per sulfonic group, were compared with rates obtained in the presence of the noncyclic analogue p-hydroxybenzenesulfonic add. Rate enhancements - ranging from 12- to 86-fold - relative to control were recorded only in the methanolysis of basic amino acid derivatives (His, Lys, Arg), but neutral amino add derivatives (Phe, Tyr, Trp) responded virtually in the same way to the presence of cyclic and non-cyclic catalyst. Michaelis-Menten kinetics and H NMR spectral evidence pointed to the intermediacy of inclusion complexes of 4 with the protonated form of basic amino acid derivatives, as shown in 5 for the His-4 (n = 4) combination. 

Attachment of chiral substituents to calixarene skeleton is the first, the most straightforward and still the most popular way to constmct chiral calixarenes. In 1979 Gutsche reported the synthesis of the first chiral calixarene by attaching camphorosulfonyl group to p-tBu-calix[8]arene [1]. Nowadays, attachment of virtually any chiral moiety at the selected position is synthetically feasible. However, some chiral groups, due to their availability and versatility, have been particularly widely exploited, for example amino acid derivatives, peptides, carbohydrates, chiral amines and axially chiral groups. 

Calixarenes are the most easily derivatized of the common supramolecular host systems, and tens of thousands of calixarene derivatives have been synthesized. In order to focus this discussion. Sect. 23.2 of this chapter will present selected examples of calixarenes binding to amino acids, peptides, and proteins, with some examples that provide general lessons in calixarene chemistry and biomolec-ular recognition. A Table that serves as an index for all reported equilibrium constants, including solution conditions, is presented at the end of Sect. 23.2. Section 23.3 of the Chapter will report on recent efforts to use calixarenes in both host-guest and scaffold modes as the basis for new biomolecular technologies. 

Calixarene-Derived Binders of Amino Acids, Peptides, and Proteins... 

Zadmard et al. carried on the dimer concept by introducing amino acid or peptide bridges in order to increase hydrogen bonding to the nucleic acid bases [21]. In another approach calixarene derivatives were equipped with acridine moieties, and high affinities were detected between acridine-functionalized calix[4]arenes and CT-DNA by fluorescence titration [22]. 

Hereafter Lu et al. replaced the cationic functionality at the lower rim by a nucleobase. Hybrids between calixarenes and nucleic acid derived compounds have attained more and more attention and will be presented in Sect. 24.4 in more detail. Equally to the amino and guanidino derivatives the uracil calixarene conjugate was used for the interfacial interaction, now specifically via base paring to the complementary nucleoside adenine in the subphase rather than by electrostatic attraction. The same principle was used for the reverse arrangement An adenine calixarene... 

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