CHIRALITY: Handedness of
molecules
Greek “cheir” – hand; an object that is not
superposable on its minor image
Isomers – same (stereoisomers) or different
connectivity (constitutional isomers)
Stereoisomers are isomers that differ in spatial
arrangement of atoms or different orientation in space,
rather than order of atomic connectivity.
mirror-image stereoisomers, a non-superimposable set
of two molecules that are mirror image of one another.
The existence of these molecules are determined by
concept known as chirality.
Types of stereisomers
1. Geometric isomers- differ in the relative position(s) of substituents in a
rigid molecule.
Simple rotation about a C–C σ bond in an alkene, for example, cannot
occur because of the presence of the π bond.
The substituents are therefore rigidly locked into a particular spatial
arrangement.
Thus a carbon–carbon multiple bond, or in some cases a ring, prevents
one geometric isomer from being readily converted to the other.
The members of an isomeric pair are identified as either cis or trans
(achiral), and interconversion between the two forms requires breaking
and reforming one or more bonds.
Because their structural difference causes them to have different physical
and chemical properties, cis and trans isomers are actually two distinct
chemical compounds.
2. Optical isomers - molecules whose structures are mirror images but
cannot be uperimposed on one another in any orientation.
Optical isomers have identical physical properties, although
their chemical properties may differ in asymmetric environments.
Molecules that are nonsuperimposable mirror images of each other
are said to be chiral (pronounced “ky-ral,” from the Greek cheir,
meaning “hand”).
Examples of some familiar chiral objects are your hands, feet, and
ears.
Most chiral organic molecules have at least one carbon atom that is
bonded to four different groups, as occurs in the
bromochlorofluoromethane molecule
This carbon, often designated by an asterisk in structural drawings, is
called a chiral center or asymmetric carbon atom.
A molecule and its nonsuperimposable mirror image are called
enantiomers (from the Greek enantiou, meaning “opposite”).
A molecule and its superimposable non mirror image are called
diastereomers
Importance of enantiomers:
Majority of molecules in the biological world show this type isomerism
Almost one-half of all medications used to treat humans show this isomerism
Looking for planes of symmetry in a molecule is useful, but often difficult
in practice. In most cases, the easiest way to decide whether a molecule is
chiral or achiral is to look for one or more stereocenters - with a few rare
exceptions, the general rule is that molecules with at least one
stereocenter are chiral, and molecules with no stereocenters are
achiral. Carbon stereocenters are also referred to quite frequently
as chiral carbons.
When evaluating a molecule for chirality, it is important to recognize that
the question of whether or not the dashed/solid wedge drawing convention
is used is irrelevant. Chiral molecules are sometimes drawn without using
wedges (although obviously this means that stereochemical information is
being omitted). Conversely, wedges may be used on carbons that are not
stereocenters Just because you see dashed and solid wedges in a structure,
do not automatically assume that you are looking at a stereocenter.
Racemic mixture
An equimolar mixture of two enentiomers
From the term “racemic acid”(Latin: racemus, a cluster of grapes)
Racemic acid is the name originally given to an equimolar mixture
of the enantiomers of tartaric acid, a compound first isolated
from grapes.
Equal numbers of the dextrorotatory and the levorotatory
molecules, its specific rotation is 0°
Thalidomide:
In the 1960’s, a drug called thalidomide was widely prescribed in the Western
Europe to alleviate morning sickness in pregnant women.
Thalidomide had previously been used in other countries as an
antidepressant, and was believed to be safe and effective for both purposes.
The drug was not approved for use in the U.S.A. It was not long, however,
before doctors realized that something had gone horribly wrong: many babies
born to women who had taken thalidomide during pregnancy suffered from
severe birth defects
Researchers later realized that problem lay in the fact that thalidomide was
being provided as a mixture of two different isomeric forms.
One of the isomers is an effective medication, the other caused the side effects.
Both isomeric forms have the same molecular formula
and the same atom-to-atom connectivity, so they are not constitutional isomers.
Where they differ is in the arrangement in three-dimensional space about one
tetrahedral, sp3-hybridized carbon. These two forms of thalidomide
are stereoisomers.
Active enantiomer – 12 min effectivity
Racemic mixture – 30 min
The body converts the inactive form to active form
*Advil is a racemic mixture
Captopril- single enantiomer
-very effective for the treatment of high blood pressure
and congestive heart failure
Ways of presenting Enantiomers
How many stereocenters/chiral centers?
How many stereoisomers?
No. of stereoisomers = 2n , where n is the number of chiral
centers
Lactic acid
Cholesterol
