Chirality (chemistry)

Two enantiomers of a generic amino acid

(S)-Alanine (left) and (R)-alanine (right) in zwitterionic form at neutral pH

A chiral molecule is a type of molecule that lacks an internal plane of symmetry and has a non-superimposable 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 (pronounced /ˈkaɪrəl/) in general is used to describe an object that is non-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 (cheir). 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.

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,^[3] and gained considerable importance in the sugar industry, analytical chemistry, and pharmaceuticals. Louis Pasteur deduced in 1848 that this phenomenon has a molecular basis.^[4] Artificial composite materials displaying the analog of optical activity but in the microwave region were introduced by J.C. Bose in 1898,^[5] and gained considerable attention from the mid-1980s.^[6] The term chirality itself was coined by Lord Kelvin in 1873.^[7]

The word "racemic" (mix of both chiralities) is derived from the Latin word "racemus" for "bunch of grapes"; the term having its origins in the work of Louis Pasteur who isolated racemic tartaric acid from wine.

Symmetry

The symmetry of a molecule (or any other object) determines whether it is chiral. A molecule is achiral (not chiral) when an improper rotation, that is a combination of a rotation and a reflection in a plane, perpendicular to the axis of rotation, results in the same molecule - see chirality (mathematics). An equivalent definition is that a chiral molecule lacks a plane of symmetry. For tetrahedral molecules, the molecule is chiral if all four substituents are different.
A chiral molecule is not necessarily asymmetric (devoid of any symmetry element), as it can have, for example, rotational symmetry.

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 nearly all consistent - naturally occurring amino acids are nearly all l, while naturally occurring carbohydrates are nearly all d. 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). Naming with d- and l- is easy to confuse with d- and l- labeling.

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 (typically typeset in small caps in published work). 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.^[8]
• 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%.

Stereogenic centers

In general, chiral molecules have point chirality at a single stereogenic 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).

Normally when an atom has four different substituents, it is chiral. However in rare cases, two of the ligands differ from each other by being mirror images of each other. When this happens, the mirror image of the molecule is identical to the original, and the molecule is achiral. This is called pseudochirality.

A molecule can have multiple chiral centers without being chiral overall if there is a symmetry between the two (or more) chiral centers themselves. 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, (E)-cyclooctene, which has planar chirality, and certain calixarenes and fullerenes, which have inherent chirality.

It is important to keep in mind that molecules have considerable flexibility and thus, depending on the medium, may adopt a variety of different conformations. These various conformations are themselves almost always chiral. When assessing chirality, a time-averaged structure is considered and for routine compounds, one should refer to the most symmetric possible conformation.

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°.^[9]

Properties of enantiomers

Normally, the two enantiomers of a molecule behave identically to each other. For example, they will migrate with identical R_f in thin layer chromatography and have identical retention time in HPLC. Their NMR and IR spectra are identical. However, enantiomers behave differently in the presence of other chiral molecules or objects. For example, enantiomers do not migrate identically on chiral chromatographic media, such as quartz or standard media that have been chirally modified. The NMR spectra of enantiomers are affected differently by single-enantiomer chiral additives such as Eufod.

Chiral compounds rotate plane polarized light. Each enantiomer will rotate the light in a different sense, clockwise or counterclockwise. Molecules that do this are said to be optically active.

Characteristically, different enantiomers of chiral compounds often taste and smell differently and have different effects as drugs – see below. These effects reflect the chirality inherent in biological systems.

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.^[10] 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. However, there is some suggestion that early amino acids could have formed in comet dust. In this case, circularly polarised radiation (which makes up 17% of stellar radiation) could have caused the selective destruction of one chirality of amino acids, leading to a selection bias which ultimately resulted in all life on Earth being homochiral.^[11]

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.^[12]

In inorganic chemistry

Main article: Complex Chemistry

Many coordination compounds are chiral; for example, the well-known tris(bipyridine)ruthenium(II) complex in which the three bipyridine ligands adopt a chiral propeller-like arrangement.^[13]

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 as in Tröger's base.

See also

• Stereochemistry for overview of stereochemistry in general
• Axial chirality
• Supramolecular chirality
• Inherent chirality
• Chirality (physics)
• Chirality (mathematics)
• Pfeiffer Effect
• Chemical chirality in popular fiction

References

External links

• http://www.chirality2009.org/
• http://www.chemguide.co.uk/basicorg/isomerism/optical.html#top
• http://www.nature.com/horizon/chemicalspace/highlights/s5_nonspec1.html
• IUPAC nomenclature for amino acid configurations.
• Michigan State University's explanation of R/S nomenclature
• Chirality & Odour Perception at leffingwell.com
• Chirality & Bioactivity I.: Pharmacology
• Chirality and the Search for Extraterrestrial Life