1. Chirality - the Handedness of Molecules

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

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

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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

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

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

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

15. 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 is clockwise, the configuration is R; if reading them is counterclockwise, the configuration is S

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

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

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

19. 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

20. 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

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

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

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

24. 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

25. Polarimeter

26. 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

27. 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

28. 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

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

30. 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!

31. Chirality
End
Chapter 15