Stereochemistry & Chiral
Molecules
Isomerism
• Isomers are different compounds with the
same molecular formula
• 1) Constitutional isomers: their atoms are
connected in different order
• 2) Stereoisomers: their atoms are connected
in the same order, but have different
arrangement in space – enantiomers and
diastereomers (geometric isomers)
Isomers
Stereoisomers
Enantiomers
(nonsuperimposable
mirror images of
each other)
Constitutional
Isomers
Diastereomers (not
mirror images of
each other)
Stereoisomers
• 1) Enantiomers: If two molecules are
enantiomers of each other, one is
nonsuperimposable mirror image of the other
enantiomer
• 2) Diastereomers: If two molecules are
diastereomers, they are not mirror image of each
other, but they still have the same atomic
connectivity (such as cis-trans isomerism)
Examples of stereoisomers
diastereomer
same
enantiomer
Enantiomers and Chiral Molecules
• A chiral molecule is a molecule
that is not identical with its mirror
image
• A chiral molecule and its mirror
image are enantiomers
• Enantiomers are related to each
other in the same way left hand is
related to right hand (in this sense,
hand is chiral)
• If a molecule is not chiral, it is
called achiral (achiral molecule is
superimposable on its mirror
image)
https://www.mun.ca/biology/scarr/Amino_Acid_stereoisomers.html
How do we know if a molecule is chiral
and have enantiomers?
• One way is to look for a tetrahedral atom in the
molecule that has 4 different groups attached to it
• A chiral molecule does not have a plane of symmetry
• Interchanging any two groups of the tetrahedral atom
converts one enantiomer into the other
• This carbon atom is called stereocenter/asymmetric
carbon
• If the tetrahedral atom has two or more of the same
groups attached, it is not a stereocenter
• For a molecule to be chiral, it needs to have at least
one stereocenter (asymmetric carbon)
Biological Significance of Chirality
• Most of the molecules
that make up living
organisms are chiral –
mostly one form of the
chiral molecule is found
• Amino acids (except
one), building blocks of
proteins, are all chiral (Lamino acids – left
handed)
• Natural sugars are
almost all chiral (Dsugars, right handed)
Nomenclature of Enantiomers
• (R-S) system (also called Cahn-Ingold-Prelog
system) – one enantiomer is called R, the
other is called S
• (R) or (S) designation is decided based on
certain rules:
• In biology, D, L designation is used
L - (S)
D – (R)
Rules of (R-S) System
• 1) Each of the 4 groups attached to the stereocenter is given a priority,
based on the atomic number of the directly attached atom to the
stereocenter
• 2) If a priority can’t be assigned based on the first atom that is directly
attached to the stereocenter, we look at the next set of atoms in the
unassigned groups until we can make a decision
• 3) After priorities are determined for all 4 groups, we rotate the molecule
so that the group with lowest priority is directed away from us. For the 3
groups turned to us, we make a circle from highest priority to the lowest.
If the direction of the circle is clockwise, the molecule is (R) enantiomer, if
it is counterclockwise, it is (S) enantiomer.
• 4) If the groups contain double or triple bonds, we assign the priorities as
if both atoms were duplicated or triplicated
Properties of Enantiomers: Optical
Activity
• Enantiomers have identical chemical and physical
properties (melting point, boiling point, solubility etc.) –
unlike diastereomers
• There are two main differences between enantiomers:
• 1) Enantiomers show different properties only when they
interact with other chiral molecules (with other
enantiomers) For example, the solubility of enantiomers
will be different in a chiral solvent
• 2) Interaction with plane-polarized light – enantiomers
rotate the plane of plane-polarized light in opposite
directions (that is why they are called “optically active
compounds”)
Interaction with Plane-polarized Light
http://www.wiredchemist.com/chemistry/instructional/an-introduction-to-chemistry/structure/geometric-and-optical-isomers
Biological Significance of Chirality
• Chirality is important in interaction of chiral molecules
with chiral receptor sites or enzyme active sites - can
effect human beings differently:
Limonene: one enantiomer is responsible for the odor
of orange, the other enantiomer is for the odor of lemons
• Activity of drugs containing stereocenters might vary
between enantiomers; one enantiomer might cure, but
the other might be toxic
Racemic Mixture
• An equimolar mixture of two enantiomers is
called a racemic mixture (50% R, 50% S
enantiomer)
• A racemic mixture shows no rotation of planepolarized light
Molecules with Multiple Stereocenters
• Many of the biological organic
molecules contain more than
one stereocenter (cholesterol
contains 8 stereocenters)
• Rule for number of
stereoisomers:
- The total number of
stereoisomers can be maximum 2n
, where n is the number of
tetrahedral stereocenters
Diastereomers
• Two stereoisomers which are not enantiomers of
each other are diastereomers (have different physical
properties)
http://chemwiki.ucdavis.edu/Organic_Chemistry/Organic_Chemistry_With_a_Biological_Emphasis/Chapter_03%3A_Conformations_and_Stereochemistry
/Section_3.7%3A_Diastereomers
Meso compounds
• Molecules which have
a plane of symmetry
are achiral, even
though they contain
multiple stereocenters
• These compound are
called meso
compounds and they
are optically inactive
Fischer Projection Formulas
• Representation of chiral
molecules with twodimensional formulas
• Easier to write for
compounds with several
stereocenters – especially
used for sugars
• Vertical lines represent
behind or inside the plane of
the paper, horizontal lines
represent bonds that come
out of the plane of the
paper
Enantiomeric Excess
• If the amount of one enantiomer is greater
than the other enantiomer in a mixture, such
mixture is said to have enantiomeric excess
• 100 % (R) – enantiomeric excess of 100 %
• 70 % (R) + 30 % (S) – enantiomeric excess of
40 %
• 50 % (R) + 50 % (S) – racemic mixture
• Optical rotation will be in proportion to the
percentage of enantiomeric excess