Racemic solutes

A particular point of interest included in these hehcal complexes concerns the chirality. The heUcates obtained from the achiral strands are a racemic mixture of left- and right-handed double heUces (Fig. 34) (202). This special mode of recognition where homochiral supramolecular entities, as a consequence of homochiral self-recognition, result from racemic components is known as optical self-resolution (203). It appears in certain cases from racemic solutions or melts (spontaneous resolution) and is often quoted as one of the possible sources of optical resolution in the biological world. On the other hand, the more commonly found process of heterochiral self-recognition gives rise to a racemic supramolecular assembly of enantio pairs (204). 

These methodologies have been reviewed (22). In both methods, synthesis involves assembly of protected peptide chains, deprotection, purification, and characterization. However, the soHd-phase method, pioneered by Merrifield, dominates the field of peptide chemistry (23). In SPPS, the C-terminal amino acid of the desired peptide is attached to a polymeric soHd support. The addition of amino acids (qv) requires a number of relatively simple steps that are easily automated. Therefore, SPPS contains a number of advantages compared to the solution approach, including fewer solubiUty problems, use of less specialized chemistry, potential for automation, and requirement of relatively less skilled operators (22). Additionally, intermediates are not isolated and purified, and therefore the steps can be carried out more rapidly. Moreover, the SPPS method has been shown to proceed without racemization, whereas in fragment synthesis there is always a potential for racemization. Solution synthesis provides peptides of relatively higher purity however, the addition of hplc methodologies allows for pure peptide products from SPPS as well. 

Another possibility of constructing a chiral membrane system is to prepare a solution of the chiral selector which is retained between two porous membranes, acting as an enantioselective liquid carrier for the transport of one of the enantiomers from the feed solution of the racemate to the receiving side (Fig. 1-5). This system is often referred to as membrane-assisted separation. The selector should not be soluble in the solvent used for the elution of the enantiomers, whose transport is driven by a gradient in concentration or pH between the feed and receiving phases. As a drawback common to all these systems, it should be mentioned that the transport of one enantiomer usually decreases when the enantiomer ratio in the permeate diminishes. Nevertheless, this can be overcome by designing a system where two opposite selectors are used to transport the two enantiomers of a racemic solution simultaneously, as it was already applied in W-tube experiments [171]. 

Fig. 3-9. Preparative HPLC of 100 mg of the test racemate 8 in a single 2 mL injection using a 250 x 4.6 mm i.d. column containing (5)-Glu-(5)-Leu-DNB CSP. Conditions mobile phase ethyl acetate, flowrate 2.0 mL min , UV detection at 380 nm. Injection 2 mL of 50 mg mL racemate solution. Fractions collected before and after the indicated cut point were 98.4 % ee and 97 % ee pure, respectively. (Reprinted with permission from ref. [86]. Copyright 1999, American Chemical Society.)...

Although somewhat more stable than its hexaammine relative, the air-sensitive [Co(en)3]2+ is still substitutionally labile and racemizes rapidly in solution. Chiral discrimination in its (racemic) solutions has been observed in outer sphere electron transfer reactions with optically active oxidants including [Coin(EDTA)], 209,210 [Cr(ox)3]3-,211,212 Co111 oxalate, malonate, and acetylacetonate (acac) complexes.213... 

The method is based on the fact that certain bacteria, fungi, mould or yeast when allowed to grow in a racemic solution, assimilate or consume one of the enantiomers faster than the other. This is why the method is also known as selective assimilation or preferential decomposition. Thus Penicillium glaucum a species of green mould when allowed to grow in ammonium racemate solution consumes the d 0 tartaric acid and leaves the l form, but in a racemic lactic acid it assimilates the l form leaving behind the d form. 

Finally, one should be cautioned that, occasionally, substances form chiral single crystals of nearly racemic composition. For example, hexahelicene crystals grown from racemic solutions apparently undergo spontaneous resolution, displaying the enantiomorphic space group P2[2,2, however, the e.e. in the crystal is only —2%. This material (and probably others as well) has a lamellar, twinned structure in which alternating layers, 20 p,m thick, of optically pure (/ )-( + )-and (M)-( — )-hexahelicene are perfectly aligned to build up the observed crystal (266). 

Another mechanism of chiral amplification that extends over an even larger scale has been reported by Huck et al. [119] The molecule 12-(9 H-thioxantbene-9 -yli-dene-12H-benzo[a]xanthene (Fig. 11.6), which has no chiral center, nevertheless exists, like the helicenes, in two chiral forms defined by their enantiomeric configurations. Consistent with the discussion in Section 11.2.3, a small net handedness (ca. 0.7 %) could be induced in racemic solutions of this molecule by use of ultraviolet CPL. However, introducing 20 wt% of this molecule, which contained a 1.5% chiral excess of one roto-enantiomer, into a nematic phase of liquid crystals produced macroscopic (100 pm) regions of a chiral cholesteric liquid crystal phase. The... 

As a rule, it is profitable to examine first the nonequivalence behavior of the racemic solute, if it is available. In doing so, one readily determines the resonances for which nonequivalence may be observed and the conditions that are optimal for examining a particular pair of resonances. When different sets of solute resonances are closely spaced, maximum nonequivalence is not always desired on first examination, for resonances may cross over one another, making nonequivalence sense determination ambiguous or an e.e. measurement impossible. In the case of highly enriched samples, this experiment becomes imperative, since one must be certain to correctly identify the signal from the minor enantiomer. In the latter case the signal may also be identified by addition of the racemate or the opposite solute enantiomer. 

Mechanical Separation of Crystals. The first instance of resolution was by L. Pasteur who was able to resolve crystals of sodium ammonium tartrate (which recrystallizes in two distinct, nonsuperimposable forms below 2TC). Although this procedure is rarely used, one might be able to seed a racemic solution resulting in only one... 

The sticking phenomena of L-SCMC fines and crystal breakage phenomena affects on optical purity of D-SCMC crystals during growth process. Optical resolution of D-SCMC can be done successfully by careful crystallization in a racemic solution with sodium chloride. 

FIGURE 17.6 Norvancomycin used as the CMPA. Column Hypersil BDS, mobile phase AcN 20mM TEA buffer (pH 5.2) containing 2.0mM norvancomycin (35 65), (A) racemic solution of ketoprofen and (B) (5)-ketoprofen formulation. (Reprinted from Guo, Z.S. et al., J. Pharm. Biomed. Anal., 41, 310, 2006. Copyright Elsevier, 2006. With permission.)... 

Diasteroisomers, also known as geometric isomers, have different relative orientations of their metal-ligand bonds. Enantiomers are stereoisomers whose molecules are nonsuperposable mirror images of each other. Enantiomers have identical chemical and physical properties except for their ability to rotate the plane of polarized light by equal amounts but in opposite directions. A solution of equal parts of an optically active isomer and its enantiomer is known as a racemic solution and has a net rotation of zero. 

From the list of space groups in Table 24 it follows that hexahelicene crystals are apparently chiral. This is also true for crystals of hexahelicene grown from racemic solutions. However, dissolved single crystals of [6] display optical rotations which show only about 2 % enantiomeric excess instead of 100 %. Solid solutions are unlikely in this case (m.p. racemate 231-233°, optically pure [6] 265-267 °C) and ordinary twinning can also be rejected. 

For expanding NMR spectra of aqueous sample solutions, lanthanide salts such as the chlorides, nitrates, or perchlorates of europium and praseodymium are used [103]. In organic solvents, tris-(/ -diketonato)-europium(III) chelates (1) are usually applied [103]. Chiral europium(III) chelates such as tris-(3-tm-butylhydroxymethylene)-D-camphora-to-europium(III) (2) separate the signals of enantiomers in the NMR spectra of racemic solutions [103],... 

Chiral octameric aggregates of serine, as formed from enantiopure or non-racemic solutions and detected by ESI mass spectrometry, were reported by a number of laboratories. It has also been demonstrated that these clusters... 

This analysis was made possible by our ability to measure CPL from racemic solutions of lanthanide complexes through use of circularly polarized excitation [12,45-47]. The varied lifetime of the lanthanide (III) ions allow for some insight concerning the lability of complexes of this type. For example, we have shown that although no CPL is detected in the luminescence from tris-terdentate complexes of Tb(III) and Eu(III) with oxydiacetate (ODA), CPL is observed from DytDPA -, indicating that, indeed, this complex is D3 in aqueous solution, but that only for the short lived Dy(III) ion (x = 20 psec) is the photoprepared enantiomerically-enriched excited state maintained throughout the emission lifetime [45]. 

Preferential crystallization. Preferential crystallization is one of the oldest methods for the resolution of racemates. It involves seeding of the racemate solution with pure crystals of the desired enantiomer which induce the preferential crystallization of that isomer from the solution. The technology is used in the commercial production of a-methyl-L-dopa (7). 

Our hypothesis is that J-aggregates are inherently chiral and exist in aqueous solution as racemate. We anticipate that their enantiomorphic distribution can be altered by vortex action the enantiomer favoured by stirring is deposited on the cuvette wall, the other remains in solution. This is possible because stirring induces a thermodynamic unbalancing in the racemate solution. The situation is complicated because, being a weak thermodynamic force, vortex action competes with other forces, such as, for example, the (stronger) thermodynamic effect exerted by the presence of high concentrations of chiral templates. 

Fig. 36 (a) CD spectra of the inner solution of J-aggregate after 24 h CCW stirring in the dark (solid curve), starting from a racemate solution (see Fig. 32), and of cuvette walls (dashed curve), showing mirror image CD spectra, (b) The results obtained for CW stirring. Modified from [62]... 

Since the crystal of pip-1 is chiral, it should be either of the two enantiomer crystals D and L. The absolute structures of 20 crystals obtained from a soluti containing racemic compounds indicated that 12 crystals are D and 8 are L. Wh seed crystals with one of the enantiomeric structures, D or L, were added to racemic solution, all the crystals showed the same enantiomeric structures as of the seed crystals. The enantiomeric D L ratio of 20 crystals became 20 0. 

For the cobaloxime complex with pyrrolidine as an axial base ligand, the crystalline state reaction was also observed when the crystal was exposed to a xenon lamp. Four kinds of crystals with different R S compositions were prepared. The crystals of pyrr-1 were obtained from the racemic solution. The pyrr-2 crystals were obtained from a solution that has the complex with an R S ratio of 75 25. The crystals of pyrr-3 and pyrr-4 were also obtained from solutions with the R S ratio of 80 20 and 90 10, respectively. The x-ray crystal analysis indicated that the four crystals are isostructural to each other. From solutions with the R S ratio greater than 9 1, pure enantiomeric crystals were obtained, which are not isostructural to the above crystals pyrr-1 to pyrr-4 [40]. 

Both of the racemic crystals of the piperidine and pyrrolidine complexes have chiral space groups before irradiation. The most important requirement for the racemic-to-chiral transformation is that the two molecules with R and S configurations crystallize in a chiral space group. Since the racemic compounds tend to make a pair around an inversion center in the process of crystallization, the racemic crystals, in general, have a center of symmetry. Otherwise, conglomerate crystals may be deposited from a racemic solution. Therefore, only several crystals with chiral space groups have been reported so far [38]. This may be a reason that such a racemic-to-chiral transformation has not been observed till now. 

Chiral Solvating Agent NEA is an effective chiral solvating agent for NMR determination of enantiomeric purity. The combination of enantiomerically pure NEA (3-5 mol excess) and racemic solute causes the NMR spectra of the diastereomerically solvated enantiomers to differ. Since NEA is an efficient hydrogen-bond acceptor, it solvates better if the solute is a hydrogen-bond donor. (R)-(+)-NEA has been used to determine the enantiomeric purity of a variety of substrates. ... 

Chiral ligand-exchange chromatography is based on the formation of diastereomeric ternary complexes that involve a transition metal ion (M), usually copper II a single enantiomer of a chiral molecule (L), usually an amino acid and the eitantiomers of the racemic solute R and S). The diastereomeric mixed chelate complexes formed in this system are represented by the formulas L-M-R and L-M-S. When these complexes have different stabilities, the less stable complex is eluted first, and the enantiomeric solutes are separated. 

Figure 11.28 shows the band profiles obtained with a wide injection of a large sample of a racemic solution of Troger s base on microcrystaUine cellulose triac-etafe, using ethanol as the mobile phase. The experimental profile (symbols) is overlaid on two calculated chromatograms. These profiles were calculated with... 

Figure 11.28 Experimental (symbols) and calculated chromatograms. 6 ml sample of a racemic solution of Troger s base, with C(+) = C(-) = 1.5 g/L. The solid and dotted lines were calculated using the competitive isotherms as predicted by the IAS theory. The dashed line was calculated using the single-component isotherms (i.e., neglecting competition). Reprinted from A. Seidel-Morgenstern and G. Guiochon, Chem. Eng. ScL, 48 (1993) 2787 (Fig. 11).

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