Chiral enantioselective sensor

Measurement of circular dichroism can even permit elucidation of relatively small structural changes. CD spectroscopy is also suitable for the solution of specific application-relevant questions. Studies of the sensor properties of chiral dendrimers make use of the fact that complexation of chiral guest molecules induces changes in the CD bands of the host dendrimers. Thus guest-selective chiroptical effects observed in titration experiments with enantiomeric guest molecules give an indication of the potential of the chiral dendrimer to act as an enantioselective sensor [87]. 

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... 

Since in most cases only one enantiomer possesses a desired pharmacological activity, it is necessary to construct enantioselective sensors to improve the quality of analysis due to the high uncertainty obtained in chiral separation by chromatographic techniques.315 For this purpose, enantioselective amperometric biosensors and potentiometric, enantioselective membrane electrodes have been proposed.264 The selection of one sensor from among the electrochemical sensor categories for clinical analysis depends on the complexity of the matrix because the complexity of different biological fluids is not the same. For example, for the determination of T3 and T4 thyroid hormones an amperometric biosensor and two immunosensors have been proposed. The immu-nosensors are more suitable (uncertainty has the minimum value) for direct determination of T3 and T4 thyroid hormones in thyroid than are amperometric biosensors. For the analysis of the same hormones in pharmaceutical products, the uncertainty values are comparable. 

Fig. 5 Examples of quenching enantioselective sensors involving metal ions (a) JV.W -dioxide of the 1,8-diacridylnaphtalene units which can form a scandium(m) complex (b) high enantioselective quenching obtained by the scandium complex of 11 for 2-aminopropanol (reprinted with permission from [64]. Copyright 2008 American Chemical Society) (c) triamino-diamido copper (II) complex (12) (d) Zn (II) complex with terpyridine based chiral ligand (13) (e) chiral oxazoline containing maleimido polymers (14)...

Chi L, Zhao J, James TD (2008) Chiral mono boronic acid as fluorescent enantioselective sensor for mono a-hydroxyl carboxylic acids. J Org Chem 73 4684—4687... 

Xu KX, He YB, Qin HJ et al (2005) Enantioselective recognition by optically active chiral fluorescence sensors bearing amino acid units. Tetrahedron Asymmetry 16 3042-3048... 

The C2-symmetric ligand l,8-bis(3-ieh-butyl-9-acridyl)naphthalene JV,JV -dioxide 89 (Scheme 31) forms a highly fluorescent scandium complex, used as enantioselective sensor for chiral amino acids. This compound allows for the measurement of the total amount as weU as the enantiomeric excess of a variety of amino alcohols at micromolecular concentrations (2006CC4242). The synthesis and an interesting ring-closure reaction of a very similar species are shown in Scheme 70 (see above). 

Another fluorescence-based method for assaying activity and enantioselectivity of synthetic catalysts, specifically in the acylation of chiral alcohols, was recently reported [27]. The idea is to use a molecular sensor that fluoresces upon formation of an acidic product (acetic acid). Adaptation to high-throughput evaluation of enantioselective lipases or esterases needs to be demonstrated. 

The main components of the membrane of the enantioselective, potentiometric electrode are chiral selector and matrix. Selection of the chiral selector may be done accordingly with the stability of the complex formed between the enantiomer and chiral selector on certain medium conditions, e.g., when a certain matrix is used or at a certain pH. Accordingly, a combined multivariate regression and neural networks are proposed for the selection of the best chiral selector for the determination of an enantiomer [17]. The most utilized chiral selectors for EPME construction include crown ethers [18-21], cyclodextrins [22-35], maltodextrins 136-421, antibiotics [43-50] and fullerenes [51,52], The response characteristics of these sensors as well as their enantioselectivity are correlated with the type of matrix used for sensors construction. 

H-NMR studies and analysis of sensor responses in the CD spectrum - after addition of sugar as guest to the dendrocleft host - show that the ability of this dendritic host to enantioselectively recognise monosaccharides decreases with increasing generation number of the dendron surrounding the chiral core unit. 

The prototype of a first fluorescence sensor for enantioselective recognition of chiral amino alcohols was synthesised by Pu et al. by linking phenylacetylene dendrons to an axially chiral binaphthol core unit (see Fig. 4.71) [14c, d, 25],... 

Fig.4 The principle of chiral recognition by gas sensors chiral discrimination by preferential sorption of the enantiomers of N-TFA-alanine methyl ester (N-TFA-Ala-OMe) into enantioselective (R)- and (S)-octyl-Chirasil-Val polymers. The chemical information is transformed into optical signals by the respective transducers...

The calibration curves for the pure R- and S-enantiomers of halodiether B with SPR are shown in Fig. 10. A significant and reproducible difference upon exposure to the optical antipodes was observed as the response of the chiral sensors to the chiral compounds. Enantioselectivity factors a can be determined by dividing the respective signal heights. For a concentration of 20 xgl 1, the a value for SPR is 9.6 ( 0.7). The a values decrease with increasing concentrations, because fewer complexation sites are available for guest molecules. 

However, the particular synthetic requirements in the preparation of conjugated polymers have thus far severely limited the number of similarly hierarchically structured examples. Pu et al. reported different types of conjugated polymers with fixed main-chain chirality containing binaphthyl units in their backbone which exhibited, for example, nonlinear optical activity or were used as enantioselective fluorescent sensors [42—46]. Some chirally substituted poly(thiophene)s were observed to form helical superstructures in solution [47-51], Okamoto and coworkers reported excess helicity in nonchiral, functional poly(phenyl acetylenejs upon supramolecular interactions with chiral additives, and they were able to induce a switch between unordered forms as well as helical forms with opposite helical senses [37, 52, 53]. 

The doubly functionalized calix[4]arene 9, bearing two chiral arms , was prepared recently [48]. This neutral system proved not only to be a good receptor for a-phenylglycine anions, it was also found to display good enantioselectivity towards the L-isomer fCa(L)//< l(D) = 4.76. It was thus proposed by the authors, that this presumably preorganized receptor could function as a chromogenic sensor for nonracemic a-phenylglycine anions. 

Enantioselectivity was introduced especially for use in analysis of pharmaceuticals, where it was found that some pharmaceutical products have a chiral center and only one of the enantiomers exhibits the required pharmacological and pharmacokinetic behavior. The term was introduced first in relation to separation techniques,278 281 and later sensor technology.282... 

The most sensitive enantioselective separation technique is capillary zone electrophoresis. Here, the detectors utilized are not sensitive enough to be able to detect the enantiomers. In the case of sensors, amperometric biosensors have been found to be most sensitive.264 A better enantioselectivity was found for potentiometric, enantioselective membrane electrodes because a direct interaction between the chiral selector and enantiomer occurred.282 285... 

Self-assembled monolayer and layer-by-layer approaches were combined by thermal cross-linking on the surface of a silver electrode in order to develop a MIP-based sensor for the chiral analysis of thyroxine, a thyroid hormone with an amino-acid side chain [53]. The DPASV response peak current was linear to the concentration of thyroxine in the range from 0.010 to 17.2 ng mL" and the achieved detection limit was 0.0060 ng mL. The molecularly Imprinted film displayed absolute enantioselectivity to the template enantiomer and was applied for the determination of thyroxine in aqueous, blood and pharmaceutical samples with no interference from related compounds. 

Xu, L Yang, Y, Wang, Y, and Gao, J. (2009). Chiral salen Mn(III) complex-based enantioselective potentiometric sensor for 1-mandelic acid. Anal. Chim. Acta. 6.53f21.217-221. 

Numerous examples are found in the literature of analyte detection using EAP systems. Arrays of EAPs are used in biomolecular recognition schemes, resulting in devices known as electronic noses and electronic tongues (371-373) that mimic the mammalian sensor receptors. EAPs functionalized to contain polyalkyl ether and crown ether moieties (374-378) or polymerized in the presence of polyelectrolyte dopants (379) have been used to detect a variety of ions (Li+, Na+, K+, Ba +, Mg +, Cs+, Zn +, Cu+, NR4+) (see Fig. 15). EAPs have also been prepared with enantioselectivity toward chiral dopant ions (380,381) and fimctionalized for molecular recognition (382). 

Further analytical applications of glycopeptide antibiotics involve the development of enantioselective poten-tiometric membrane electrodes employed as sensors for chiral drugs. A carbon paste electrode impregnated with vancomycin or teicoplanin was used for detection of 5-flurbiprofen or / -baclofen (Figure 7) with high sensitivity and selectivity." " ... 

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