Molecules chiral

Chiral molecules cannot be superimposed on their mirror images 

Mirror image from above rotated to match up the ethyl (blue) and methyl (green) parts 

In contrast with chiral molecules, such as 2-bromobutane, compounds having structures that are superimposable on their mirror images are achiral. Examples of chiral and achiral molecules are shown above. The first two chiral structures depicted are enantiomers of each other. 

All the chiral examples contain an atom that is connected to four different substituent groups. Such a nucleus is called an asynunetric atom (e.g., asymmetric carbon) or a stereocenter. Centers of this type are sometimes denoted by an asterisk. Molecules with one stereocenter are always chiral. (We shall see in Section 5-6 that structures incorporating more than one such center need not be chiral.) 

Among the natural products shown in Section 4-7, which are chiral and which are achiral Give the number of stereocenters in each case. 

A helical chain such as is easy to recognize, but it is not always such a facile task to identify a chiral compound by attempting to convince oneself that it is, or is not, non-superposable on its mirror image. Symmetry considerations come to our aid a chiral molecular species must lack an improper (S ) axis of symmetry. 

A chiral molecule lacks an improper (S ) axis of symmetry. 

The importance of chirality is clearly seen in, for example, dramatic differences in the activities of different enantiomers of chiral drugs.  

Caner et al. (2004) Drug Discovery Today, vol. 9, p. 105 - Trends in the development of chiral drugs . 

Vj Fig. 4.21 A tetrafluoro derivative of spiropentane which belongs to the 54 point group. This is an example of a molecule that contains no inversion centre and no mirror plane but is, nonetheless, achiral. 

Helical chains such as Se o (Fig. 3.20a) may be right- or left-handed and are chiral. 6-Coordinate complexes such as [Cr(acac)3] ([acac], see Table 7.7) in which there are three bidentate chelating ligands also possess non-super-posable mirror images (Fig. 3.20b). Chiral molecules can rotate the plane of plane-polarized light. This property is known as optical activity and the two mirror images are known as optical isomers or enantiomers. We return to this in Chapter 19. 

Another commonly used criterion for identifying a chiral species is the lack of an inversion centre, i, and plane of 

Basic Terminology of Stereochemistry lUPAC Recommendations 1996 (1996) Pure and Applied Chemistry, vol. 68, p. 2193. 

Another commonly used criterion for identifying a chiral species is the lack of an inversion centre, i, and plane of symmetry, a. However, both of these properties are compatible with the criterion given above, since we can rewrite the symmetry operations i and a in terms of the improper rotations S2 and Si respectively. (See problem 3.25 at the end of the chapter.) However, a word of caution there are a few species that are non-chiral (achiral) despite lacking an inversion centre, i, and plane of symmetry, a. 

Optical activity is observable in any direction for crystals belonging to the two cubic enantiomorphic classes 23 and 432, but, in general, optical activity can only be observed in certain symmetry limited directions. For example, optical activity in the other enantiomorphic classes is only readily observed in a direction fairly close to an optic axis. This is because the different refractive indices that apply to light polarised vertically and horizontally masks the effect in directions further from an optic axis. In the non-enantiomorphic groups, no optical activity is found along an inversion axis or perpendicular to a mirror plane. Thus no optical activity occurs along the optic axis 

Pasteur s crystals of tartaric acid are more complex because the molecules contain two chiral carbon atoms. These can cancel out internally in the molecule so that three molecular forms actually exist, the two optically active mirror image structures that cannot be superimposed on each other, as the laevorota-tory (/-) and dextrorotatory (d-) forms, and the 

Although many optically active crystals contain optically active molecules, this is not mandatory. Crystals of quartz, one variety of silicon dioxide, SiC 2, occur in left or right-handed forms although no molecules are present. The structure of this material is composed of helices of corner-linked Si04 tetrahedra. The direction of the helix determines the left or right-hand nature of the crystals. 

This chapter introduces a new type of stereoisomer, the most subtle that we will encounter. This type of stereoisomer arises because of the tetrahedral geometry of singly bonded carbon. After this stereoisomerism is described, a discussion of how to recognize when these stereoisomers occur is presented. Next, a method to designate the configuration of these stereoisomers is described. After a discussion of when their properties differ, more complex examples are described. Finally, how they are prepared and how they are separated are considered. 

Although you are probably getting better at seeing the three-dimensional shapes of molecules when viewing two-dimensional representations, it is still worthwhile to construct models to help you understand the material in this chapter. And remember to take advantage of the online computer models that are available for the molecules discussed in this chapter. 

Even some fairly simple molecules, such as 2-chlorobutane, exhibit this new type of isomerism just mentioned. The special feature of 2-chlorobutane that causes it to exhibit this type of stereoisomerism is that one of its carbons has four different groups attached to it. 

This carbon has four different groups attached to it, a chlorine, a hydrogen a methyl group, and an ethyl group. 

To see this new type of isomer, we must carefully examine the arrangement of the four groups around this carbon. The following structure shows the arrangement of 

CH2OH Psicose Lyxose Xylose CH2OH Tagatose 

In the preceding chapters, we have looked at isomers. Let s review those now. Molecules are structural isomers when they have the same molecular formula, but different bonding arrangements. 

Another group of isomers called stereoisomers has identical molecular formulas, too, but they are not structural isomers. In stereoisomers, the atoms are bonded in the same sequence but differ in the way they are arranged in space. 

Identify chiral and achiral carbon atoms in an organic molecule. 

FIGURE 13.2 The left and right hands are chiral because they have mirror images that cannot be superimposed on each other. 

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Marquardt R and Quack M 1996 Radiative excitation of the harmonic oscillator with applications to stereomutation in chiral molecules Z. Rhys. D 36 229-37... 

Quack M 1989 Structure and dynamics of chiral molecules Angew. Chem. Int. Ed. Engl. 28 571-86... 

An important distinction among surfaces and interfaces is whether or not they exliibit mirror synnnetry about a plane nonnal to the surface. This synnnetry is particularly relevant for the case of isotropic surfaces (co-synnnetry), i.e. ones that are equivalent in every azunuthal direction. Those surfaces that fail to exliibit mirror synnnetry may be tenned chiral surfaces. They would be expected, for example, at the boundary of a liquid comprised of chiral molecules. Magnetized surfaces of isotropic media may also exliibit this synnnetry. (For a review of SFIG studies of chiral interfaces, the reader is referred to [68]. ... 

Given the interest and importance of chiral molecules, there has been considerable activity in investigating die corresponding chiral surfaces [, and 70]. From the point of view of perfomiing surface and interface spectroscopy with nonlinear optics, we must first examhie the nonlinear response of tlie bulk liquid. Clearly, a chiral liquid lacks inversion synnnetry. As such, it may be expected to have a strong (dipole-allowed) second-order nonlinear response. This is indeed true in the general case of SFG [71]. For SHG, however, the pemiutation synnnetry for the last two indices of the nonlinear susceptibility tensor combined with the... 

A schematic diagram of the surface of a liquid of non-chiral (a) and chiral molecules (b) is shown in figure Bl.5.8. Case (a) corresponds to oom-synnnetry (isotropic with a mirror plane) and case (b) to oo-symmetry (isotropic). For the crj/ -synnnetry, the SH signal for the polarization configurations of s-m/s-out and p-m/s-out vanish. From table Bl.5.1. we find, however, that for the co-synnnetry, an extra independent nonlinear susceptibility element, is present for SHG. Because of this extra element, the SH signal for... 

As witli tlie nematic phase, a chiral version of tlie smectic C phase has been observed and is denoted SniC. In tliis phase, tlie director rotates around tlie cone generated by tlie tilt angle [9,32]. This phase is helielectric, i.e. tlie spontaneous polarization induced by dipolar ordering (transverse to tlie molecular long axis) rotates around a helix. However, if tlie helix is unwound by external forces such as surface interactions, or electric fields or by compensating tlie pitch in a mixture, so tliat it becomes infinite, tlie phase becomes ferroelectric. This is tlie basis of ferroelectric liquid crystal displays (section C2.2.4.4). If tliere is an alternation in polarization direction between layers tlie phase can be ferrielectric or antiferroelectric. A smectic A phase foniied by chiral molecules is sometimes denoted SiiiA, altliough, due to the untilted symmetry of tlie phase, it is not itself chiral. This notation is strictly incorrect because tlie asterisk should be used to indicate the chirality of tlie phase and not tliat of tlie constituent molecules. 

The polymers described so far have relatively flexible main chains which can result in complex confonnations. In some cases, tliey can double back and cross over tliemselves. There are also investigations on polymers which are constrained to remain in a confonnation corresponding, at least approximately, to a straight line, but which have amphiphilic properties tliat ensure tliat tliis line is parallel to tire water surface. Chiral molecules are one example and many polypeptides fall into tliis class [107]. Another example is cofacial phtlialocyanine polymers (figure C2.4.9). 

Figure 2-70. Examples of chiral molecules with different types of stereogenic units.

The Cahn-Ingold-Prelog (CIP) rules stand as the official way to specify chirahty of molecular structures [35, 36] (see also Section 2.8), but can we measure the chirality of a chiral molecule. Can one say that one structure is more chiral than another. These questions are associated in a chemist s mind with some of the experimentally observed properties of chiral compounds. For example, the racemic mixture of one pail of specific enantiomers may be more clearly separated in a given chiral chromatographic system than the racemic mixture of another compound. Or, the difference in pharmacological properties for a particular pair of enantiomers may be greater than for another pair. Or, one chiral compound may rotate the plane of polarized light more than another. Several theoretical quantitative measures of chirality have been developed and have been reviewed elsewhere [37-40]. 

In most common chiral molecules, chirality arises from chiral tetravalent atoms. A conformation-independent chirality code (CICC) was developed that encodes the molecular chirality originating from a chiral tetravalent atom [42], For more generality, a conformation-dependent chirality code (CDCC) is used [43]. CDCC ti cats a molecule as a rigid set of points (atoms) linked by bonds, and it accounts for chirality generated by chirality centers, chirality axes, or chirality planes. 

Only reaction 1 provides a direct pathway to this chiral molecule the intermediate 2-methyl-butanal may be silylated and reacted with formaldehyde in the presence of the boronated tartaric ester described on page 61. The enantiomeric excess may, however, be low. 

Achiral molecules which can be converted to chiral molecules by the chemical change of one atom — substitution on an sp -atom or addition on an sp -atom — are called prochiral molecules (Y. Izumi, 1977). The atom involved is a prochiral centre. Pairs of atorns or groups... 

One final very important point Everything we have said in this section concerns molecules that have one and only one chirality center molecules with more than one chirality center may or may not be chiral Molecules that have more than one chirality center will be discussed m Sections 7 10 through 7 13... 

Whal causes oplical rolalion" The plane of polanzalion of a lighl wave undergoes a minute rolalion when il encounters a chiral molecule Enanliomenc forms of a chiral molecule cause a rolalion of Ihe plane of polarizalion m exaclly equal amounls bul m... 

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... 

As the experimental tools for biochemical transformations have become more pow erful and procedures for carrying out these transformations m the laboratory more rou tine the application of biochemical processes to mainstream organic chemical tasks including the production of enantiomerically pure chiral molecules has grown... 

Section 7 2 The most common kind of chiral molecule contains a carbon atom that bears four different atoms or groups Such an atom is called a chirality center Table 7 2 shows the enantiomers of 2 chlorobutane C 2 is a chi rahty center m 2 chlorobutane... 

The enzyme is a single enantiomer of a chiral molecule and binds the coenzyme and substrate m such a way that hydride is transferred exclusively to the face of the carbonyl group that leads to (5) (+) lactic acid Reduction of pyruvic acid m the absence of an enzyme however say with sodium borohydride also gives lactic acid but as a racemic mixture containing equal quantities of the R and S enantiomers... 

Each act of proton abstraction from the a carbon converts a chiral molecule to an achi ral enol or enolate ion The sp hybridized carbon that is the chirality center m the start mg ketone becomes sp hybridized m the enol or enolate Careful kinetic studies have established that the rate of loss of optical activity of sec butyl phenyl ketone is equal to Its rate of hydrogen-deuterium exchange its rate of brommation and its rate of lodma tion In each case the rate determining step is conversion of the starting ketone to the enol or enolate anion... 

Techniques for determining the absolute configuration of chiral molecules were not developed until the 1950s and so it was not possible for Eischer and his contemporaries to relate the sign of rotation of any substance to its absolute configuration A system evolved based on the arbitrary assumption later shown to be correct that the enantiomers... 

A chiral molecule is one which exists in two forms, known as enantiomers. Each of the enantiomers is optically active, which means that they can rotate the plane of plane-polarized light. The enantiomer that rotates the plane to the right (clockwise) has been called the d (or dextro) form and the one that rotates it to the left (anticlockwise) the I (or laevo) form. Nowadays, it is more usual to refer to the d and I forms as the ( + ) and (—) forms, respectively. 

Very often, a sample of a chiral molecule exists as an equimolar mixture of (+) and (—) enantiomers. Such a mixture will not rotate the plane of plane-polarized light and is called a... 

If a molecule is not superimposable on its mirror image then it is a chiral molecule. 

We have seen in Section 4.1.4 that = n and that S2 = i, so we can immediately exclude from chirality any molecule having a plane of symmetry or a centre of inversion. The condition that a chiral molecule may not have a plane of symmetry or a centre of inversion is sufficient in nearly all cases to decide whether a molecule is chiral. We have to go to a rather unusual molecule, such as the tetrafluorospiropentane, shown in Figure 4.8, to find a case where there is no a or i element of symmetry but there is a higher-fold S element. In this molecule the two three-membered carbon rings are mutually perpendicular, and the pairs of fluorine atoms on each end of the molecule are trans to each other. There is an 54 axis, as shown in Figure 4.8, but no a or i element, and therefore the molecule is not chiral. 

In Section 4.2.1 it will be pointed out that hydrogen peroxide (Figure 4.1 la) has only one symmetry element, a C2 axis, and is therefore a chiral molecule although the enantiomers have never been separated. The complex ion [Co(ethylenediamine)3], discussed in Section 4.2.4 and shown in Figure 4.11(f), is also chiral, having only a C3 axis and three C2 axes. 

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