STEREOCHEMISTRY
Stereochemistry, a
subdiscipline of chemistry, involves the study of the relative spatial
arrangement of atoms
within molecules.
An important branch of stereochemistry is the study of chiral molecules.Stereochemistry is also known
as 3D chemistry because the prefix
"stereo-" means "three-dimensionality".The study of
stereochemical problems spans the entire range of organic,
inorganic, biological,
physical and supramolecular chemistries. Stereochemistry
includes methods for determining and describing these relationships; the effect
on the physical
or biological
properties these relationships impart upon the molecules in question, and the
manner in which these relationships influence the reactivity of the molecules
in question
Stereochemistry Tutorial
1. What are we talking about?
The bottom line of this
whole chapter is learning the difference between isomers. There are two
types of isomers, constitutional and stereoisomers. Constitutional
isomers are two compounds that have the same atoms present, but differ in their
connectivity.
ie:
ie:
These compounds contain
the same number of atoms, but the oxygen has been moved to form an ether
instead of an alcohol. Therefore, these compounds are constitutional
isomers.
Stereoisomers also have the same atoms present, however the
connectivity is the same. This means the same number of hydrogens will be
attached to each carbon and the same number of carbons will be attached to each
carbon. Picture this:
Now, these structures both
appear to be the same, but careful observation will reveal that the amine
groups attached are in the cis conformation on the left and the trans
conformation on the right. Therefore, the same atoms are present, but
just in a different spatial arrangement.
Not to beat this idea into your
head, but here is another example of a stereoisomer, but this time we will use
a hydrocarbon chain.
2. I understand that chiral compounds are mirror images of each other that are not superposable, but how do I tell they are superposable?
The easiest way to tell if the mirror image is
superimposable or not and superposable is to find the stereochemistry at the
stereocenter. This entails you to find the stereocenter first and then label
the groups attached to it in order of their priority. This means the atom with
the highest atomic number will be labeled A and the next highest B. The next
step is to rotate the molecule so the D group is facing away from you.
ie.
If the groups go from A to C clockwise, it is in the R
configuration. If the groups are arranged counterclockwise, it is in the S
configuration.
ie.
Practice a few
A has two stereocenters. The top stereocenter
is an R configuration and the bottom stereocenter is an S configuration.
For B the stereocenter is an S. C does not have to be
considered because there are two of the same groups attached, and is not
chiral.
If the two compounds you are
looking at are mirror images of each other, but the configuration at the
stereocenter differs, they are not superposable. Therefore they are
chiral compounds. If they are superposable, then they are
achiral.
3. How do I tell the difference between an Enantiomer and Diastereomer?
The easiest way to tell apart an enantiomer and a
diastereomer is to look at whether or not the compounds are mirror images of
each other. The best way to learn this is through practice. Here are a few
examples, see if you can determine whether or not the compounds are
enantiomers, the same, or diastereomers.
Hint:
first determine if the compounds are mirror images of each other, and then find
the individual stereochemistry around each chiral carbon. Remember the
hand rule or the clockwise/counterclockwise arrangement discussed in the
previous section
Stereochemistry of the Amino Acids
The a carbon of all of the amino acids, except
glycine, is a chiral center. Thus, the amino acids are optically active, and
each amino acid exists in two enantiomeric forms. These forms are designated as
"D-" and "L-" by comparison to the stereoisomers of
glutaraldhyde.
The L-forms of the amino acids are most common.
Some small peptides contain both D- and L-amino acids; these compounds are
synthesized non-ribosomally. Polypeptides which are synthesized using ribosomes
are made exclusively from L-amino acids.
The fact that proteins are made of only L-amino
acids, and are therfore chiral, is important in understanding their function.
Many proteins are exquisitely stereospecific. Some enzymes bind one stereoisomer
of a compound with a thousand times higher affinity than the related molecules.
Rotate these models to convince yourself that
these two molecules are, in fact, enantiomers (i.e non-superimposable mirror
images).
AMINO ACID STEREO CONFIGURATION
Optical activity (quantified by the rotation of the
plane of polarized light as it passes through a substance) was measured long
before the three dimensional structure of molecules could be determined by
methods such as X-ray Crystallography. The experimental assignment of optical
activity was then symbolized with the letter "d" or the "+"
sign (for dextrotatory, right handed or clockwise rotation of the plane of
polarized light when viewed toward the light source) and "l" or
"-" (for levorotatory, left hand or counterclockwise rotation).
Later the "D" and "L" symbols were associated with
absolute configuration based on the arbitrary, but as it turned out, correct
assignment of the absolute configuration of the dextrotatory and levorotatory
forms of glyceraldehyde. In this symbolism, absolute configuration is based on
chemical synthesis starting with glyceraldehyde (Fischer and Rosanoff) and
optical activity is specified using the "+" and "-"
notation.
A second absolute configuration notation using the
symbols R (from rectus, latin for right) and S (from sinister,
latin for left) was developed by Cahn, Ingold & Prelog. In this approach,
the substituents on an assymetric carbon (eg. a tetrahedral carbon with four
different substituents) are prioritized by decreasing atomic number.
Configuration is assigned by "looking" down the bond to the lowest
priority substituent and assigning R to the configuration where the remaining
subtituents are arranged clockwise in decreasing priority. S is then assigned
to the molecular form where the substituents are arranged counterclockwise.
Some other rules for assigning R/S configuration:
Group Priorities: SH > OH > NH2
> COOH > CHO > CH2OH > C6 H5 >
CH3 > H
Larger groups are ranked at their points of divergence, i.e. a CH2CH2SH
is greater than a CH2CH2OH
The absolute stereo configuration of the amino acids at the alpha carbon
is typically referred to using the D/L notation with reference to the absolute
configuration of Glyceraldehyde rather than the more modern R/S designation. In
R/S notation change of a single substituent can change assignment. However, all
of the amino acids used in proteins (except for glycine which is not optically
active) are of L configuration. However, in R/S notation cysteine is 2R,
whereas the others are 2S.
Both threonine and isoleucine have a second assymetric carbon center at carbon position 3 along their chains. The absolute configuration of the normal protein component, L-threonine, is 2S,3R. The mirror image compound (the enantiomer) is D-threonine (2R,3S). The diastereomer with 2S, 3S configuration is called L-allo-threonine (D-allo-threonine is then 2R, 3R). For isoleucine, the configuration of normal L-isoleucine is 2S, 3S.
NOTE: While L-threonine and L-isoleucine have different R/S configurations, the two molecules can be superimposed, i. e. the arrangement of the methyl group, the hydrogen atom and the backbone atoms are the same.
http://www.bmb.uga.edu/wampler/tutorial/aaconfig.html
Amino Acid Stereoisomers
Except for one AA, all
standard AAs have an asymmetric or chiral carbon. Thus, stereochemical
isomers exist for all but one of the standard amino acids.
- Structurally,
stereoisomers are defined as non-superimposable chemical isomers
that have identical covalent structures.
- There
are 2 classes of stereoisomers: enantiomers and diastereoisomers.
- Enantiomers
are mirror image chemical isomers.
Diastereoisomers
are non-mirror image chemical isomers
The convention
used to define the C carbon stereochemistry of amino acids is based on the
mirror image enantiomers of
glyceraldehyde, which is a three carbon structure having a
central chiral carbon. The two enantiomers of glyceraldehyde are
designated "D" and "L"
by reference to their unique optical activities. When a plane-polarized
light beam passes through a pure solution of D-glyceraldehyde the emergent beam will be rotated the light
plane to the right, and hence is the enantiomer is considered to be dextrorotatory
("dextra" is Latin for right) and is designated the "D"
enantiomer. However, if beam of plane polarized light passes
through a pure solution of L-glyceraldehyde, the emergent light beam will be rotated in the
opposite direction to the left, and hence the enantiomer is considered to be levorotatory
(laevus is Latin for left) and is designated the "L"
enantiomer. As expected, an equal molar mixture of D-
and L-glyceraldehyde will produce no rotation
for plane-polarized light passing through the solution because the left and
right rotational effects of the two pure enantiomers exactly cancel out. The
stereochemistry of most of the standard amino acids is defined by two possible
mirror image isomers or enantiomers. For example, consider the two enantiomers of
Ala. The standard amino acid itself, alanine, corresponds to
the L-stereoisomer, or L-Ala. It's mirror image enantiomer is the D-stereoisomer,
or D-Ala, which is rarely found in nature. The L-
and D-amino acid convention is defined by
matching their structures to the structures of L-glyceraldehyde and D-glyceraldehyde. First the asymmetric alpha-carbon
(C) of an amino acid is the aligned with the asymetric carbon 2 of
glyceraldehyde. Then, chemically similar groups in the structures are
oriented similarly. Namely, the amino acid carboxyl
group (COO-) is aligned parallel to the aldehyde
group (-CHO) of glyceraldehyde. The amino acid amino
group (NH3+) is aligned parallel to the hydroxyl
group (-OH) linked to the middle carbon of glyceraldehyde. Finally, the
variable amino acid R-group is aligned with the methanol group
(-CH2OH) of glyceraldehyde. In this configuration, the NH3+
group of every L-amino acid is
located on the left side and spacially above of the carbon just like
the -OH group linked to the second (asymmetric) carbon of L-glyceraldehyde.
This is one way of defining the stereochemistry of L-amino
acids but it is somewhat intuitive based on the similarities of the chemical
groups in the two types of molecules. Another system -- the R-S
convention -- is much more rigorous and is recommended for detailed of
stereochemical analysis .
Like the two
stereoisomers of glyceraldehyde, amino acid stereoisomers are also optically
active. Specially, pure solutions of all but one the standard amino acids will
rotate the plane of plane-polarized light to the left or right. However,
not all L-amino acids are levorotatory
and the actual direction of light rotation can very with amino acid depending
on its particular electronic and chemical structure in ways that are hard to
predict. In other words, some amino acids are levorotatory while
others are dextrorotatory for complicated structural reasons. However,
all standard amino acids are still considered to be L-amino
acids, independent of their optical active properties but consistent with their
overall structural homology to L-glyceraldehyde
in contrast to D-glyceraldehyde as discussed
above.
Two of the
standard amino acids, isoleucine and threonine,
have a second asymmetric carbon in addition to their carbons, namely their carbons.
The stereochemistry of these two amino acids is thus defined by 4
stereoisomers: i.e., two enantiomers as well as two
diastereoisomers (non-mirror-image stereoisomers) as illustrated in the
popup windows for Isoleucine
and Threonine
http://mcdb-webarchive.mcdb.ucsb.edu/sears/biochemistry/tw-amn/aas-stereo.htm
