Chirality

1
Chirality

• 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

12
(No Transcript)
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 1-2-3 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