objectives

Stereochemistry of amino acids

Amino acids are optically active

Recall from B2 that amino acids consist of a carbon bonded to an amino group, a carboxyl group, a hydrogen and a variable 'R' group. With the exception of glycine (whose R group is hydrogen), all of the amino acids contain a chiral centre, a carbon that is bonded to four different substituents.

Chiral centres in a compound are the requirement for optical isomerism. Optical isomers are one type of stereoisomer that are capable of rotating plane polarised light. The two isomers are known as enantiomers. Enantiomers are molecules that have the same chemical formula, but different arrangements in three-dimensional space. They are mirror images of each other that cannot be superimposed.

A polarimeter is used to distinguish one enantiomer from the other. When a pure sample of a single enantiomer is present, the light will rotate in one direction. When a pure sample of the other enantiomer is present, light will rotate in the opposite direction by the same magnitude. A sample where both enantiomers are present will have a smaller angle of rotation, compared to a pure sample, so the angle of rotation can also be used to analyse the purity of a sample. A mixture containing an equal proportion of both enantiomers, called a racemic mixture, will result in no optical rotation.

Optical rotation is designated as 'd-' for dextrorotary (dexter is Latin for right) or 'l-' for levorotary (laevus is Latin for left). Since optical rotation can only be determined experimentally, other systems of assigning notation to enantiomers based on the spatial orientation of the four substituents around the chiral carbon atom have been developed.

The CO-R-N rule

Identifying enantiomers on the basis of spatial arrangement is a system that was developed based on the sugar glyceraldehyde. Glyceraldehyde (C3H6O3) is a triose sugar consisting of three carbons, only one of which is chiral. When glyceraldehyde is oriented such that the hydrogen substituent is placed away from the viewer, shown in three-dimensional notation as dashed lines, the orientation of the three other substituents – the carboxyl group (CO), the R group (R) and the amino group (N) – is then evaluated. If these three groups are counter-clockwise, the amino acid is designated as the L- enantiomer. If these three groups are clockwise, the amino acid is designated as the D- enantiomer.

Interestingly, all naturally synthesised amino acids found in proteins, with the exception of the achiral glycine, are the L-enantiomer. The optical activity of amino acids, however, can vary with some rotating light clockwise and other amino acids rotating counter-clockwise. There is no way to determine the direction of optical rotation from the structure, only experimentally by using a polarimeter, so the D- and L- system of notation is preferred over systems that involve optical rotation.

There are a few instances of naturally occurring D- amino acids; however, they are only seen as free amino acids and not incorporated into proteins. D-glutamic acid and D-alanine are found in the cell walls of certain bacteria. D- amino acids are also found in the venom of certain species including the platypus and cone snail.

Stereochemistry of lipids

As discussed in B3, lipids are made up of fatty acid chains that can contain points of unsaturation – that is, one or more carbon-carbon double bonds. When C=C bonds occur on a hydrocarbon chain, they can either be in the cis or trans orientation. Cis/trans isomers are a type of stereoisomer that exists because the carbon-carbon double bond does not have free rotation, as is seen with single bonds. This results in neighbouring carbon atoms that are either on the same side (cis) or opposite side (trans) of the carbon-carbon double bond.

Naturally occurring unsaturated fatty acids are mostly in the cis configuration, very rarely in the trans form. Recall that saturated fatty acids are linear, while unsaturated fatty acids have a 'kink' in the chain.

In the cis form, C=C causes the fatty acid to bend significantly, reducing the strength of the London dispersion forces with other fatty acid chains, lowering the melting point. In the trans form, the C=C is more linear, almost like a saturated fatty acid chain. This maintains the London dispersion forces with other fatty acid chains, keeping the melting point closer to that of saturated fatty acids.

Food processing

Trans fats occur rarely in nature, but are produced in large quantities in the processing of foods. The hydrogenation of vegetable oils is a process that occurs to make an unsaturated oil into a saturated fat by adding hydrogen gas to a polyunsaturated fatty acid in the presence of a nickel catalyst by a reduction reaction. Hydrogenation is the process used to make margarine and vegetable shortening, both solid fats made from liquid vegetable oils.

Hydrogenation is done for a variety of reasons. A solid fat has a better taste and 'mouthfeel' in products than a liquid oil, which pleases consumers. Solid fats made from vegetable oils can also be less expensive than using naturally occurring solid fats, such as butter. Another reason for hydrogenation is that unsaturated fats are more susceptible to oxidative rancidity. When a fatty acid is fully saturated, there are no carbon-carbon double bonds to react with oxygen, forming a variety of products including ketones and aldehydes that have an unpleasant aroma, indicating that the fatty acid has spoiled. Food producers use hydrogenated fats in order to increase the shelf-life of products, saving costs.

When polyunsaturated fatty acids are hydrogenated, complete hydrogenation can occur, where all carbon-carbon double bonds react with hydrogen, forming a saturated fatty acid. However, partial hydrogenation can also occur, where some carbon-carbon double bonds remain, forming an unsaturated fatty acid. When partial hydrogenation occurs, isomerisation involving the nickel catalyst occurs where the cis double bonds are converted into trans double bonds. Trans fats are more linear than cis fats; therefore, trans fats resemble saturated fats in structure and function. Consuming high levels of trans fats also results in higher blood cholesterol levels, increasing the risk of heart disease.

Stereochemistry of sugars

Monosaccharides

D- and L- sugars

Like amino acids, sugar molecules often contain one or more chiral carbon atoms, giving them optical activity. Sugar molecules can be classified as d- (dextrorotary) or l- (levorotary), depending on how they rotate plane polarised light. However, the D- and L- notation for enantiomers is preferred as experimental optical activity is not required. Interestingly, most naturally occurring sugars are in the D- form.

Glyceraldehyde, C3H6O3, was the sugar upon which the D/L system of notation was developed by Emil Fischer. Using this small triose sugar containing only one chiral centre, he observed the optical activity of each enantiomer and related it to the spatial orientation of the four substituents around the chiral carbon atom. All other molecules are compared to glyceraldehyde for this naming convention.

Emil Fischer developed his own projection model for this system. When the chiral carbon is oriented with the hydrogen facing away from the viewer, the molecule is rotated such that the two substituents that are pointing towards the viewer are drawn horizontally and the two substituents that are pointing away from the viewer are arranged vertically. This makes the Fischer projection for a straight chain sugar.

For glyceraldehyde, the two enantiomers have mirror image Fischer projections. If the hydroxyl group is on the right, the enantiomer is designated as D. If the hydroxyl group is on the left, then the enantiomer is L.

Sugars larger than three carbons often have more than one chiral centre. In a Fischer projection, the aldehyde or ketone group is always positioned at the top. The enantiomer is designated based on the orientation of the substituents on the chiral carbon farthest from the aldehyde or ketone group, relative to glyceraldehyde.

α and β sugars

Recall from B4 that sugars undergo cyclisation in aqueous solutions. When a sugar cyclises, it converts to a ring structure that introduces an additional chiral carbon. The cyclisation occurs when the aldehyde or ketone carbon, known as an anomeric carbon, which is not chiral, undergoes a condensation reaction with a hydroxyl group further down the chain. There are two different spatial orientations in which the bond forms, leading to two different enantiomers for the newly formed chiral carbon. This process is known as anomerisation.

There are two different ways in which the cyclisation can occur, forming two different enantiomers, referred to as alpha (α) or beta (β). Using the cyclic Haworth Projection, the alpha enantiomer contains the hydroxyl group below the plane of the ring (pointed downward), while the beta enantiomer contains the hydroxyl group above the plane of the ring (pointed upward). Many sugars, including glucose and fructose, cyclise forming both anomers equally.

Polysaccharides

When one or more monosaccharides undergo a condensation reaction to form a di or polysaccheride, the stereochemistry of the monomers affects the stereochemistry of the polymer. Specifically, when D-glucose molecules polymerise, they give rise to two distinct polymers with very different chemical and physical properties, depending on the stereochemistry of the anomeric carbon.

Starch

Recall that starch, also known as amylose, is the polysaccharide easily absorbed and metabolised by animals as an immediate energy source. Starch is made from α-glucose monomers bonded together. The bond is formed between carbon-1 in one monomer and carbon-4 in the next monomer, forming an α-1,4 glycosidic linkage. In this arrangement, the polysaccharide consists of a slightly coiled linear chain with very few or no branches and high water solubility. Starch is produced during photosynthesis by plants and stored in a semi-crystalline form in starch grains within the plant.

Enzymes in the body, known as amylases, easily recognise the starch polymer and are capable of hydrolysing the starch into individual α-glucose monomers. The glucose can then be metabolised for immediate energy use by cells during cellular respiration or converted to glycogen for storage. Glycogen is a polymer of α-glucose monomers, but connected differently so that there are branched chains, making the molecule more dense and easier to store.

Cellulose

Recall that cellulose is the polymer of glucose that cannot be digested by most animals. Cellulose is made from β-glucose monomers bonded together. As with starch, the bond is formed between carbon-1 in one monomer and carbon-4 in the next monomer, forming a β-1,4-glycosidic linkage. In this arrangement, the glucose molecules must have an alternating arrangement (every other one is flipped). This makes for a polysaccharide that consists of a very straight linear chain with no branches and lower polarity than starch. Cellulose is also produced during photosynthesis by plants and used as a structural component of cell walls for the plant.

Multiple cellulose strands are held together with strong hydrogen bonds, forming strong bundles known as microfibrils. Microfibrils are important for the structure of the plant, allowing it to reach higher elevations in order to absorb sufficient sunlight for photosynthesis. Vascular tissues in plants are also made of strong cellulose fibres that are needed to transport water and minerals upward from the roots to the leaves for photosynthesis and to transport the newly made starch downward from the leaves to the rest of the plant.

Humans lack the enzyme necessary for hydrolysing cellulose into its individual monomers, therefore it cannot be used as a source of energy. Some bacteria contain cellulase enzymes that are capable of hydrolysing and digesting cellulose, including some bacteria that are found in the digestive tract of certain animals, like cows and beavers, allowing these animals to make use of cellulose as an energy source.

Even though many animals, including humans, are not capable of digesting cellulose, it plays an important role in digestive health. Cellulose, also known as dietary fibre, is needed in the diet to keep the digestive tract clean and the contents moving. Since cellulose does not provide any energy, it does not contribute to weight gain, so a diet high in fibre is thought to also help with obesity. A diet low in fibre is associated with certain health risks including constipation, diabetes and high cholesterol.

Stereochemistry of retinal

How the eye works

When light enters the eye through the pupil, it travels through the eye until it hits the back of the eye, the retina. The retina contains specialised photoreceptor cells, called rods and cones, that are responsible for absorbing light and transferring the information to the optic nerve. This information is then transmitted to the brain, which makes sense of what we have seen. The first step of this process is for the rods and cones to absorb light. Rods interpret the intensity of light, whereas cones interpret the colour. There are three types of cone cells that each detect the colours red, blue and green.

As discussed in B5, the interaction of light with vitamin a compounds in the eye plays a role in vision. A diet that is deficient in vitamin A compounds can result in poor vision or even blindness.

Vitamin A and vision

Vitamin A compounds include retinol, retinal, retinoic acid and carotenoids. The structure of these compounds generally consists of a cyclic ring and a long polyunsaturated hydrocarbon chain, which is a conjugated system. The carbon-carbon double bonds can be found in the cis or trans conformations.

Retinal, also known as retinaldehyde, is ingested in the diet or synthesised from carotenoids. Retinal can then be converted into the other vitamin A compounds – retinol or retinoic acid.

Retinal binds to proteins found in the retina, called opsins. Opsins are light-sensitive proteins found in the rod and cone cells of the retina. Opsins bind to 11-cis-retinal, a vitamin A compound. There are several types of opsin proteins, but one specifically, rhodopsin, is particularly important for vision in humans. Rhodopsin is a complex of an opsin protein bound to 11-cis-retinal. 11-cis-retinal contains all carbon-carbon double bonds in the trans configuration with the exception of one carbon-carbon double bond in the cis conformation, numbered as carbon-11.

When light is absorbed, the 11-cis-retinal is isomerised to all-trans-retinal, making all carbon-carbon double bonds in the trans configuration. This conversion from cis to trans also results in a change in the shape of the retinal from having a bent shape at the location of carbon-11 in the cis configuration to a more linear structure in the trans configuration. Since the shape of retinal is changing, the shape of the rhodopsin protein also undergoes a change.

The isomerisation of retinal triggers a nerve response, which is then propagated to the optic nerve and on to the brain. The rhodopsin then breaks down. Enzymes convert the all-trans-retinal back into 11-cis-retinal so that it can bind to a new opsin protein, regenerating rhodopsin and the cycle can repeat itself. The relationship between the isomers of retinal, opsin and rhodopsin make the visual cycle.