1. Chirality Bettelheim, Brown, Campbell and Farrell Chapter 15

2. Isomers Types of chiral stereoisomers –Enantiomers and diastereomers

3. Enantiomers Enantiomers:Enantiomers: nonsuperimposable mirror images –Example: 2-butanol

4. Enantiomers –See if the mirror image of 2-butanol is superimposable on the original by rotating the mirror image

5. Enantiomers –Then try to fit one molecule on top of the other so that all groups and bonds match exactly –If original and mirror image are not superimposable, they are different molecules enantiomers –Nonsuperimposable mirror images are enantiomers

6. Enantiomers chiralObjects 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 a carbon with four different groups bonded to it stereocenter also known as a chiral carbon –a carbon with four different groups bonded to it is called a stereocenter also known as a chiral carbon

7. Enantiomers If an object and its mirror image are superposable, they are identical and there is no possibility of enantiomerism achiral –Identical molecules are achiral (without chirality) Example of achiral molecule: 2-propanol –Notice that it has no stereocenter

8. Enantiomers –To see the relationship between the original and its mirror image, rotate the mirror image by 120° –Can see that all atoms and bonds of the mirror image fit exactly on the original when it is rotated –Thus, original and its mirror image are the same molecule –Just viewed from different perspectives

9. Enantiomers--Summary chiralObjects that are nonsuperposable on their mirror images are chiral (show handedness) –Chiral molecules have a carbon with four different groups bonded to it stereocenter –Carbon with four different groups bonded to it a stereocenter achiral –Objects that are superposable on their mirror images are achiral (without chirality) enantiomers –Nonsuperposable mirror images are called enantiomers –Enantiomers always come in pairs

10. The R,S System –Enantiomers are different compounds and each must have a different name –Example: Enantiomers of ibuprofen –R,S system is a way to distinguish between enantiomers without having to draw them and point to one or the other

11. 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

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13. High priority Low priority

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

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

17. 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; the three groups of higher priority (1-3) then project toward you 3.read the three groups projecting toward you in order from highest (1) to lowest (3) priority R S 4. if reading the groups 1-2-3 is clockwise, the configuration is R; if reading them is counterclockwise, the configuration is S

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

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

21. The R,S System –Look at enantiomers of ibuprofen

22. Two (or more) Stereocenters nFor a molecule with n stereocenters, the maximum number of stereoisomers possible 2 n is 2 n –A molecule with one stereocenter has 2 1 = 2 stereoisomers (one pair of enantiomers) possible –A molecule with two stereocenters has a maximum of 2 2 = 4 possible stereoisomers (two pairs of enantiomers) –A molecule with three stereocenters has a maximum of 2 3 = 8 possible stereoisomers (four pairs of enantiomers) –etc.

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

24. Stereoisomers –Identify all stereocenters in each molecule –How many stereoisomers are possible for each

25. Stereoisomers –Identify all stereocenters in each molecule –How many stereoisomers are possible for each

26. Stereoisomers The 2 n rule also applies to molecules with three or more stereocenters

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

28. Polarimeter

29. Light vibrates in many directions Polarizer— only light in one plane allowed Polarized light rotated by sample Rotated beam Polarized light vibrates in vertical plane

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

32. Chirality in Biomolecules Most molecules in living systems are chiral!! –Exceptions are inorganic salts and a few low- molecular-weight organic substances –Generally, only one stereoisomer found in nature, even though although a number of stereoisomers are possible –Occasionally more than one stereoisomer is found in nature, but these rarely exist together in the same biological system

33. Chirality in Biomolecules Enzymes (protein bio-catalysts) all have many stereocenters –Chymotrypsin is an enzyme in the intestines of animals that catalyzes the digestion of proteins –Chymotrypsin has 251 stereocenters –Maximum number of stereoisomers possible is 2 251 ! –Only one of these stereoisomers is produced and used by any given organism –Enzymes are VERY SPECIFIC –Enzymes either produce or react with only substances that match their chiral requirements

34. Chirality in Biomolecules –An enzyme distinguishes between a molecule and its enantiomer

35. Chirality in Biomolecules –Enantiomers elicit different physiological responses –(S)-ibuprofen is active as a pain and fever reliever, while its R enantiomer is inactive –S enantiomer of naproxen active as pain reliever, but R enantiomer is a liver toxin!