Receptors, chiral

The term chiral recognition refers to a process m which some chiral receptor or reagent interacts selectively with one of the enantiomers of a chiral molecule Very high levels of chiral recognition are common m biological processes (—) Nicotine for exam pie IS much more toxic than (+) nicotine and (+) adrenaline is more active than (—) adrenaline m constricting blood vessels (—) Thyroxine an ammo acid of the thyroid gland that speeds up metabolism is one of the most widely used of all prescription... 

Section 7 8 Both enantiomers of the same substance are identical m most of then-physical properties The most prominent differences are biological ones such as taste and odor m which the substance interacts with a chiral receptor site m a living system Enantiomers also have important conse quences m medicine m which the two enantiomeric forms of a drug can have much different effects on a patient... 

Fig. 22. Principle of chiral receptor—substrate recognition (a) formation of diastereomeric inclusion complexes (b) three-point interaction model.

As in the previous categories in this section, there are numerous compounds which have been prepared based on a sugar subunit. Examples may be found in Refs. 7,35,42-45, 57, 82-85, 117—121,175,176,193 and 208. Much of the work in these references has been reported by Stoddart and his coworkers, who have pioneered this field. As with the compounds prepared by Cram, the goal was to prepare a chiral receptor for ammonium ions which could be utilized in enzyme model studies. 

The hand-in-glove fit of a chiral substrate into a chiral receptor is relatively straightforward, but it s less obvious how a prochiral substrate can undergo a selective reaction. Take the reaction of ethanol with NAD+ catalyzed by yeast alcohol dehydrogenase. As we saw at the end of Section 9.13, the reaction occurs with exclusive removal of the pro-R hydrogen from ethanol and with addition only to the Re face of the NAD+ carbon. 

The binding specificity for a chiral molecule (like a hand) at a chiral receptor site is only favorable in one way. 

The same is true for the chiral polysiloxanes described here. Their use as stationary phases in gas chromatography allows the calculation of the differences in enthalpy and entropy for the formation of the diaste-reomeric association complexes between chiral receptor and two enantiomers from relative retention time over a wide temperature range. Only the minute amounts of the polysiloxanes required for coating of a glas capillary are necessary for such determinations. From these numbers further conclusions are drawn on the stereochemical and environmental properties required for designing systems of high enantio-selectivity in condensed liquid systems. 

Chirality derived from the readily accessible a-amino acids has been incorporated into the side chains of aza and diaza macrocyclic polyethers. A number of procedures suitable for peptide synthesis have proved (178) to be unsuitable for acylating the relatively unreactive secondary amine groups of aza crown ethers. Eventually, it was discovered that mixed anhydrides of diphenylphos-phinic acid and alkoxycarbonyl-L-alanine derivatives do yield amides, which can be reduced to the corresponding amines, e.g., l-172. By contrast, the corresponding bisamides of diaza-15-crown-S derivatives could not be reduced and so an alternative approach, involving the use of chiral A-chloroacetamido alcohols derived from a-amino acids, has been employed (178) in the synthesis of chiral receptors, such as ll-173 to ll-175, based on this constitution. 

For the application of label-free optical transduction principles like SPR or RIfS, a chiral receptor bound to a transparent polymer layer is required. As various types of these polymers have already been applied to chromatographic separation processes, a substantial wealth of knowledge was achieved during the last few decades. Stationary materials like bonded amide selectors or cyclodextrins were adopted as sensor coatings. Several different applications of these materials in various fields of interest have been reported in the literature [17]. 

Lipodex E [octakis(3-0-butanoyl-2,6-di-0- -pentyl)-y-cyclodextrin] dissolved in a polysiloxane matrix (SE-54) was used as a chiral receptor. The binding strength of the analyte molecules depends on the interaction mech-... 

Table 3.19 Free energy of complexation, (— AG° / kcal mol-1) of neutral and cationic guests (iodide salts) by chiral receptor 3.108 (20 °C, borate buffer, pD = 9, CDC13 solution).50...

For the chiral recognition of sodium salts of 2-aminopropionate the imida-zolium salt 9 was synthesized [35]. There were four chiral receptors synthesized but only 9 based on (-)-ds-myrtanyl imidazole exhibited the yes-no preliminary complexation of both enantiomers of sodium 2-aminopropionates, being able to complex only the (R)-enantiomer. 

In the last two decades, chiral receptors containing amidic functions were designed almost exclusively for binding protected amino acids [49-57], oligopeptides [54,58], and lactic [59], tartaric [60,61] or camphoric acid derivatives [62]. Usually, chiral building blocks such as spirobifluorene [49, 60], binaphthalene [51,57],or amino acid chains containing macrocycles [52-56,58] were employed. An interesting receptor was synthesized via connection of the calix[4]arene moiety with an aza-crown derivative [61]. 

The bioactivity of a drug is the result of interaction with a biological receptor, a protein molecule with a binding site that is also chiral and stereospecific. The interaction of the D isomer of a drug with a chiral receptor site will differ from the interaction of the L isomer with that site. 

B. In nature, a molecule must fit into a chiral receptor, and only one enantiomer usually fits. 

Dinitroazobenzene was used as the fluorescent residue in a chiral receptor molecule that incorporated both a crown ether and calixarene, the structure of which is shown in Figure 15. Formally, this comprises a ditopic cryptand but such a simple nomenclature is clearly inadequate <2004CH1174>. 

A) One ensotiomer fit esslly into chiral receptor jiie to exert H biological effect, but (b) the other cnanttomer can t fit into the ame receptor. 

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