Chirality - the Handedness of Molecules

Isomers Types of isomers in this chapter we study enantiomers and diastereomers

Enantiomers Enantiomers: nonsuperposable mirror images as an example of a molecule that exists as a pair of enantiomers, consider 2-butanol

Enantiomers one way to see that the mirror image of 2-butanol is not superposable on the original is to rotate the mirror image

Enantiomers now try to fit one molecule on top of the other so that all groups and bonds match exactly the original and mirror image are not superposable they are different molecules nonsuperposable mirror images are enantiomers

Enantiomers Objects that are not superposable on their mirror images are chiral (from the Greek: cheir, hand) they show handedness The most common cause of enantiomerism in organic molecules is the presence of a carbon with four different groups bonded to it a carbon with four different groups bonded to it is called a stereocenter

Enantiomers If an object and its mirror image are superposable, they are identical and there is no possibility of enantiomerism such an object is achiral (without chirality) An achiral molecule, consider 2-propanol notice that it has no stereocenter

Enantiomers to see the relationship between the original and its mirror image, rotate the mirror image by 120° after this rotation, we see that all atoms and bonds of the mirror image fit exactly on the original the original and its mirror image are the same

Enantiomers To summarize objects that are nonsuperposable on their mirror images are chiral (they show handedness) among organic molecules, the presence of a carbon with four different groups is the cause of chirality a carbon with four different groups is a stereocenter objects that are superposable on their mirror images are achiral (without chirality) nonsuperposable mirror images are called enantiomers enantiomers always come in pairs

The R,S System Because enantiomers are different compounds, each must have a different name here are the enantiomers of the over-the-counter drug ibuprofen the R,S system is a way to distinguish between enantiomers without having to draw them and point to one or the other

The R,S System The first step in assigning an R or S configuration to a stereocenter is to arrange the groups on the stereocenter in order of priority priority is based on atomic number the higher the atomic number, the higher the priority

The R,S System Example: assign priorities to the groups in each set

The R,S System Example: assign priorities to the groups in each set

The R,S System To assign an R or S configuration 1.assign a priority from 1 (highest) to 4 (lowest) to each group bonded to the stereocenter 2.orient the molecule in space so that the group of lowest priority (4) is directed away from you; 3.read the three groups projecting toward you in order from highest (1) to lowest (3) priority 4. if reading the groups 1-2-3 is clockwise, the configuration is R; if reading them is counterclockwise, the configuration is S

The R,S System example: assign an R or S configuration to each stereocenter

The R,S System example: assign an R or S configuration to each stereocenter

The R,S System returning to our original three-dimensional drawings of the enantiomers of ibuprofen

Two Stereocenters A molecule with n stereocenters has a maximum number of 2n stereoisomers a molecule with one stereocenter, 21 = 2 stereoisomers (enantiomers) are possible for a molecule with two stereocenters, a maximum of 22 = 4 stereoisomers (two pair of enantiomers) for a molecule with three stereocenters, a maximum of 23 = 8 stereoisomers (four pairs of enantiomers) is possible and so forth

Two Stereocenters 2,3,4-trihydroxybutanal two stereocenters; 22 = 4 stereoisomers exist diastereomers: stereoisomers that are not mirror images (a) and (c), for example, are diastereomers

Stereoisomers example: mark all stereocenters in each molecule and tell how many stereoisomers are possible for each

Stereoisomers example: mark all stereocenters in each molecule and tell how many stereoisomers are possible for each solution:

Stereoisomers The 2n rule applies equally well to molecules with three or more stereocenters

Optical Activity Ordinary light: light waves vibrating in all planes perpendicular to its direction of propagation Plane-polarized light: light waves vibrating only in parallel planes Polarimeter: an instrument for measuring the ability of a compound to rotate the plane of plane-polarized light Optically active: showing that a compound rotates the plane of plane-polarized light

Polarimeter

Optical Activity Dextrorotatory: clockwise rotation of the plane of plane-polarized light Levorotatory: counterclockwise rotation of the plane of plane-polarized light Specific rotation: the observed rotation of an optically active substance at a concentration of 1 g/mL in a sample tube 10 cm long

Chirality in Biomolecules Except for inorganic salts and a few low-molecular-weight organic substances, the molecules in living systems, both plant and animal, are chiral although these molecules can exist as a number of stereoisomers, almost invariably only one stereoisomer is found in nature instances do occur in which more than one stereoisomer is found, but these rarely exist together in the same biological system

Chirality in Biomolecules Enzymes (protein bio-catalysts) all have many stereocenters an example is chymotrypsin, an enzyme in the intestines of animals that catalyzes the digestion of proteins chymotrypsin has 251 stereocenters the max number of stereoisomers possible is 2251! only one of these stereoisomers is produced because enzymes are chiral substances, most either produce or react with only substances that match their stereochemical requirements

Chirality in Biomolecules how an enzyme distinguishes between a molecule and its enantiomer

Chirality in Biomolecules a molecule and its enantiomer or one of its diastereomers elicit different physiological responses as we have seen, (S)-ibuprofen is active as a pain and fever reliever, while its R enantiomer is inactive the S enantiomer of naproxen is the active pain reliever, but its R enantiomer is a liver toxin!

Chirality End Chapter 15