The calixarenic receptors exhibit remarkable host-guest properties towards biologically relevant guests. Aspects of complex formation reactions between both native and derivatized amino acids, di-and tripeptides with calixarenic (chiral or not) receptors are summarized in this critical review. Thus, the discussions emphasize the parameters that affect the molecular binding selectivity and efficiency of functionalized calix[n]arenes towards these substrates. A brief survey on their application in separation of amino acids is also considered (123 references).

Herein we report the synthesis and characterization of a transporter 9 for N-acetylated amino acids. Transporter 9 is a conjugate of a guanidiniocarbonyl pyrrole cation, one of the most efficient carboxylate binding motifs reported so far, and a hydrophobic tris(dodecylbenzyl) group, which ensures solubility in organic solvents. In its protonated form, 9 binds N-acetylated amino acid carboxylates in wet organic solvents with association constants in the range of 10(4) M(-1) as estimated by extraction experiments. Aromatic amino acids are preferred due to additional cation-pi-interactions of the amino acid side chain with the guanidiniocarbonyl pyrrole moiety. U-tube experiments established efficient transport across a bulk liquid chloroform phase with fluxes approaching 10(-6) mol m(-2) s(-1). In experiments with single substrates, the release rate of the amino acid from the receptor-substrate complex at the interface with the receiving phase is rate determining. In contrast to this, in competition experiments with several substrates, the thermodynamic affinity to 9 becomes decisive. As 9 can only transport anions in its protonated form and has a pK(a) value of approximately 7, pH-driven active transport of amino acids is also possible. Transport occurs as a symport of the amino acid carboxylate and a proton.

The gas-phase recognition of native amino acids and the conformational properties of three glucosylthioureidocalix[4]arenes () were studied theoretically and experimentally using ab initio calculations, ESI-FTICR,(1)H and (13)C NMR MS. The conformational and complexation properties of the glucocalixarenes were dependent on the number of glucose units at the upper rim and the length of the alkyl chains at the lower rim of the calixarene skeleton. ESI-MS experiments showed the compounds to form 1 : 1 complexes with the amino acids, with a marked preference for amino acids containing an aromatic nucleus and an additional H-bonding group in their side chain (Trp, Tyr, Phe >> Ser, Leu and Asp). The experimental data were rationalized by the results of ab initio calculations. ESI-MS competitions carried out with enantiomeric-labelled (EL) amino acids showed enantiomeric selectivities ranging from 0.61 (Phe(D)/Phe(L) with ligand ) to 2.58 (Tyr(D)/Tyr(L) with ligand ). In gas-phase hydrogen-deuterium (H/D) exchange reactions, diglucosylcalix[4]arene exhibited extremely slow exchange rates, which were attributed to the close proximity and strong hydrogen bonding between the facing glucosylthioureido groups. H/D exchange rates were much higher for the tetraglucosylcalix[4]arenes and and their amino acid complexes, and the more rigid tetrapropoxy derivative showed more selective H/D exchange reactions than the calixarene . Bi- or trimodal H/D exchange distribution was observed for the tetraglucosyl derivatives indicating that these ligands exist in multiple isomeric forms in gas phase.

A type of 1,1'-binaphthyl-based imidazolium chemosensor module has been synthesized for the highly selective recognition of tryptophan (Trp) among the eleven alpha-amino acids investigated in aqueous solutions via synergistic effects of multiple hydrogen bonding and electrostatic interactions. These results have demonstrated that the C-2 hydrogen atom of the imidazolium ring plays a key role as a hydrogen bond donor. The UV/vis, fluorescence and mass spectral studies have indicated that a 1 : 1 complex is formed between the host and tryptophan. The binding affinity and selectivity of the cleft-like receptor (R)- with l-Trp are superior to those of (R)-. In spite of an inferior selectivity towards various aromatic amino acids, the macrocyclic (R)- displays a remarkable enantiodiscrimination for the two enantiomers of tryptophan with a K(D)/K(L) value as high as 6.2.

Hydrolytic catalysts were found in a peptidocalixarene library by binding assay with a transition state analogue for the hydrolysis. The rate of the reaction can be specifically enhanced up to 50-fold in the presence of the discovered catalyst.

Calixarenes, macrocyclic compounds of phenolic units linked by methylene groups at the 2,6-positions, present some of the requirements to serve as platforms for the design and synthesis of biological active compounds. They are also interesting host molecules for chemical biology study purposes. Their basic molecular scaffold has potential ability for molecule recognition; it is promptly synthesized in large amounts, and might be easily modified for maximizing molecular interactions toward relevant guest molecules. Calixarenes present well-defined conformational properties and cavities with molecular dimensions that enable to encapsulate guest drugs. Calixarenes have been shown to have antiviral, antibacterial, antifungal, and anticancer activities (including HIV as target). We provide here an overview of the use of calixarenes either as new chemical entity of distinct biological activities or as host for bioactive guest molecules. The importance of calixarenes for drugs development is discussed. The use of Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) techniques for the study of calixarenes as biological molecule hosts is also described.

Nature has devised highly efficient and selective ways of recognizing anionic substrates by using surprisingly few building blocks the most important of which are the amino acids serine, tryptophane, and arginine in addition to NH groups along the protein backbone. Deliberate use of amino acids for the construction of abiotic anion receptors could lead to systems that mimic the anion coordinating properties of anion binding proteins. With this aim in mind several groups have focused their attention on the development of anion receptors containing amino acid building blocks and came up with remarkably efficient systems. This critical review summarizes the different approaches (174 references).

Calix[4]arene-capped [3-(2-O-beta-cyclodextrin)-2-hydroxypropoxy]propylsilyl-appended silica particles (C4CD-HPS), a new type of substituted beta-cyclodextrin-bonded chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC), have been synthesized by treatment of bromoacetate-substituted [3-(2-O-beta-cyclodextrin)-2-hydroxypropoxy]propylsilyl-appended silica particles (BACD-HPS) with calix[4]arene oxyanions in anhydrous N-methyl-2-pyrrolidone. The synthetic stationary phase is characterized by means of elemental analysis. This new type of CSP has a chiral selector with two recognition sites: calix[4]arene and beta-cyclodextrin (beta-CD). The chromatographic behavior of C4CD-HPS was studied with several disubstituted benzenes and some chiral drug compounds under reversed-phase conditions. The results show that C4CD-HPS has excellent selectivity for the separation of aromatic positional isomers and enantiomers of chiral compounds due to the cooperative functioning of calix[4]arenes and beta-CDs.

Four linear thiourea anion receptors (1-3) derived from simple amino acid have been synthesized and their bonding properties with various chiral N-protected amino acid anions were examined by using UV-vis and fluorescence titration experiments. Receptors 1a, 2, and 3 exhibit excellent enantioselective recognition abilities towards N-Boc-protected alanine anion in the UV-vis spectra, obvious difference in the color of solution indicate that the enantiomers of N-Boc-alanine anion could be distinguished by naked eye directly. Receptor 1a is also found to carry out enantioselective fluorescent recognition of the N-acetyl-glutamate.(1)H NMR experiments suggest that hydrogen-bonding interaction between the host and guest is the main factor in the recognition process. Chirality, 2008.(c) 2008 Wiley-Liss, Inc.

The charge neutral chiral optical sensors 1a approximately d containing thiourea and amide groups were synthesized by simple steps in good yields and their structures were characterized by IR,(1)H NMR,(13)C NMR, MS spectra and elemental analysis. The enantioselective recognition for alpha-phenylglycine and phenylglycinol was examined by fluorescence emission and UV-vis spectra. The fluorescence and UV-vis spectra changes of 1a were obvious when the enantiomers of alpha-phenylglycine anion were added, which exhibited that 1a has good enantioselective recognition ability towards alpha-phenylglycine.

The ditopic fluorescent photoinduced electron transfer (PET) amino acid sensory probes and were designed and synthesized from cholic acid. To confer the probes with specific binding ability, an amidothiourea moiety and a cyclic diamino-chiral receptive site were introduced on the C17 side chain and the C7 and C12 hydroxyl pendants, respectively. In acetonitrile, the probes demonstrated differential binding toward trifunctional amino acids like serine, lysine, threonine and tyrosine against other simple amino acids. Enantioselectivities (K(D)/K(L)) of up to 8.9 and sensitivities in the micromolar range with the probes were observed for trifunctional amino acids.