Stereochemistry
Stereochemistry is the study of how molecules are affected by the way their atoms are
arranged in space.It is also known as 3D chemistry as the
word stereo means three dimensional.Using stereochemistry,
chemists can work out the relationships between different molecules that are
made up from the same atoms. They can also study the effect on the physical or biological properties these relationships give molecules.
When these relationships influence the reactivity of the molecules it is called dynamic stereochemistry.
In chemistry, some molecules have more than one isomer. This means that molecules can have different
forms, even though all the forms made up of the same atoms. There are two kinds
of isonomers. Constitutional isomers
have the same atoms, but they are joined differently. Stereoisomers have the
same atoms, they are joined the same way, but the atoms are arranged
differently in space. An important part of stereochemistry is the study of chiral molecules. These
molecules look almost identical, except that one molecule is the mirror image
of the other.
In most chemical bonds, the atoms of a molecule free to move
around without breaking the bonds. When a molecule has a double bond or a ring structure, the molecule can be
sorted into different isomers. These are molecules with the same chemical
structure but different forms.
The study of
stereochemical problems covers the entire range of organic, inorganic, biological, physical and supramolecular
chemistries.
HISTORY
Louis Pasteur was the first person to study stereochemistry.
He observed in 1849 that salts of tartaric acid
collected from wine-making equipment could rotate plane polarized light, but that salts from other sources did not.
This property was the only difference between the two types of salt. It is due
to optical
isomerism. In 1874, Jacobus Henricus
van 't Hoff and Joseph Le Bel
discovered the difference was caused by the way that the atoms
bonded to carbon in a tetrahedral (four faced) shape.
Uses of stereochemistry
Stereochemistry was important in solving the thalidomide disaster in the
1960s. Thalidomide is a drug
that was first produced in 1957 in Germany. Doctors used it to
treat morning sickness in pregnant
women. Later, the drug was shown to cause deformations in babies. One isomer of the drug was not
dangerous, but the other caused serious genetic damage to the embryos. In the human body,
thalidomide undergoes racemization: even if only one of the two stereoisomers
enters a human body, the body changes some of it to other one. The thalidomide
disaster caused governments to test drugs more carefully. Selected people take
new drugs in an experiment (clinical trial) first
before the drug is made available for public use. Thalidomide is now used as a therapy for leprosy. Women must use it
with contraceptives
to prevent pregnancy.
Describing a molecule's stereochemistry
Projection of a tetrahedral molecule
onto a planar surface.
Visualizing a Fischer projection.
When
an atom can have other atoms connect to it in more than one way, it is called a
stereocenter. For
example, if a carbon atom has four different groups attached to it, it becomes
a stereocenter.
Cahn-Ingold-Prelog priority rules are part of a system for
describing a molecule's stereochemistry. They rank the atoms around a
stereocenter in a standard way. This allows the relative position of these
atoms in the molecule to be described very clearly. A Fischer
projection is a simplified way to show the stereochemistry around a
stereocenter.
Types of stereoisomerism are:
·
Atropisomers are stereoisomers resulting from hindered
rotation about single bonds where the steric strain barrier to rotation is high enough to allow for
the isolation of the conformers. The word atropisomer is
derived from the Greek a, meaning not,
and tropos, meaning turn. The name was coined by Kuhn in 1933,
but atropisomerism was first detected in 6,6’-dinitro-2,2’-diphenic acid
by Christie in 1922.
Oki defined atropisomers as conformers that interconvert
with a half-life of more than 1000 seconds at a given temperature.
Atropisomers are an important class of compounds because they display axial chirality. They differ from other chiral compounds in that
they can be equilibrated thermally
whereas in the other forms of chirality isomerization is usually only possible
chemically.
The most important class of atropisomers are biaryls
such as diphenic acid, which is a derivative of biphenyl with a complete set of ortho substituents.
Others are dimers of naphthalene derivatives such as 1,1'-bi-2-naphthol. In a
similar way, aliphatic ring systems like cyclohexanes linked through a single bond may display
atropisomerism provided that bulky substituents are present.
Examples of naturally occurring atropisomers include vancomycin and knipholone, which is found in the roots of Kniphofia
foliosa of the family Asphodelaceae.
Separation of atropisomers is possibly by chiral resolution methods such as selective crystallization.
In an atropo-enantioselective or atropselective synthesis one
atropisomer is formed at the expense of the other. Atroposelective synthesis
may be carried out by use of chiral auxiliaries like a CBS catalyst in the total synthesis of knipholone or by approaches based on
thermodynamic equilibration when an isomerization reaction favors one
atropisomer over the other.
In organic chemistry BINAP is a ligand that is used in the
preparation of optically active stereoisomers.
Cis–trans isomerism
In organic chemistry, cis/trans
isomerism (also known as geometric isomerism, configuration
isomerism, or E/Z isomerism) is a form of stereoisomerism
describing the orientation of functional groups
within a molecule. In general, such isomers contain double bonds, which
cannot rotate, but they can also arise from ring structures, where in the
rotation of bonds is greatly restricted. Cis and trans isomers occur both
in organic molecules and in inorganic coordination complexes.
The terms cis and trans
are from Latin, in which cis means "on the same side" and trans
means "on the other side" or "across". The term
"geometric isomerism" is considered an obsolete synonym of "cis/trans
isomerism" by IUPAC. It is
sometimes used as a synonym for general stereoisomerism (e.g., optical isomerism
being called geometric isomerism); the correct term for non-optical
stereoisomerism is diastereomerism.
Cis-but-2-ene Trans-but-2-ene
Conformational isomerism
In chemistry, conformational isomerism is a form of stereoisomerism in which the isomers
can be interconverted exclusively by rotations about formally single bonds. Such
isomers are generally referred to as conformational isomers or conformers
and specifically as rotamers. when the rotation leading to different conformations
is restricted (hindered) rotation, in the sense that there exists a rotational
energy barrier that needs to be overcome to convert one conformer to another.
Conformational isomers are thus distinct from the other classes of
stereoisomers for which interconversion necessarily involves breaking and
reforming of chemical bonds. The rotational barrier, or barrier to rotation, is
the activation energy required
to interconvert rotamers.
Conformers of butane,
shown in Newman projection. The two
gauche as well as the anti form are staggered conformations
Diastereomer
Diastereomers (sometimes called diastereoisomers) are stereoisomers that are not enantiomers. Diastereomerism occurs when two or more
stereoisomers of a compound have different configurations at one or more (but
not all) of the equivalent (related) stereocenters and are not mirror images of each other.
When two diastereoisomers differ from each other at only one stereocenter they
are epimers. Each stereocenter gives rise to two different
configurations and thus increases the number of stereoisomers by a factor of
two.
Diastereomers
differ from enantiomers in that the latter are pairs of stereoisomers that
differ in all stereocenters and are therefore mirror images of one another. Enantiomers
of a compound with more than one stereocenter are also diastereomers of the
other stereoisomers of that compound that are not their mirror image.
Diastereomers have different physical properties (unlike enantiomers) and different chemical reactivity.
Cis-trans isomerism and conformational isomerism
are also forms of diastereomerism.
Diastereoselectivity is the preference for the formation of one or more than
one diastereomer over the other in an organic reaction.
Diastereomers
enantiomorphs
Organic
compounds that contain an asymmetric (chiral) Carbon usually have two
non-superimposable structures. These two structures are mirror images of each
other and are, thus, commonly called enantiomorphs (enantio =
opposite ; morph = form) Hence, optical isomerism (which occurs due
to these same mirror-image properties) is now commonly referred to as enantiomerism
Enantiopure
compounds refer to samples having, within the
limits of detection, molecules of only one chirality.
Enantiomers
have, when present in a symmetric environment, identical chemical and physical
properties except for their ability to rotate plane-polarized light (+/−) by equal amounts but in opposite
directions (although the polarized light can be considered an asymmetric
medium). A mixture of equal parts of an optically active isomer and its
enantiomer is termed racemic and has zero net rotation of
plane-polarized light because
the positive rotation of each (+) form is exactly counteracted by the negative
rotation of a (−) one.
Enantiomers
of each other often show different chemical reactions with other substances
that are also enantiomers. Since many molecules in the bodies of living beings
are enantiomers themselves, there is often a marked difference in the effects
of two enantiomers on living beings. In drugs, for example, often
only one of a drug's enantiomers is responsible for the desired physiologic
effects, while the other enantiomer is less active, inactive, or sometimes even
responsible for adverse effects (unwanted
side-effects).
Owing
to this discovery, drugs composed of only one enantiomer
("enantiopure") can be developed to enhance the pharmacological
efficacy and sometimes do away with some side effects. An example of this kind
of drug is eszopiclone (Lunesta), which is
enantiopure and therefore is given in doses that are exactly 1/2 of the older, racemic mixture called zopiclone. In the case of eszopiclone, the S enantiomer is
responsible for all the desired effects, though the other enantiomer seems to
be inactive; while an individual must take 2 mg of zopiclone to get the
same therapeutic benefit as they would receive from 1 mg of eszopiclone,
that appears to be the only difference between the two drugs.
(S)-(+)-lactic acid
(left) and (R)-(–)-lactic acid (right) are nonsuperposable mirror images
of each other
Chirality (chemistry)
A chiral
molecule /ˈkaɪərəl/ is a type of molecule that has a non-superposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom.[1][2]
The
term chiral in general is used to describe an object that is not
superposable on its mirror image. Achiral (not chiral) objects are
objects that are identical to their mirror image. Human hands
are perhaps the most universally recognized example of chirality: The left hand
is a non-superposable mirror image of the right hand; no matter how the two
hands are oriented, it is impossible for all the major features of both hands
to coincide. This difference in symmetry becomes obvious if someone attempts to
shake the right hand of a person using his left hand, or if a left-handed glove
is placed on a right hand. The term chirality is derived from the Greek
word for hand, χειρ (kheir). It is a mathematical approach to the concept of
"handedness".
In
chemistry, chirality usually refers to molecules. Two mirror images of a chiral
molecule are called enantiomers or optical isomers.
Pairs of enantiomers are often designated as "right-" and "left-handed".
Molecular
chirality is of interest because of its application to stereochemistry in inorganic chemistry, organic chemistry, physical chemistry, biochemistry, and supramolecular chemistry.
Two
enantiomers of a generic amino acid (S)-Alanine
(left) and (R)-alanine (right) in zwitterionic form at
neutral pH.
