General, Organic, and Biochemistry, 7e

1. General, Organic, and Biochemistry, 7e Bettelheim, Brown, and March

2. Chapter 15 Chirality - the Handedness of Molecules

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

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

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

6. 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

7. 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

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

9. Enantiomers • to see the relationship between the original and its mirror image, rotate the mirror image by 120° • when we do this rotation, we see that all atoms and bonds of the mirror image fit exactly on the original • this means that the original and its mirror image are the same molecule • they are just viewed from different perspectives

10. Enantiomers • To summarize • objects that are nonsuperposable on their mirror images are chiral (they show handedness) • the most common cause of chirality among organic molecules is the presence of a carbon with four different groups bonded to it • we call a carbon with four different groups bonded to it 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

11. 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

12. 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

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

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

16. 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 4. if reading the groups 1-2-3 is clockwise, the configuration is R; if reading them is counterclockwise, the configuration is S

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

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

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

20. Two Stereocenters • For a molecule with n stereocenters, the maximum number of stereoisomers possible is 2n • we have already verified that, for a molecule with one stereocenter, 21 = 2 stereoisomers (one pair of enantiomers) are possible • for a molecule with two stereocenters, a maximum of 22 = 4 stereoisomers (two pair of enantiomers) is possible • for a molecule with three stereocenters, a maximum of 23 = 8 stereoisomers (four pairs of enantiomers) is possible • and so forth

21. 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

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

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

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

25. 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

26. Polarimeter

27. 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

28. 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

29. 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 maximum number of stereoisomers possible is 2251! • only one of these stereoisomers is produced and used by any given organism • because enzymes are chiral substances, most either produce or react with only substances that match their stereochemical requirements

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

31. Chirality in Biomolecules • because interactions between molecules in living systems take place in a chiral environment, 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!

32. Chirality End Chapter 15