Chapter 15: Chirality Chiral Stereoisomers Enantiomers R or S Enantiomers R or S Diastereomers D or L Diastereomers D or L

Chapter 15: Chirality chiral Objects that are nonsuperposable 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. stereocenter A carbon with four different groups bonded to it is called a stereocenter.

Chapter 15: Chirality Enantiomers: Enantiomers: Nonsuperposable mirror images. As an example of a molecule that exists as a pair of enantiomers, consider 2-butanol.

Chapter 15: Chirality To summarize; chiral 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. stereocenter We call a 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.

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.

Chapter 15: Chirality Step 1: Order groups by Priority. Higher Atomic number = Higher Priority

Chapter 15: Chirality Example: Example: Assign priorities to the groups in each set.

Chapter 15: Chirality Step 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

Chapter 15: Chirality Step 3: Follow the three groups projecting toward you in order from highest (1) to lowest (3) priority Steering Right = R configuration Steering Left = S configuration S R

Chapter 15: Chirality Example: Example: Assign an R or S configuration to each stereocenter.

Chapter 15: Chirality n 2 n For a molecule with n stereocenters, the maximum number of possible stereoisomers is 2 n. We have already verified that, for a molecule with one stereocenter, 2 1 = 2 stereoisomers (one pair of enantiomers) are possible. For a molecule with two stereocenters, a maximum of 2 2 = 4 stereoisomers (two pair of enantiomers) are possible. For a molecule with three stereocenters, a maximum of 2 3 = 8 stereoisomers (four pairs of enantiomers) are possible, and so forth. Diastereomers: Diastereomers: Stereoisomers that are not mirror images. (N>=2)

Chapter 15: Chirality Example: Example: Mark all stereocenters in each molecule and tell how many stereoisomers are possible for each.

Chapter 15: Chirality 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 (See next slide). Optically active: Optically active: Showing that a compound is capable rotating the plane of plane-polarized light.

Chapter 15: Chirality Figure 15.6 Schematic diagram of a polarimeter with its sample tube containing a solution of an optically active compound.

Chapter 15: Chirality Dextrorotatory: Dextrorotatory: Clockwise rotation of the plane of plane- polarized light. Indicated by (+ or D). Levorotatory: Levorotatory: Counterclockwise rotation of the plane of plane- polarized light. Indicated by (- or L). 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.

Chapter 15: Chirality 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.

Chapter 15: Chirality How an enzyme distinguishes between a molecule and its enantiomer. Figure 15.7 A schematic diagram of an enzyme surface that can interact with (R)-glyceraldehyde at three binding sites but with (S)-glyceraldehyde at only two of the three sites.

Chapter 15: Chirality Enzymes (protein biocatalysts) 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 ! 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.

Chapter 15: Chirality 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!