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:

 

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.

Notice that the chain on the left is in the cis conformation at the double bond and the chain on the right is trans.  This makes them stereoisomers

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.

 

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).

http://webhost.bridgew.edu/fgorga/proteins/stereochem.htm

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

stereochemistry VIDEO

http://www.youtube.com/watch?v=iq7GnIdEb9s&noredirect=1

about Stereochemistry 7 - Difficult assignment problem: Absolute configuration

http://studystove.com/stereochemistry-example