Chapter 14: Chirality - Handedness of Molecules

Isomers

• same molecular formula but different connectivity

• subdivided into: stereoisomers and constitutional isomers

Stereoisomers

• same connectivity

• subdivided into: achiral and chiral

Constitutional isomers

different connectivity

Achiral

• without stereocenters

• cis-trans isomers

Chiral

• with stereocenters

• subdivided into: enantiomers and diastereomers

Diastereomers

superposable mirror images

Enantiomers

• non superposable mirror images

• ex: 2-butanol

• always come in pairs

Rotate mirror image

one way to see that the mirror image of molecule is not superposable on the original molecule

Chiral

• objects that are non superposable on their mirror images

• greek: cheir - hand

• they show handedness

Presence of carbon bonded with 4 different groups

most common cause of enantiomerism in organic molecules

Stereocenter

carbon with 4 different groups bonded to it

Achiral

• An object and its mirror image are superposable, they are identical and there is no possibility of enantiomerism

• ex: 2-propanol (has no stereocenter)

180 degrees

degree of rotation to see that the mirror image of 2-butanol is not superposable on the original 

120 degrees

• Amount of degrees to rotate the mirror image to see its relationship with the original molecule

• it turns the mirror image back to how the original looked like

Inactive enantiomer of ibuprofen

active enantiomer of ibuprofen

R,S system

way to distinguish between enantiomers without having to draw them and point to one or the other

First step in assigning an R or S configuration to stereocenter

arrange the groups on the stereocenter in order of priority (higher atomic number, higher priority)

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

R configuration

If reading the (highest) groups 1-2-3 is clockwise

S configuration

if reading the (highest) groups 1-2-3 is counterclockwise

2^n

for molecules with n stereocenters, maximum number of possible stereoisomers

Molecule with 1 stereocenter

2^1 = 2 stereoisomers (one pair of enantiomers) are possible

Molecule with 2 stereocenters

maximum of 2^2 = 4 stereoisomers (two pairs of enantiomers) are possible 

Molecule with 3 stereocenters

maximum of 2³ = 8 stereoisomers (four pairs of enantiomers) are possible

Ordinary light

light waves oscillating in all planes perpendicular to its direction of propagation

Plane-polarized light

light waves oscillating 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 is capable of rotating the plane of plane-polarized light

Dextrorotatory

• Clockwise rotation of the plane of plane-polarized light

• Indicated by (+)

Levorotatory

• Counterclockwise rotation of the plane of plane-polarized light

• Indicated by (–)

Specific rotation

observed rotation of an optically active substance at a concentration of 1 g/mL in a sample tube 10 cm long

Molecules in living systems (plant and animals)

are chiral except for inorganic salts and a few low-molecular-weight organic substances

One stereoisomer

amount of stereoisomer found in nature

More than 1 stereoisomer in nature

possible but rarely exist together in the same biological system

(R)-glyceraldehyde

fits the 3 binding sites on enzyme surface

(S)-glyceraldehyde

fits only 2 of the 3 binding sites on enzyme surface

Enzymes (protein biocatalysts)

• all have many stereocenters

• ex: chymotrypsin

• because they are chiral substances, most either produce or react with only substances that match their stereochemical requirements

Chymotrypsin

• 251 stereoisomers

2^251!

• maximum number of possible stereoisomers

• only one of these stereoisomers is produced and used by any given organism

Chiral environment

• interactions between molecules in living systems take place here

  • this causes a molecule and its enantiomer or one of its diastereomers elicit different physiological responses

(S)-ibuprofen

• active as pain and fever reliever

• its R enantiomer is inactive

S enantiomer of naproxen

• active pain reliver 

• R enantiomer is a liver toxin