Chiral artificial receptors

Fig. 2.1.2. Chiral artificial receptors for the recognition of carbohydrates via ionic hydrogen bonds involving anionic acceptors [1].

Molecular recognition, 16 768-811 24 31 at the air-water interface, 16 799-800 artificial receptors for substrate recognition, 16 792-794 charge attraction dominated, 16 779-781 chiral recognition, 16 789-791 hydrogen bond dominated, 16 781-782 at interfaces and surface monolayers, 16 796-801... 

Molecular Recognition. 1,2-Diaminocyclohexane has been often used as a scaffold for the syntheses of chiral host molecules and artificial receptors. Most of the examples relevant to this field may be found in reference 1. 

An emerging area of modem enantioselective analytics is the development of dedicated, target-specific molecular tools that meet the criteria of being robust, high throughput, and specific [105]. Important groups of such tools constitute chiral artificial sensors and receptors as well as polymer-based chiral materials, such as... 

Kuroda Y, Kato Y. Chiral amino acid recognition by a porphyrin-based artificial receptor. J Am Chem Soc 1995 117 10950-8. 

Peptides composed of various coded and noncoded amino acid residues self-assemble to form various types of supramolecular architectures, including supramolecular helices and sheets, nanotubes, nanorods, nanovesicles, and nanofibers. The higher-order self-assembly of supramolecular (3-sheets or supramolecular helices composed of short synthetic acyclic peptides leads to the formation of amyloid-like fibrils. Synthetic cyclic peptides were used in supramolecular chemistry as molecular scaffolding for artificial receptors, so as to host various chiral and achiral ions and other small neutral substrates. Cyclic peptides also self-assemble like their acyclic counterparts to form supramolecular structures, including hollow nanotubes. Self-assembling cyclic peptides can be served as artificial ion channels, and some of them exhibit potential antimicrobial activities against drug-resistant bacteria. 

Kuroda. Y. Kato, Y. Higashioji, T. Hasegawa, J. Kawanami, S. Takahashi, M. Shiraishi, N. Tanabe, K. Ogoshi. H. Chiral amino acid recognition by a porphyrin based artificial receptor. J. Am. Chem. Soc. 1995, 117. 10950. 

Examples of this technique are described for artificial receptors for the alkaloid yohimbine binding peptides obtained from a phage display library [57], for the steroid libraries related to lla-hydroxyprogesterone [58], corticosterone [58] (reported in Fig. 12), and cortisol [59]. A molecularly imprinted polymer working as a synthetic receptor for a series of chiral benzodiazepines [47], artificial receptors for the tricyclic antidepressant drug nortriptyline—obtained by covalent and noncovalent molecular imprinting and studied by capillary liquid chromatography with a simulated combinatorial library [60,61]—were also examined. 

In order to obtain independent evidence for the involvement of the cyclodextrin cavity, fluorescence measurements were carried out for copper(II) ternary complexes with L- or D-tryptophan. In fact, the fluorescence spectrum of tryptophan has already been shown to be sensitive to the polarity of the microenvironment in which it is located and has been used in many studies as a probe for the conformation of proteins and peptides [53]. As for many fluorophores, the indole fluorescence of Trp is quenched by the copper(II) ion this effect has been used as a measure of the stability constants of copper(II) complexes [54, 55]. In a recent work, it has been shown that the fluorescence of dansyl derivatives of amino acids undergo enantioselective fluorescence quenching by chiral copper(n) complexes and that fluorescence measurements can be used for the study of enatioselectivity in the formation of ternary complexes in solution [56]. Bearing this in mind, we performed the same type of experiments by adding increasing amounts of the [Cu(CDhm)] + complex to a solution of D- or L-tryptophan [36]. The fluorescence titration curve shows that the artificial receptor inhibits the indole... 

The cage-type cyclophane furnishes a hydrophobic internal cavity for inclusion of guest molecules and exercises marked chiral discrimination in aqueous media. The host embedded in the bilayer membrane is capable of performing effective molecular recognition as an artificial cell-surface receptor to an extent comparable to that demonstarated by the host alone in aqueous media. 

FIGURE 1-23 Stereoisomers distinguishable by smell and taste in humans, (a) Two stereoisomers of carvone R) carvone (isolated from spearmint oil) has the characteristic fragrance of spearmint (S)-carvone (from caraway seed oil) smells like caraway, (b) Aspartame, the artificial sweetener sold under the trade name NutraSweet, is easily distinguishable by taste receptors from its bitter-tasting stereoisomer, although the two differ only in the configuration at one of the two chiral carbon atoms. 

Nature makes ample use of chirality at both the molecular and supramolecular levels. Examples are known in which two enantiomers have drastically different effects.7 The search for enantioselective artificial host molecules is therefore not only inspired by natural receptors, it is also dictated by the need to distinguish enantiomers in various fields of chemical applications. 

Quite recently we synthesized truly biomimetic receptors which contain, as spacers between crown ether and ammonium units, peptides instead of unnatural spacers as in 14 and IS. Host compounds such as 21 not only discriminate natural peptides by length and sequence, but are capable, in principle, of chiral recognition. They allow one to study in various media the energetics of side-chain interactions in P-sheet-like structures in a systematic way, exemplifying both the practical and the theoretically interesting aspects in the development of artificial peptide receptors. 

Often, the biological difference between enantiomers is one of activity or effectiveness, with no difference in toxicity. Aspartame (NutraSweet), widely used as an artificial sweetener, has two enantiomers. However, one enantiomer has a sweet taste, while the other enantiomer is bitter. This indicates that the receptor sites on our taste buds must be chiral, since they respond differently to the handedness of aspartame enantiomers. This becomes clearer when looking at the properties of the simple sugars. D-Glucose is sweet and nutritious, whereas L-glucose is tasteless and cannot be metabolized by the body. 

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