Monolayers chiral discrimination

The implications for films cast from mixtures of enantiomers is that diagrams similar to those obtained for phase changes (i.e., melting point, etc.) versus composition for the bulk surfactant may be obtained if a film property is plotted as a function of composition. In the case of enantiomeric mixtures, these monolayer properties should be symmetric about the racemic mixture, and may help to determine whether the associations in the racemic film are homochiral, heterochiral, or ideal. Monolayers cast from non-enantiomeric chiral surfactant mixtures normally will not exhibit this feature. In addition, a systematic study of binary films cast from a mixture of chiral and achiral surfactants may help to determine the limits for chiral discrimination in monolayers doped with an achiral diluent. However, to our knowledge, there has never been any other systematic investigation of the thermodynamic, rheological and mixing properties of chiral monolayers than those reported below from this laboratory. 

When compressed to surface pressures greater than their stability limits (see Table 10), diastereomeric mixtures of /V-(a-methylbenzyl)stearamides with both stearoylalanine and stearoylserine methyl esters provided clear evidence of chiral discrimination. Force-area isotherms at 35°C for homochiral and heterochiral pairs of N-(a-methylbenzyl)stearamide and stearoylalanine methyl ester show differences in both their lift-off and touchdown (the area per molecule where the surface pressure returns to zero on the expansion arm of the isotherm) areas per molecule (Fig. 32). In addition, monolayers of the heterochiral pair could be compressed to lower areas per molecule than monolayers of the homochiral pair. 

The work reviewed here shows that chiral discrimination in mono-layers is probably quite general and can be modulated by variations in the temperature and pH of the aqueous subphase. This property alone renders the many monolayer studies of racemic materials inconclusive for comparison with naturaUy occurring optically active systems (or vice versa). 

Zeelen found the extent of chiral discrimination to be dependent on the type of monomolecular phase that was formed. Thus, racemic and optically active samples displayed identical force-area curves (Fig. 14) when both formed liquid-expanded films, but owed considerably different curves (Fig. 15) under conditions where both samples formed a more highly condensed monolayer. 

In her initial investigation, Lundquist studied the monolayer behavior of racemic and optically active forms of both tetracosan-2-ol and its acetate derivative on 0.0 lA aqueous HCl over a considerable range of temperature (77). In each case, it was possible to demonstrate chiral discrimination between pure enantiomers versus the racemic substance. Furthermore, the extent of enantiomer discrimination was significantly temperature dependent, being enhanced at lower temperatures and frequently disappearing at higher ones. Under favorable conditions of temperature, however, the appearance of the force-area curves could be very sensitive to the optical purity... 

The ability of a chiral molecule to distinguish between the enantiomers of a second (different) chiral molecule was defined in Sect. II as a diastereomer discrimination. This phenomenon may be observed in a mixed monolayer of two chiral surfactants and may also occur when a chiral substance is dissolved in the aqueous subphase under the monolayer of a second chiral substance. As before, examples of such chiral discrimination would not include those whose difference in monolayer behavior results only from the gross structural differences of diastereomers such as the different force-area characteristics exhibited by mixed monolayers of l-oleoyl-2-stearoyl-3-s -phospha-tidylcholine with epimeric steroids (120). The relevant experiment, that of comparing the monolayer behavior of mixed monolayers of cholesterol with enantiomeric phospholipids, has been reported (121). As might be anticipated from our previous discussion of... 

Probably the most interesting and important example of diastere-omer discrimination known to us is part of the body of work conducted by Monica Lundquist, whose enormous contribution to the area of chiral discrimination in monolayers is discussed in Sect. V. In her third paper (79), she demonstrated that Fredga s method of quasi-racemates (33) can be appUed to the two-dimensional organization of chiral surfactants in monolayers. 

Thus, chiral discrimination may be observed that differentiates the force-area curves of the enantiomers of some surfactants from their racemic modifications. Apparent phase changes in the monolayer can be related to parallel behavior in the crystalline state through X-ray diffraction and differential scanning calorimetry. Formation of racemic compounds and quasi-racemates can be observed in some cases. 

Chiral discrimination effects, however, have been demonstrated with amphi-philes containing relatively apolar methyl ester and hydroxy head groups. Comparisons of mixed monolayers and crystals consisting of long-chain... 

Chiral discrimination effects within surface monolayers may also be employed for separating a racemic surface monolayer into domains of uniform chirality which occurs if the S S or R R interaction is more favourable than the S R interaction (homochiral discrimination). Such a two-dimensional resolution was triggered off by the sprinkling of pure enantiomer A -(a-/ -methylben-zyl)stearamide 5 crystals on to the corresponding racemic monolayer. A rapid decrease of surface pressure well below the equilibrium surface pressure of the racemate was observed . This result implies the deposition of / -configured molecules on the added crystals, leaving a partially resolved film which was composed predominantly of 5 -molecules. 

Vollhardt, D., Emrich, G., Gutberlet, T. Fuhrhop, J. -H. (1996). Chiral discrimination and pattern formation in N-dodecylmannonamide monolayers at the air-water interface, Langmuir, 12 5659. 

Figure 10 Images of domains of monolayers of the o-enantiomer, L-enantiomo-, and racemic mixture of A-stearoylserine methyl ester clearing showing chiral discrimination effects. The domains of the enantiomers display unique curvature, and the domain of the racemic mixture shows featnres with both senses of curvature and hence evidence for chiral segregation. Reproduced from Ref. 62. American Chemical Society, 2003, and the figure caption reads as follows Chiral discrimination of the condensed-phase domains of N-stearoyl serine methyl ester monolayers spread on pH 3 water, (a) D-enantiomer (b) L-enantiomer (c) and (d) 1 1 dl racemate. Image size 80 x 80 pm.

In the case of monolayers of the compound A-tetradecyl-y, 5-dihydroxy-pentanoic acid amide (TDHPAA), chiral discrimination effects in the domain structures were observed by BAM. The small, spear-like crystals showed a longer and shorter branch at one end and were seen to be mirror images of each other when the two enantiomers were compared. The racemic mixture formed a symmetric, almost straight and narrow crystallite for its condensed phase. 

In the last decade, many efforts have been devoted to the study of the influence of chiral molecules on the enzymatic processes at the membrane surfaces. V -Acyl-L-and D-amino acid derivatives have been employed as model substances for simulating biomembranes and interfacial processes at biomembrane surfaces [32]. It has been found that chiral monolayers of V -acylamino acid methyl esters on a pure water surface showed that hydrogen bond formation via NH, COOH, and p-hydroxyphenyl groups (i.e., tyrosine side chains) lead to a pronounced chiral discrimination [33,34]. Homochiral (d-d or L-L interactions) and heterochiral (d-l interaction) discrimination can be observed depending on the area per molecule ( min)> which depends on the conformation of the amino acid residue and on the alkyl chain length. 

CHIRAL DISCRIMINATION IN MONOLAYER PACKING OF HEXADE-CANOL-THIOPHOSPHORYL-2-PHENYLGLYCINOL WITH TWO CHIRAL CENTERS IN THE POLAR HEAD-GROUP... 

The four possible stereomers of a chiral surfactant with two asymmetric centers within the polar head group have been synthesized and their absolute configuration determined by X-ray diffraction. One of the diastereomers exhibits a chiral discrimination when spread on water interface the monolayer racemic film undergoes a phase transition from a liquid-expanded towards a liquid-condensed phase upon compression, while the pure enantiomers only have a liquid-expanded phase, as revealed by the measured pressure-area isotherms. The transition pressure-composition diagram indicates that heterochiral interactions are favored. Our results are compared to predictions of Andelman and de Gennes based upon a statistical model. 

CHir purpose was to improve the understanding of molecular interactions in chiral monolayers by introducing a second chiral center in the polar head, with the hope to obtain a better anchorage at the interface and an increase of the chiral discrimination. Moreover, four possible stereomers may be obtained which will allow a more complete study of the relationships between the molecular packing and configurations. 

Both the N- (a-methylbenzy 1) stearamide and phospholipid systems as detailed above proved to be difficult systems with which to work. The inability of N- a-methylbenzy 1)stearamide to form stable monolayers or even to spread from the crystal on anything but very acidic subphases presents a significant technical challenge despite the presence of a chiral headgroup that is unobstructed by other molecular features. On the other hand, the phospholipid surfactants that spread to form stable films both from solution and from their bulk crystals on pure water subphases at ambient temperatures displayed no discernible enantiomeric discrimination in any film property. The chiral functionality on these biomolecules is apparently shielded from intermolecular interactions with other chiral centers to the extent... 

N-Stearoyltyrosine. The case of N-stearoylserine methyl ester illustrates temperature-dependent enantiomeric discrimination in both monolayers spread from solution and in equilibrium with the bulk phase. Although the IIIA isotherms suggested large differences in the intermolecular associations in homochiral and heterochiral films of SSME, there exist chiral systems in which enantiomeric discrimination as exhibited in film compression properties is much more subtle. N-Stearoyltyrosine (STy) is such a system. 

All of the experiments in pure and mixed SSME systems, as well as in the Af-stearoyltyrosine systems, have one common feature, which seems characteristic of chiral molecular recognition in enantiomeric systems and their mixtures enantiomeric discrimination as reflected by monolayer dynamic and equilibrium properties has only been detected when either the racemic or enantiomeric systems have reverted to a tightly packed, presumably quasi-crystalline surface state. Thus far it has not been possible to detect clear enantiomeric discrimination in any fluid or gaseous monolayer state. 

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