optical isomerism

OPTICAL ISOMERISM





SUBMITTED BY- Shweta Bhardwaj
COURSE - CHE-155
PROGRAMME- BSc (hons.) BIOTECH
PROGRAMME CODE- 178
ROLL NO.- R280A03
REGISTREATION NO.- 10801595
SUBMITTED TO- Dr. Ramesh Thakur




OPTICAL ISOMERISM
Optical isomerism is a form of stereoisomerism. This page explains what stereoisomers are and how you recognise the possibility of optical isomers in a molecule.
What is stereoisomerism?
What are isomers?
Isomers are molecules that have the same molecular formula, but have a different arrangement of the atoms in space. That excludes any different arrangements which are simply due to the molecule rotating as a whole, or rotating about particular bonds.
Where the atoms making up the various isomers are joined up in a different order, this is known as structural isomerism. Structural isomerism is not a form of stereoisomerism, and is dealt with on a separate page.

What are stereoisomers?
In stereoisomerism, the atoms making up the isomers are joined up in the same order, but still manage to have a different spatial arrangement. Optical isomerism is one form of stereoisomerism.
Optical isomerism
Why optical isomers?
Optical isomers are named like this because of their effect on plane polarised light.

Simple substances which show optical isomerism exist as two isomers known as enantiomers.
• A solution of one enantiomer rotates the plane of polarisation in a clockwise direction. This enantiomer is known as the (+) form.
For example, one of the optical isomers (enantiomers) of the amino acid alanine is known as (+)alanine.
• A solution of the other enantiomer rotates the plane of polarisation in an anti-clockwise direction. This enantiomer is known as the (-) form. So the other enantiomer of alanine is known as or (-)alanine.
• If the solutions are equally concentrated the amount of rotation caused by the two isomers is exactly the same - but in opposite directions.
• When optically active substances are made in the lab, they often occur as a 50/50 mixture of the two enantiomers. This is known as a racemic mixture or racemate. It has no effect on plane polarised light.

How optical isomers arise
The examples of organic optical isomers required at A' level all contain a carbon atom joined to four different groups. These two models each have the same groups joined to the central carbon atom, but still manage to be different:

Obviously as they are drawn, the orange and blue groups aren't aligned the same way. Could you get them to align by rotating one of the molecules? The next diagram shows what happens if you rotate molecule B.

They still aren't the same - and there is no way that you can rotate them so that they look exactly the same. These are isomers of each other.
They are described as being non-superimposable in the sense that (if you imagine molecule B being turned into a ghostly version of itself) you couldn't slide one molecule exactly over the other one. Something would always be pointing in the wrong direction.

What happens if two of the groups attached to the central carbon atom are the same? The next diagram shows this possibility.

The two models are aligned exactly as before, but the orange group has been replaced by another pink one.
Rotating molecule B this time shows that it is exactly the same as molecule A. You only get optical isomers if all four groups attached to the central carbon are different.

Chiral and achiral molecules
The essential difference between the two examples we've looked at lies in the symmetry of the molecules.
If there are two groups the same attached to the central carbon atom, the molecule has a plane of symmetry. If you imagine slicing through the molecule, the left-hand side is an exact reflection of the right-hand side.
Where there are four groups attached, there is no symmetry anywhere in the molecule.

A molecule which has no plane of symmetry is described as chiral. The carbon atom with the four different groups attached which causes this lack of symmetry is described as a chiral centre or as an asymmetric carbon atom.
The molecule on the left above (with a plane of symmetry) is described as achiral.
Only chiral molecules have optical isomers.
The relationship between the enantiomers
One of the enantiomers is simply a non-superimposable mirror image of the other one.
In other words, if one isomer looked in a mirror, what it would see is the other one. The two isomers (the original one and its mirror image) have a different spatial arrangement, and so can't be superimposed on each other.

If an achiral molecule (one with a plane of symmetry) looked in a mirror, you would always find that by rotating the image in space, you could make the two look identical. It would be possible to superimpose the original molecule and its mirror image.
Some real examples of optical isomers
Butan-2-ol
The asymmetric carbon atom in a compound (the one with four different groups attached) is often shown by a star.

It's extremely important to draw the isomers correctly. Draw one of them using standard bond notation to show the 3-dimensional arrangement around the asymmetric carbon atom. Then draw the mirror to show the examiner that you know what you are doing, and then the mirror image.



Notice that you don't literally draw the mirror images of all the letters and numbers! It is, however, quite useful to reverse large groups - look, for example, at the ethyl group at the top of the diagram.
It doesn't matter in the least in what order you draw the four groups around the central carbon. As long as your mirror image is drawn accurately, you will automatically have drawn the two isomers.
So which of these two isomers is (+)butan-2-ol and which is (-)butan-2-ol? There is no simple way of telling that. For A'level purposes, you can just ignore that problem - all you need to be able to do is to draw the two isomers correctly.
2-hydroxypropanoic acid (lactic acid)
Once again the chiral centre is shown by a star.

The two enantiomers are:

It is important this time to draw the COOH group backwards in the mirror image. If you don't there is a good chance of you joining it on to the central carbon wrongly.

If you draw it like this in an exam, you won't get the mark for that isomer even if you have drawn everything else perfectly.
2-aminopropanoic acid (alanine)
This is typical of naturally-occurring amino acids. Structurally, it is just like the last example, except that the -OH group is replaced by -NH2

The two enantiomers are:

Only one of these isomers occurs naturally: the (+) form. You can't tell just by looking at the structures which this is.
It has, however, been possible to work out which of these structures is which. Naturally occurring alanine is the right-hand structure, and the way the groups are arranged around the central carbon atom is known as an L- configuration. Notice the use of the capital L. The other configuration is known as D-.
So you may well find alanine described as L-(+)alanine.
That means that it has this particular structure and rotates the plane of polarisation clockwise.
Even if you know that a different compound has an arrangement of groups similar to alanine, you still can't say which way it will rotate the plane of polarisation.
The other amino acids, for example, have the same arrangement of groups as alanine does (all that changes is the CH3 group), but some are (+) forms and others are (-) forms.
It's quite common for natural systems to only work with one of the enantiomers of an optically active substance. It isn't too difficult to see why that might be. Because the molecules have different spatial arrangements of their various groups, only one of them is likely to fit properly into the active sites on the enzymes they work with.
In the lab, it is quite common to produce equal amounts of both forms of a compound when it is synthesised. This happens just by chance, and you tend to get racemic mixtures.
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Note: For a detailed discussion of this, you could have a look at the page on the addition of HCN to aldehydes
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Chirality




Two enantiomers of a generic amino acid


The two optical isomers of alanine.


The two enantiomers of bromochlorofluoromethane
The term chiral (pronounced /ˈkaɪrəl/) is used to describe an object that is non-superposable on its 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 (/cheir/).
When used in the context of chemistry, chirality usually refers to molecules. Two mirror images of a molecule that cannot be superposed onto each other are referred to as enantiomers or optical isomers. Because the difference between right and left hands is universally known and easy to observe, many pairs of enantiomers are designated as "right-" and "left-handed." A mixture of equal amounts of the two enantiomers is said to be a racemic mixture. Molecular chirality is of interest because of its application to stereochemistry in inorganic chemistry, organic chemistry, physical chemistry, biochemistry, and supramolecular chemistry.
The symmetry of a molecule (or any other object) determines whether it is chiral. A molecule is achiral (not chiral) if and only if it has an axis of improper rotation; that is, an n-fold rotation (rotation by 360°/n) followed by a reflection in the plane perpendicular to this axis that maps the molecule onto itself. (See chirality (mathematics).) A simplified rule applies to tetrahedrally-bonded carbon, as shown in the illustration: if all four substituents are different, the molecule is chiral. A chiral molecule is not necessarily asymmetric, that is, devoid of any symmetry elements, as it can have, for example, rotational symmetry.

History
The term optical activity is derived from the interaction of chiral materials with polarized light. A solution of the (−)-form of an optical isomer rotates the plane of polarization of a beam of plane polarized light in a counterclockwise direction, vice-versa for the (+) optical isomer. The property was first observed by Jean-Baptiste Biot in 1815 [1], and gained considerable importance in the sugar industry, analytical chemistry, and pharmaceuticals. Louis Pasteur deduced in 1848 that this phenomenon has a molecular basis[2]. Artificial composite materials displaying the analog of optical activity but in the microwave region were introduced by J.C. Bose in 1898 [3], and gained considerable attention from the mid-1980s [4]. The term chirality itself was coined by Lord Kelvin in 1873.[1]
The word “racemic” is derived from the Latin word for grape; the term having its origins in the work of Louis Pasteur who isolated racemic tartaric acid from wine.
Naming conventions
By configuration: R- and S-
For chemists, the R / S system is the most important nomenclature system for denoting enantiomers, which does not involve a reference molecule such as glyceraldehyde. It labels each chiral center R or S according to a system by which its substituents are each assigned a priority, according to the Cahn Ingold Prelog priority rules(CIP), based on atomic number. If the center is oriented so that the lowest-priority of the four is pointed away from a viewer, the viewer will then see two possibilities: If the priority of the remaining three substituents decreases in clockwise direction, it is labeled R (for Rectus), if it decreases in counterclockwise direction, it is S (for Sinister).
This system labels each chiral center in a molecule (and also has an extension to chiral molecules not involving chiral centers). Thus, it has greater generality than the D/L system, and can label, for example, an (R,R) isomer versus an (R,S) — diastereomers.
The R / S system has no fixed relation to the (+)/(−) system. An R isomer can be either dextrorotatory or levorotatory, depending on its exact substituents.
The R / S system also has no fixed relation to the D/L system. For example, the side-chain one of serine contains a hydroxyl group, -OH. If a thiol group, -SH, were swapped in for it, the D/L labeling would, by its definition, not be affected by the substitution. But this substitution would invert the molecule's R / S labeling, because the CIP priority of CH2OH is lower than that for CO2H but the CIP priority of CH2SH is higher than that for CO2H.
For this reason, the D/L system remains in common use in certain areas of biochemistry, such as amino acid and carbohydrate chemistry, because it is convenient to have the same chiral label for all of the commonly occurring structures of a given type of structure in higher organisms. In the D/L system, they are all L; in the R / S system, they are mostly S but there are some common exceptions.
By optical activity: (+)- and (−)-
An enantiomer can be named by the direction in which it rotates the plane of polarized light. If it rotates the light clockwise (as seen by a viewer towards whom the light is traveling), that enantiomer is labeled (+). Its mirror-image is labeled (−). The (+) and (−) isomers have also been termed d- and l-, respectively (for dextrorotatory and levorotatory). This labeling is easy to confuse with D- and L-.
By configuration: D- and L-
An optical isomer can be named by the spatial configuration of its atoms. The D/L system does this by relating the molecule to glyceraldehyde. Glyceraldehyde is chiral itself, and its two isomers are labeled D and L. Certain chemical manipulations can be performed on glyceraldehyde without affecting its configuration, and its historical use for this purpose (possibly combined with its convenience as one of the smallest commonly used chiral molecules) has resulted in its use for nomenclature. In this system, compounds are named by analogy to glyceraldehyde, which, in general, produces unambiguous designations, but is easiest to see in the small biomolecules similar to glyceraldehyde. One example is the amino acid alanine, which has two optical isomers, and they are labeled according to which isomer of glyceraldehyde they come from. On the other hand, glycine, the amino acid derived from glyceraldehyde, has no optical activity, as it is not chiral (achiral). Alanine, however, is chiral.
The D/L labeling is unrelated to (+)/(−); it does not indicate which enantiomer is dextrorotatory and which is levorotatory. Rather, it says that the compound's stereochemistry is related to that of the dextrorotatory or levorotatory enantiomer of glyceraldehyde—the dextrorotatory isomer of glyceraldehyde is, in fact, the D isomer. Nine of the nineteen L-amino acids commonly found in proteins are dextrorotatory (at a wavelength of 589 nm), and D-fructose is also referred to as levulose because it is levorotatory.
A rule of thumb for determining the D/L isomeric form of an amino acid is the "CORN" rule. The groups:
COOH, R, NH2 and H (where R is a variant carbon chain)
are arranged around the chiral center carbon atom. Sighting with the hydrogen atom away from the viewer, if these groups are arranged clockwise around the carbon atom, then it is the D-form. If counter-clockwise, it is the L-form.
Nomenclature
• Any non-racemic chiral substance is called scalemic [2]
• A chiral substance is enantiopure or homochiral when only one of two possible enantiomers is present.
• A chiral substance is enantioenriched or heterochiral when an excess of one enantiomer is present but not to the exclusion of the other.
• Enantiomeric excess or ee is a measure for how much of one enantiomer is present compared to the other. For example, in a sample with 40% ee in R, the remaining 60% is racemic with 30% of R and 30% of S, so that the total amount of R is 70%.
Types
In general, chiral molecules have point chirality, centering around a single atom, usually carbon, which has four different substituents. The two enantiomers of such compounds are said to have different absolute configurations at this center. This center is thus stereogenic (i.e., a grouping within a molecular entity that may be considered a focus of stereoisomerism), and is exemplified by the α-carbon of amino acids. A molecule can have multiple chiral centers without being chiral overall if there is a symmetry element (a mirror plane or inversion center), which relates the two (or more) chiral centers. Such a molecule is called a meso compound. It is also possible for a molecule to be chiral without having actual point chirality. Common examples include 1,1'-bi-2-naphthol (BINOL) and 1,3-dichloro-allene, which have axial chirality, and (E)-cyclooctene, which has planar chirality.
It is important to keep in mind that molecules that are dissolved in solution or are in the gas phase usually have considerable flexibility, and, thus, may adopt a variety of different conformations. These various conformations are themselves almost always chiral. However, when assessing chirality, one must use a structural picture of the molecule that corresponds to just one chemical conformation - the most symmetric conformation possible.
When the optical rotation for an enantiomer is too low for practical measurement it is said to exhibit cryptochirality.
Even isotopic differences must be considered when examining chirality. Replacing one of the two 1H atoms at the CH2 position of benzyl alcohol with a deuterium (²H) makes that carbon a stereocenter. The resulting benzyl-α-d alcohol exists as two distinct enantiomers, which can be assigned by the usual stereochemical naming conventions. The S enantiomer has [α]D = +0.715°.[5]
Properties of enantiomers
Enantiomers are identical with respect to ordinary chemical reactions and properties (i.e., will have identical Rfs by TLC, identical NMR spectra, identical IR spectra), but differences arise when they are in the presence of other chiral molecules or objects. Different enantiomers of chiral compounds often taste and smell differently and have different effects as drugs - see below.
One chiral 'object' that interacts differently with the two enantiomers of a chiral compound is circularly polarised light: An enantiomer will absorb left- and right-circularly polarised light to differing degrees. This is the basis of circular dichroism (CD) spectroscopy. Usually the difference in absorptivity is relatively small (parts per thousand). CD spectroscopy is a powerful analytical technique for investigating the secondary structure of proteins and for determining the absolute configurations of chiral compounds, in particular, transition metal complexes. CD spectroscopy is replacing polarimetry as a method for characterising chiral compounds, although the latter is still popular with sugar chemists.
In biology
Many biologically active molecules are chiral, including the naturally occurring amino acids (the building blocks of proteins), and sugars. In biological systems, most of these compounds are of the same chirality: most amino acids are L and sugars are D. Typical naturally occurring proteins, made of L amino acids, are known as left-handed proteins, whereas D amino acids produce right-handed proteins.
The origin of this homochirality in biology is the subject of much debate.[6] Most scientists believe that Earth life's “choice” of chirality was purely random, and that if carbon-based life forms exist elsewhere in the universe, their chemistry could theoretically have opposite chirality.
Enzymes, which are chiral, often distinguish between the two enantiomers of a chiral substrate. Imagine an enzyme as having a glove-like cavity that binds a substrate. If this glove is right-handed, then one enantiomer will fit inside and be bound, whereas the other enantiomer will have a poor fit and is unlikely to bind.
D-form amino acids tend to taste sweet, whereas L-forms are usually tasteless. Spearmint leaves and caraway seeds, respectively, contain L-carvone and D-carvone - enantiomers of carvone. These smell different to most people because our olfactory receptors also contain chiral molecules that behave differently in the presence of different enantiomers.
Chirality is important in context of ordered phases as well, for example the addition of a small amount of an optically active molecule to a nematic phase (a phase that has long range orientational order of molecules) transforms that phase to a chiral nematic phase (or cholesteric phase). Chirality in context of such phases in polymeric fluids has also been studied in this context (Srinivasarao, 1999).
In drugs
Many chiral drugs must be made with high enantiomeric purity due to potential side-effects of the other enantiomer. (The other enantiomer may also merely be inactive.)
• Thalidomide: Thalidomide is racemic. One enantiomer is effective against morning sickness, whereas the other is teratogenic. In this case, administering just one of the enantiomers to a pregnant patient does not help, as the two enantiomers are readily interconverted in vivo. Thus, if a person is given either enantiomer, both the D and L isomers will eventually be present in the patient's serum.
• Ethambutol: Whereas one enantiomer is used to treat tuberculosis, the other causes blindness.
• Naproxen: One enantiomer is used to treat arthritis pain, but the other causes liver poisoning with no analgesic effect.
• Steroid receptor sites also show stereoisomer specificity.
• Penicillin's activity is stereodependent. The antibiotic must mimic the D-alanine chains that occur in the cell walls of bacteria in order to react with and subsequently inhibit bacterial transpeptidase enzyme.
• Only L-propranolol is a powerful adrenoceptor antagonist, whereas D-propranolol is not. However, both have local anesthetic effect.
• The L-isomer of Methorphan, levomethorphan is a potent opioid analgesic, while the D-isomer, dextromethorphan is a dissociative cough suppressant.
• S(-) isomer of carvedilol, a drug that interacts with adrenoceptors, is 100 times more potent as beta receptor blocker than R(+) isomer. However, both the isomers are approximately equipotent as alpha receptor blockers.
• The D-isomers of amphetamine and methamphetamine are strong CNS stimulants, while the L-isomers of both drugs lack appreciable CNS(central nervous system) stimulant effects, but instead stimulate the peripheral nervous system. For this reason, the Levo-isomer of methamphetamine is available as an OTC nasal inhaler in some countries, while the Dextro-isomer is banned from medical use in all but a few countries in the world, and highly regulated in those countries who do allow it to be used medically.
In inorganic chemistry
Many coordination compounds are chiral; for example, the well-known [Ru(2,2'-bipyridine)3]2+ complex in which the three bipyridine ligands adopt a chiral propeller-like arrangement [7]. In this case, the Ru atom may be regarded as a stereogenic center, with the complex having point chirality. The two enantiomers of complexes such as [Ru(2,2'-bipyridine)3]2+ may be designated as Λ (left-handed twist of the propeller described by the ligands) and Δ (right-handed twist). Hexol is a chiral cobalt complex that was first investigated by Alfred Werner. Resolved hexol is significant as being the first compound devoid of carbon to display optical activity.
Chirality of amines

Tertiary amines (see image) are chiral in a way similar to carbon compounds: The nitrogen atom bears four distinct substituents counting the lone pair. However, the energy barrier for the inversion of the stereocenter is, in general, about 30 kJ/mol, which means that the two stereoisomers are rapidly interconverted at room temperature. As a result, amines such as NHRR' cannot be resolved optically and NRR'R" can only be resolved when the R, R', and R" groups are constrained in cyclic structures.
Theory of origin
A paper published in February 29, 2008 by researchers led by Sandra Pizzarello, from Arizona State University, reveals that the Murchison meteorite contains sizable molecular asymmetry of up to 14%, "giving support to the idea that biomolecular traits such as chiral asymmetry could have been seeded in abiotic chemistry ahead of life."[8]
"Thanks to the pristine nature of this meteorite, we were able to demonstrate that other extraterrestrial amino acids carry the left-handed excesses in meteorites and, above all, that these excesses appear to signify that their precursor molecules, the aldehydes, also carried such excesses," Pizzarello said. "In other words, a molecular trait that defines life seems to have broader distribution as well as a long cosmic lineage."[3]
Other theories of the origin of chirality on Earth have also been proposed, such as the weak nuclear force.[4]
Chemical chirality in Fiction
Although little was known about chemical chirality in the time of Lewis Carroll, his work Through the Looking-glass contains a prescient reference to the differing biological activities of enantiomeric drugs: "Perhaps Looking-glass milk isn't good to drink," Alice said to her cat.
In James Blish's Star Trek novella Spock Must Die! the tachyon 'mirrored' Mr Spock is later discovered to have stolen chemical reagents from the medical bay and to have been using them to convert certain amino acids to opposite-chirality isomers, since the mirrored Mr Spock's metabolism is reversed, and, hence, must process the opposite polarity of these isomers.
In Larry Niven's Destiny's Road, the title planet's indigenous life is based upon right-handed proteins. When human colonists arrive from Earth via a generation ship, extreme measures are taken to permit the colony's survival. A peninsula is sterilized with a lander's fusion drive, creating the titular "road" out of fused bedrock. The area is then reseeded with Earth life to provide the colonists with food. Though the soil lacks potassium due to other factors, necessitating supplements that produce a hydraulic empire common to Niven's fiction, the colony otherwise prospers. Native viruses and bacteria cannot infect colonists, resulting in longer lifespans. Sealife quickly recovers, and is consumed by the colonists as a "diet" food, as their digestive systems cannot metabolize it into fat.
In the Trauma Center series of games, doctors test for a "chiral reaction" in order to determine whether or not a patient is infected with "Gangliated Utrophin Immuno Latency Toxin," a fictional, parasitic pathogen more commonly referred to as G.U.I.L.T. A positive reaction means the patient is infected, while a negative reaction means the patient has either been cured or is not infected.
translation of French original, published by Alembic Club Reprints (Vol. 14, pp. 1-46) in 1905, facsimile reproduction by SPIE in a 1990 book". Notes
Structure and Optical Isomerism
A very important feature of the structure of amino acids (and other kinds of compounds as well, for that matter) is called optical isomerism. It applies to all amino acids except glycine.
Look at the number-two carbon atom. You should notice that in one direction it is bonded to an amino group. In another direction, it is bonded to a carboxylic group. It is also bonded to a hydrogen atom and an alkyl group or some other kind of group. Except in the case of glycine where -R is a -H, that number two carbon atom is bonded to four different groups. A carbon atom which is attached to four different groups is called an asymmetric carbon atom or sometimes a chiral carbon atom. The importance of this depends on some structural properties that we will investigate in this section.



If you are in the lab you get a model kit and follow along with the diagrams shown here. Get a carbon atom and attach to it four different groups. For convenience just use different colored units, rather than actually building an amino group and a carboxylic acid group and an isopropyl group or something like that. Then make the other models as they are shown bleow. If you are not in the lab now, you should work with the models to do this exercise when you are in the lab.
Here is a model of a carbon atom with four different groups attached.


Here is another model constructed to be the mirror image of the first model. To do this, construct a model that would appear just as the first model that you made would look like if you were looking at it in a mirror.


Here you can see why these are called mirror images of one another.


We can demonstrate that these two structures are not identical to one another by trying to superimpose one structure on another and get all of the same colored units to be in the identical places. You can see that is not possible.


The two structures are different. They are isomers of one another. It so happens that they are called optical isomers of one another because they have optical properties that are different from one another. We will discuss that particular property a little bit more when we discuss carbohydrates in a later lesson.



When asymmetric carbon atoms are present in a molecular compound, there are two ways in which the groups attached to that carbon can be arranged in the three dimensions, as we have just shown with the two models above. It is generally true, if not universally true, that only one of these optical isomers is biologically active. In other words, when these compounds are made by a plant or animal, only one of the two forms is made. When it comes time for these molecules to interact with an enzyme, only one of these molecules would react. The other would not. Both shape and orientation in biological compounds are extremely important.
Chemically, optical isomers behave the same. Biologically, they do not. One will react properly, but the other will not. Optically, there is also that difference which will be pointed out when we deal with carbohydrates in a later lesson.
We can use these models to illustrate why you need to have four different groups bonded to the central atom. One group (the black group) has been removed from the model on the left and replaced it with a duplicate of one of the other three groups (the white group). We now have a model with the central atom bonded to four groups, but they are not all different. The same has been done to the mirror image (unfortunately, you cannot see that).


By turning the second model in the right way you can see that it is identical to the first one.


Consequently, this central atom is not an asymmetric carbon atom, the molecule is not an optically active molecule, and these are identicalcompounds and not optical isomers.



References
1. ^ Pedro Cintas. "Tracing the Origins and Evolution of Chirality and Handedness in Chemical Language". Angewandte Chemie International Edition 46 (22): 4016-4024. doi:10.1002/anie.200603714.
2. ^ Infelicitous stereochemical nomenclatures for stereochemical nomenclature
3. ^ Arizona State University (2008, February 29). Key To Life Before Its Origin On Earth May Have Been Discovered. ScienceDaily. Retrieved June 16, 2008, from http://www.sciencedaily.com/releases/2008/02/080228174823.htm
4. ^ Castelvecchi, Davide. (2007). Alien Pizza, Anyone?, Science News vol. 172, pp. 107-109. (references