Chirality (chemistry)


In chemistry, a molecule or ion is called chiral if it cannot be superposed on its mirror image by any combination of rotations, translations, and some conformational changes. This geometric property is called chirality. The terms are derived from Ancient Greek 'hand'; which is the canonical example of an object with this property.
A chiral molecule or ion exists in two stereoisomers that are mirror images of each other, called enantiomers; they are often distinguished as either "right-handed" or "left-handed" by their absolute configuration or some other criterion. The two enantiomers have the same chemical properties, except when reacting with other chiral compounds. They also have the same physical properties, except that they often have opposite optical activities. A homogeneous mixture of the two enantiomers in equal parts, a racemic mixture, differs chemically and physically from the pure enantiomers.
Chiral molecules will usually have a stereogenic element from which chirality arises. The most common type of stereogenic element is a stereogenic center, or stereocenter. In the case of organic compounds, stereocenters most frequently take the form of a carbon atom with four distinct groups attached to it in a tetrahedral geometry. Less commonly, other atoms like N, P, S, and Si can also serve as stereocenters, provided they have four distinct substituents attached to them.
A given stereocenter has two possible configurations, which give rise to stereoisomers in molecules with one or more stereocenter. For a chiral molecule with one or more stereocenter, the enantiomer corresponds to the stereoisomer in which every stereocenter has the opposite configuration. An organic compound with only one stereogenic carbon is always chiral. On the other hand, an organic compound with multiple stereogenic carbons is typically, but not always, chiral. In particular, if the stereocenters are configured in such a way that the molecule can take a conformation having a plane of symmetry or an inversion point, then the molecule is achiral and is known as a meso compound.
Molecules with chirality arising from one or more stereocenters are classified as possessing central chirality. There are two other types of stereogenic elements that can give rise to chirality, a stereogenic axis and a stereogenic plane. Finally, the inherent curvature of a molecule can also give rise to chirality. These types of chirality are far less common than central chirality. BINOL is a typical example of an axially chiral molecule, while trans-cyclooctene is a commonly cited example of a planar chiral molecule. Finally, helicene possesses helical chirality, which is one type of inherent chirality.
Chirality is an important concept for stereochemistry and biochemistry. Most substances relevant to biology are chiral, such as carbohydrates, all but one of the amino acids that are the building blocks of proteins, and the nucleic acids. Naturally occurring triglycerides are often chiral, but not always. In living organisms, one typically finds only one of the two enantiomers of a chiral compound. For that reason, organisms that consume a chiral compound usually can metabolize only one of its enantiomers. For the same reason, the potencies or effects of enantiomers of a pharmaceutical can differ sharply.

Definition

The chirality of a molecule is based on the molecular symmetry of its conformations. A conformation of a molecule is chiral if and only if it belongs to the Cn, Dn, T, O, or I point groups. However, whether the molecule itself is considered to be chiral depends on whether its chiral conformations are persistent isomers that could be isolated as separated enantiomers, at least in principle, or the enantiomeric conformers rapidly interconvert at a given temperature and timescale through low-energy conformational changes. For example, despite having chiral gauche conformers that belong to the C2 point group, butane is considered achiral at room temperature because rotation about the central C–C bond rapidly interconverts the enantiomers. Similarly, cis-1,2-dichlorocyclohexane consists of chair conformers that are nonidentical mirror images, but the two can interconvert via the cyclohexane chair flip. As another example, amines with three distinct substituents are also regarded as achiral molecules because their enantiomeric pyramidal conformers rapidly undergo pyramidal inversion.
However, if the temperature in question is low enough, the process that interconverts the enantiomeric chiral conformations becomes slow compared to a given timescale. The molecule would then be considered to be chiral at that temperature. The relevant timescale is, to some degree, arbitrarily defined: 1000 seconds is sometimes employed, as this is regarded as the lower limit for the amount of time required for chemical or chromatographic separation of enantiomers in a practical sense. Molecules that are chiral at room temperature due to restricted rotation about a single bond are said to exhibit atropisomerism.
A chiral compound can contain no improper axis of rotation, which includes planes of symmetry and inversion center. Chiral molecules are always dissymmetric but not always asymmetric. Asymmetric molecules are always chiral.
The following table shows some examples of chiral and achiral molecules, with the Schoenflies notation of the point group of the molecule. In the achiral molecules, X and Y represent achiral groups, whereas X and X or Y and Y represent enantiomers. Note that there is no meaning to the orientation of an S axis, which is just an inversion. Any orientation will do, so long as it passes through the center of inversion. Also note that higher symmetries of chiral and achiral molecules also exist, and symmetries that do not include those in the table, such as the chiral C or the achiral S.
An example of a molecule that does not have a mirror plane or an inversion and yet would be considered achiral is 1,1-difluoro-2,2-dichlorocyclohexane. This may exist in many conformers, but none of them has a mirror plane. In order to have a mirror plane, the cyclohexane ring would have to be flat, widening the bond angles and giving the conformation a very high energy. This compound would not be considered chiral because the chiral conformers interconvert easily.
An achiral molecule having chiral conformations could theoretically form a mixture of right-handed and left-handed crystals, as often happens with racemic mixtures of chiral molecules, or as when achiral liquid silicon dioxide is cooled to the point of becoming chiral quartz.

Stereogenic centers

A stereogenic center is an atom such that swapping the positions of two ligands on that atom results in a molecule that is stereoisomeric to the original. For example, a common case is a tetrahedral carbon bonded to four distinct groups a, b, c, and d, where swapping any two groups leads to a stereoisomer of the original, so the central C is a stereocenter. Many chiral molecules have point chirality, namely a single chiral stereogenic center that coincides with an atom. This stereogenic center usually has four or more bonds to different groups and may be carbon, phosphorus, silicon, or a metal. However, a stereogenic center can also be a trivalent atom whose bonds are not in the same plane, such as phosphorus in P-chiral phosphines and sulfur in S-chiral sulfoxides, because a lone-pair of electrons is present instead of a fourth bond.
Similarly, a stereogenic axis is defined as an axis in the molecule such that the swapping of any two ligands attached to the axis gives rise to a stereoisomer. For instance, the C2-symmetric species 1,1′-bi-2-naphthol and 1,3-dichloroallene have stereogenic axes and exhibit axial chirality, while -cyclooctene and many ferrocene derivatives bearing two or more substituents have stereogenic planes and exhibit planar chirality.
Chirality can also arise from isotopic differences between substituents, such as in the deuterated benzyl alcohol PhCHDOH; which is chiral and optically active, even though the non-deuterated compound PhCH2OH is not.
If two enantiomers easily interconvert, the pure enantiomers may be practically impossible to separate, and only the racemic mixture is observable. This is the case, for example, of most amines with three different substituents, because of the low energy barrier for nitrogen inversion.
When the optical rotation for an enantiomer is too low for practical measurement, the species is said to exhibit cryptochirality.
Chirality is an intrinsic part of the identity of a molecule, so the systematic name includes details of the absolute configuration.

Manifestations of chirality

Many biologically active molecules are chiral, including the naturally occurring amino acids and sugars.
The origin of this homochirality in biology is the subject of much debate. 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 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.
Enzymes, which are chiral, often distinguish between the two enantiomers of a chiral substrate. One could 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.
-forms of amino acids tend to be tasteless, whereas -forms tend to taste sweet. Spearmint leaves contain the -enantiomer of the chemical carvone or R--carvone and caraway seeds contain the -enantiomer or S--carvone. The two smell different to most people because our olfactory receptors are chiral.
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 transforms that phase to a chiral nematic phase. Chirality in context of such phases in polymeric fluids has also been studied in this context.