Chain isomers (Figure 6.2(i)) occur because functional groups can branch off from the main carbon backbone. The number of carbon and hydrogen atoms remains the same but the structures are very different.

Figure 6.2 The different forms of structural isomerism. (i) Chain (ii) positional (iii) mixture of chain and positional.

Positional Isomerism

In positional isomers (Figure 6.2(ii)) the structure of the carbon backbone remains the same but the functional groups or side chains are moved around the backbone.

Combinations

It is possible to have a mixture of chain and positional isomerism (Figure 6.2(iii)). Positional isomerism can occur around an aromatic ring (see Figure 5.3, p. 31), hence the need for precise nomenclature.

Stereoisomers

It is at this point that thinking in three dimensions becomes important. Stereoisomers are isomers whose components are connected around the same point, but whose arrangement in space is different.

Entaniomers

Enantiomers are stereoisomers that are mirror images of each other and all thecomponents of the compound radiating from one point are different. The term forthis is chiral. The position of the compound around which this occurs is a chiral centre (see Figures 6.3, and Figures 6.7). Take, for example, natural alanine, which is foundin only one isomeric form: L -alanine ( Figures 6.3). If alanine is produced synthetically, then both forms L and D alanine, are found. This is signifi cant when it comes togiving a patient nutritional supplementation, as the L isomer is more likely to fit intothe receptor site of an enzyme, which explains why natural products are favoured innutritional supplementation.

Figure 6.3 The two isomers of alanine.

• What exactly do D and L mean?

Light normally vibrates in all directions, but if put through a polarizer it will vibrate in only one direction (Figure 6.4(i)). If another polarizer is placed at exactly 90°, no light will get through. You can test this yourself with two pairs of good-quality sunglasses. Line them up, and then turn one through 90°. The lens will appear black because no light is getting through (Figure 6.4 (ii)).

Figure 6.4 The principles of the polarization of light and how optically active solutions can affect it.

If a solution of an optically active isomer is placed in the path of monochrome (one wavelength only) polarized light, then the light will change orientation. To make it visible again, the next polarizer will have to be twisted either clockwise (dextro-rotation) or anticlockwise (laevo-rotation) to see light again (Figure 6.4 (iii)). This is where the notation dextrorotatory (D) and laevorotatory (L) comes from. The notation now being phased in is:

• Dextrorotatory: clockwise – signified by a (+).

• Laevorotatory: anticlockwise – signified by a (−).

It is possible to see both dextrorotatory and laevorotatory compounds in the same solution at the same time. This is known as a racemic mixture. Special equipment used in general analysis employs this characteristic. It is a fast and non-destructive way to see which optic isomer is present in a solution.

All chiral compounds will rotate light (optically active).

Disastereoisomers

• These stereoisomers do not have a mirror image.

• They are characterized by differences in their pharmacological properties.

• E-Z (cis–trans isomerism, geometrical isomerism)

An example of E-Z isomerism is shown in Figure 6.5 in the case of a compound with a double bond (which has already been shown to prevent rotation; see Figure 4.2, p. 22). The only way to make these compounds identical is to break the bond and rotate it, before rejoining the bond again.

Figure 6.5 Limited rotation around a double bond.

This orientation around a bond can have metabolic significance with regards to the structure of a compound and a patient’s health (see Chapter 10, ‘Lipids’, p. 76) because, as diastereoisomers, compounds possess different chemical properties.

In the literature, you will see these types of isomer referred to in two different ways (Figure 6.6). The older terminology of cis and trans is slowly being replaced by E (for cis) and Z (for trans). However, as cis and trans are well known, certainly in the area of fatty acids, as far as the general public is concerned it is useful to be conversant with both.

Figure 6.6 Different forms of an isomer with their old and new style nomenclature.

What Happens When a Compound has More Than One Chiral Centre?

Chemical compounds can have more than one chiral centre. Alpha tocopherol (Figure 6.7) is a good example of this. In this case, the nomenclature S or R is used to denote whether the methyl group is to the left (S) or right (L), respectively, counting from the aromatic end. The other notations of (+) or (−) can also be used for the various types of tocopherol (see Chapter 13 ‘Vitamins and minerals’, p. 107). All natural tocopherol is RRR. Synthetic tocopherol can have SRR, SSR, SRS, SSS, RSR, RRS, RSS and RRR forms, which is why nutritionists stress the use of natural tocopherol.