What makes an object chiral

For chiral molecules indicate any chiral carbons. Structures F and G are achiral. The former has a plane of symmetry passing through the chlorine atom and bisecting the opposite carbon-carbon bond.

The similar structure of compound E does not have such a symmetry plane, and the carbon bonded to the chlorine is a chiral center the two ring segments connecting this carbon are not identical.

Structure G is essentially flat. All the carbons except that of the methyl group are sp 2 hybridized, and therefore trigonal-planar in configuration. 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. 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 the 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, sp 3 -hybridized carbon.

These two forms of thalidomide are stereoisomers. If you make models of the two stereoisomers of thalidomide, you will see that they too are mirror images, and cannot be superimposed. As a historical note, thalidomide was never approved for use in the United States.

This was thanks in large part to the efforts of Dr. Frances Kelsey, a Food and Drug officer who, at peril to her career, blocked its approval due to her concerns about the lack of adequate safety studies, particularly with regard to the drug's ability to enter the bloodstream of a developing fetus.

Unfortunately, though, at that time clinical trials for new drugs involved widespread and unregulated distribution to doctors and their patients across the country, so families in the U. Very recently a close derivative of thalidomide has become legal to prescribe again in the United States, with strict safety measures enforced, for the treatment of a form of blood cancer called multiple myeloma.

In Brazil, thalidomide is used in the treatment of leprosy - but despite safety measures, children are still being born with thalidomide-related defects. Label the molecules below as chiral or achiral, and locate all stereocenters. Here are some more examples of chiral molecules that exist as pairs of enantiomers. In each of these examples, there is a single stereocenter, indicated with an arrow.

Many molecules have more than one stereocenter, but we will get to that that a little later! Here are some examples of molecules that are achiral not chiral. Notice that none of these molecules has a stereocenter. Chirality is tied conceptually to the idea of asymmetry, and any molecule that has a plane of symmetry cannot be chiral.

When looking for a plane of symmetry, however, we must consider all possible conformations that a molecule could adopt. Even a very simple molecule like ethane, for example, is asymmetric in many of its countless potential conformations — but it has obvious symmetry in both the eclipsed and staggered conformations, and for this reason it is achiral. 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 see section 3.

Carbon stereocenters are also referred to quite frequently as chiral carbons. 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 — look, for example, at the drawings of glycine and citrate in the figure above.

Just because you see dashed and solid wedges in a structure, do not automatically assume that you are looking at a stereocenter. Other elements in addition to carbon can be stereocenters.

The phosphorus center of phosphate ion and organic phosphate esters, for example, is tetrahedral, and thus is potentially a stereocenter. The same thing applies to some molecules. A chiral molecule has a mirror image that cannot line up with it perfectly- the mirror images are non superimposable. The mirror images are called enantiomers. But why are chiral molecules so interesting?

A chiral molecule and its enantiomer have the same chemical and physical properties boiling point, melting point,polarity, density etc…. It turns out that many of our biological molecules such as our DNA, amino acids and sugars, are chiral molecules. It is pretty interesting that our hands seem to serve the same purpose but most people are only able to use one of their hands to write.

Similarily this is true with chiral biological molecules and interactions. Just like your left hand will not fit properly in your right glove, one of the enantiomers of a molecule may not work the same way in your body. This must mean that enantiomers have properties that make them unique to their mirror images.

One of these properties is that they cannot have a plan e of symmetry or an internal mirror plane. So, a chiral molecule cannot be divided in two mirror image halves. Another property of chiral molecules is optical activity. A very important point to keep in mind about any pair of enantiomers is that they will have identical chemical and physical properties, except for the signs of their optical rotations, with one important proviso: All of the properties to be compared must be determined using achiral reagents in a solvent made up of achiral molecules or, in short, in an achiral environment.

As mentioned before, chiral molecules are very similar to each other since they have the same components to them. The only thing that obviously differs is their arrangement in space. As a result of this similarity, it is very hard to distinguish chiral molecules from each other when we try to compare their properties such as boiling points, melting points and densities.

A beam of plane-polarized light, when passed through a sample of a chiral compound, interacts with the compound in such a way that the angle of oscillation will rotate.

This property is called optical activity. The magnitude of the observed optical activity is dependent on temperature, the wavelength of light used, solvent, concentration of the chiral sample, and the path length of the sample tube path length is the length that the plane-polarized light travels through the chiral sample. Every chiral molecule has a characteristic specific rotation, which is recorded in the chemical literature as a physical property just like melting point or density. Different enantiomers of a compound will always rotate plane-polarized light with an equal but opposite magnitude.

For example, the S enantiomer of ibuprofen is dextrorotatory, but the S enantiomer of glyceraldehyde is levorotatory. A mixture of two enantiomers a racemic mixture will have no observable optical activity, because the two optical activities cancel each other out. Methods used in assigning the true configurations to enantiomers will be discussed later. Schematic representation of the rotation of the plane of polarization of polarized light by an optically active compound.

Plane-polarized light is different from ordinary light in that its electrical component vibrates in a plane rather than in all directions. Le Bel. Two enantiomers of a chiral molecule, being non-superimposable, are different compounds. How do they differ?

Each pair of enantiomers has identical physical and chemical properties towards achiral properties, such as melting point, boiling point, refractive index, infrared spectrum, the solubility in the same solvent, or the same reaction rate with achiral reagents. The differences emerge when they interacts with chemical and physical phenomena that have chiral properties. The optical activity of materials such as quartz and, more importantly, of organic compounds such as sugars or tartaric acid, was discovered in by the French scientist Jean-Baptiste Biot.

Chiral molecules can be classified based on the direction in which plane-polarized light is rotated when it passes through a solution containing them. Obviously, if we consider a pair of enantiomers, one is dextrorotatory and the other levorotatory.

At present it is not possible to reliably predict the magnitude, direction, or sign of the rotation of plane-polarized light caused by an enantiomer. On the other hand, the optical activity of a molecule provides no information on the spatial arrangement of the chemical groups attached to the chirality center.

Note: a system containing molecules that having the same chirality sense is called enantiomerically pure or enantiopure. After separating them with tweezers, Pasteur discovered that the solutions obtained by dissolving equimolar amounts of the two kind of crystals were optically active and, interestingly, the rotation angle of plane-polarized light was equal in magnitude but opposite in sign.

Because the differences in optical activity were due to the dissolved sodium ammonium tartrate crystals, Pasteur hypothesized that the molecules themselves should be non-superimposable mirror images of each other, like their crystals: they were what we now call enantiomers. And it is Pasteur who first used the term asymmetry to describe this property, then called chirality by Lord Kelvin.

A solution containing an equal amount of each member of a pair of enantiomers is called racemic mixture or racemate. These solutions are optically inactive : there is no net rotation of plane-polarized light since the amount of dextrorotatory and levorotatory molecules is exactly the same.

Unlike what happens in biochemical processes, the chemical synthesis of chiral molecules that does not involve chiral reactants, or that is not followed by methods of separation of enantiomers, inevitably leads to the production of a racemic mixture. Remember, all chiral structures may exist as a pair of enantiomers. Other configurational stereoisomers are possible if more than one stereogenic center is present in a structure.

Identifying and distinguishing enantiomers is inherently difficult, since their physical and chemical properties are largely identical. Fortunately, a nearly two hundred year old discovery by the French physicist Jean-Baptiste Biot has made this task much easier.

This discovery disclosed that the right- and left-handed enantiomers of a chiral compound perturb plane-polarized light in opposite ways. This perturbation is unique to chiral molecules, and has been termed optical activity.

Plane-polarized light is created by passing ordinary light through a polarizing device, which may be as simple as a lens taken from polarizing sun-glasses. Such devices transmit selectively only that component of a light beam having electrical and magnetic field vectors oscillating in a single plane.

The plane of polarization can be determined by an instrument called a polarimeter , shown in the diagram below. Monochromatic single wavelength light, is polarized by a fixed polarizer next to the light source. A sample cell holder is located in line with the light beam, followed by a movable polarizer the analyzer and an eyepiece through which the light intensity can be observed.

In modern instruments an electronic light detector takes the place of the human eye. Chemists use polarimeters to investigate the influence of compounds in the sample cell on plane polarized light.

Samples composed only of achiral molecules e. The prefixes dextro and levo come from the Latin dexter , meaning right, and laevus , for left, and are abbreviated d and l respectively. If equal quantities of each enantiomer are examined , using the same sample cell, then the magnitude of the rotations will be the same, with one being positive and the other negative. To be absolutely certain whether an observed rotation is positive or negative it is often necessary to make a second measurement using a different amount or concentration of the sample.

Since it is not always possible to obtain or use samples of exactly the same size, the observed rotation is usually corrected to compensate for variations in sample quantity and cell length.

Compounds that rotate the plane of polarized light are termed optically active. Each enantiomer of a stereoisomeric pair is optically active and has an equal but opposite-in-sign specific rotation. Specific rotations are useful in that they are experimentally determined constants that characterize and identify pure enantiomers.

For example, the lactic acid and carvone enantiomers discussed earlier have the following specific rotations. A mixture of enantiomers has no observable optical activity. Such mixtures are called racemates or racemic modifications, and are designated? When chiral compounds are created from achiral compounds, the products are racemic unless a single enantiomer of a chiral co-reactant or catalyst is involved in the reaction.

The addition of HBr to either cis- or transbutene is an example of racemic product formation the chiral center is colored red in the following equation. Chiral organic compounds isolated from living organisms are usually optically active, indicating that one of the enantiomers predominates often it is the only isomer present.

This is a result of the action of chiral catalysts we call enzymes, and reflects the inherently chiral nature of life itself. Chiral synthetic compounds, on the other hand, are commonly racemates, unless they have been prepared from enantiomerically pure starting materials. There are two ways in which the condition of a chiral substance may be changed: 1.

A racemate may be separated into its component enantiomers. This process is called resolution. A pure enantiomer may be transformed into its racemate.

This process is called racemization. Although enantiomers may be identified by their characteristic specific rotations, the assignment of a unique configuration to each has not yet been discussed. We have referred to the mirror-image configurations of enantiomers as "right-handed" and "left-handed", but deciding which is which is not a trivial task.

An early procedure assigned a D prefix to enantiomers chemically related to a right-handed reference compound and a L prefix to a similarly related left-handed group of enantiomers.

Although this notation is still applied to carbohydrates and amino acids, it required chemical transformations to establish group relationships, and proved to be ambiguous in its general application. A final solution to the vexing problem of configuration assignment was devised by three European chemists: R. Cahn, C. Ingold and V. In the CIP system of nomenclature, each chiral center in a molecule is assigned a prefix R or S , according to whether its configuration is right- or left-handed.

No chemical reactions or interrelationship are required for this assignment. The symbol R comes from the Latin rectus for right, and L from the Latin sinister for left. The sequence rule is the same as that used for assigning E-Z prefixes to double bond stereoisomers. Since most of the chiral stereogenic centers we shall encounter are asymmetric carbons, all four different substituents must be ordered in this fashion. The Sequence Rule for Assignment of Configurations to Chiral Centers Assign sequence priorities to the four substituents by looking at the atoms attached directly to the chiral center.

The higher the atomic number of the immediate substituent atom, the higher the priority. Different isotopes of the same element are assigned a priority according to their atomic mass. If two substituents have the same immediate substituent atom, evaluate atoms progressively further away from the chiral center until a difference is found.

If double or triple bonded groups are encountered as substituents, they are treated as an equivalent set of single-bonded atoms. Once the relative priorities of the four substituents have been determined, the chiral center must be viewed from the side opposite the lowest priority group. If we number the substituent groups from 1 to 4, with 1 being the highest and 4 the lowest in priority sequence, the two enantiomeric configurations are shown in the following diagram along with a viewers eye on the side opposite substituent 4.

Remembering the geometric implication of wedge and hatched bonds , an observer the eye notes whether a curved arrow drawn from the 1 position to the 2 location and then to the 3 position turns in a clockwise or counter-clockwise manner.

If the turn is clockwise, as in the example on the right, the configuration is classified R. If it is counter-clockwise, as in the left illustration, the configuration is S. Another way of remembering the viewing rule, is to think of the asymmetric carbon as a steering wheel. The bond to the lowest priority group 4 is the steering column, and the other bonds are spokes on the wheel.

If the wheel is turned from group 1 toward group 2, which in turn moves toward group 3, this would either negotiate a right turn R or a left turn S. This model is illustrated below for a right-handed turn, and the corresponding R -configurations of lactic acid and carvone are shown to its right. The stereogenic carbon atom is colored magenta in each case, and the sequence priorities are shown as light blue numbers.

Note that if any two substituent groups on a stereogenic carbon are exchanged or switched, the configuration changes to its mirror image. The sequence order of the substituent groups in lactic acid should be obvious, but the carvone example requires careful analysis.

The hydrogen is clearly the lowest priority substituent, but the other three groups are all attached to the stereogenic carbon by bonds to carbon atoms colored blue here. Two of the immediate substituent species are methylene groups CH 2 , and the third is a doubly-bonded carbon. Rule 3 of the sequence rules allows us to order these substituents. The carbon-carbon double bond is broken so as to give imaginary single-bonded carbon atoms the phantom atoms are colored red in the equivalent structure.

To establish the sequence priority of the two methylene substituents both are part of the ring , we must move away from the chiral center until a point of difference is located. Rule 3 is again used to evaluate the two cases. The carbonyl group places two oxygens one phantom on the adjacent carbon atom, so this methylene side is ranked ahead of the other. An interesting feature of the two examples shown here is that the R-configuration in both cases is levorotatory - in its optical activity.

It is important to remember that there is no simple or obvious relationship between the R or S designation of a molecular configuration and the experimentally measured specific rotation of the compound it represents. In order to determine the true or "absolute" configuration of an enantiomer, as in the cases of lactic acid and carvone reported here, it is necessary either to relate the compound to a known reference structure, or to conduct a rather complex X-ray analysis on a single crystal of the sample.