Chirality (chemistry)

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Two enantiomers of a generic amino acid that is chiral
(S)-Alanine (left) and (R)-alanine (right) in zwitterionic form at neutral pH

Chirality/ˈkaɪərəl/ is a geometric property of some molecules and ions. A chiral molecule/ion is non-superposable on its mirror image. The presence of an asymmetric carbon atom is one of several structural features that induce chirality in organic and inorganic molecules.[1][page needed] [2][page needed] [3][4] The term chirality is derived from the Greek word for hand, χειρ (kheir).

The mirror images of a chiral molecule/ion are called enantiomers or optical isomers. Pairs of enantiomers are often designated as "right-" and "left-handed". Molecular chirality is an essential consideration when discussing the stereochemistry in inorganic chemistry and organic chemistry. The concept is of great practical importance because most biomolecules and pharmaceuticals are chiral.

History[edit]

The term optical activity is derived from the interaction of chiral materials with polarized light. In a solution, the (−)-form, or levorotatory form, of an optical isomer rotates the plane of a beam of linearly polarized light counterclockwise. The (+)-form, or dextrorotatory form, of an optical isomer does the opposite. The property was first observed by Jean-Baptiste Biot in 1815,[5] and gained considerable importance in the sugar industry, analytical chemistry, and pharmaceuticals. Louis Pasteur deduced in 1848 that this phenomenon has a molecular basis.[6][7] The term chirality itself was coined by Lord Kelvin in 1894.[8][better source needed] Different enantiomers or diastereomers of a compound were formerly called optical isomers due to their different optical properties.[9] At one time, chirality was thought to be associated with organic chemistry, but this misconception was overthrown by the resolution of a purely inorganic compound, hexol, by Alfred Werner.

Symmetry[edit]

Chirality is a statement about the symmetry of a molecule or ion. Specifically, chirality indicates the absence of an improper axis of rotation, which includes planes of symmetry and an inversion center. In the parlance of Group Theory, chiral molecules/ions lack σ and i symmetry elements. Chiral molecules are always dysymmetric (lacking σ and i) but not always asymmetric (lacking in all symmetry elements except the identity). Asymmetic molecules are always chiral.[10]

Commonly in organic chemistry, the stereogenic center is a tetrahedral carbon site with four different substituents. Such species are asymmetric and chiral.

Naming conventions[edit]

By configuration: R- and S-[edit]

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, Latin for right), if it decreases in counterclockwise direction, it is S (for Sinister, Latin for left).[11][page needed]

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 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 (−)- or d- and l-[edit]

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 and is therefore strongly discouraged by IUPAC.[12]

By configuration: D- and L-[edit]

An optical isomer can be named by the spatial configuration of its atoms. The D/L system (named after Latin dexter and laevus, right and left), not to be confused with the d- and l-system, see above, 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 chiral 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).

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 the side-chain)

are arranged around the chiral center carbon atom. With the hydrogen atom away from the viewer, if the arrangement of the CORN groups around the carbon atom as center is counter-clockwise, then it is the L form.[13] If the arrangement is clockwise, it is the D form. As usual, if the molecule itself is oriented differently, for example, with H towards the viewer, the pattern may be reversed. The L form is the usual one found in natural proteins. For most amino acids, the L form corresponds to an S absolute stereochemistry, but is R instead for certain side-chains.

Stereogenic centers[edit]

Main article: Stereogenic center

In general, chiral molecules have point chirality at a single stereogenic atom, 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 a tetrahedral atom has four different substituents it is chiral. However, in rare cases, if two of the ligands differ from each other by being mirror images of each other, 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 stereogenic centers without being chiral overall if there is a symmetry between the two (or more) stereocenters 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), 1,3-dichloro-allene, and BINAP, which have axial chirality, (E)-cyclooctene, which has planar chirality, and certain calixarenes and fullerenes, which have inherent chirality.

A form of point chirality can also occur if a molecule contains a tetrahedral subunit which cannot easily rearrange, for instance 1-bromo-1-chloro-1-fluoroadamantane and methylethylphenyltetrahedrane.

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°.[14][non-primary source needed]

The identity of the stereogenic atom[edit]

The stereogenic atom in chiral molecules is usually carbon, as in many biological molecules. However chirality can exist in any atom, including metals (as in many chiral coordination compounds), phosphorus, or sulfur. Chiral nitrogen is equally possible, although the effects of nitrogen inversion can make many of these compound impossible to isolate.

The chiral atom Carbon Nitrogen Phosphorus (phosphates) Phosphorus (phosphines) Sulfur Metal (type of metal)
1 stereogenic center Serine, glyceraldehyde Cyclanoline Sarin, VX Esomeprazole, armodafinil Tris(bipyridine)ruthenium(II) (ruthenium), cis-Dichlorobis(ethylenediamine)cobalt(III) (cobalt), hexol (cobalt)
2 stereogenic centers Threonine, isoleucine Tröger's base Adenosine triphosphate DIPAMP Dithionous acid
3 or more stereogenic centers Met-enkephalin, leu-enkephalin DNA

In biochemistry[edit]

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.[15][page needed] 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.[16][full citation needed]

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.

L-forms of amino acids tend to be tasteless, whereas D-forms tend to taste sweet.[15][page needed] Spearmint leaves contain the L-enantiomer of the chemical carvone or R-(–)-carvone and caraway seeds contain the D-enantiomer or S-(+)-carvone.[17] 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.[18]

Inorganic chemistry[edit]

Delta-ruthenium-tris(bipyridine) cation

Chirality is a symmetry property, not a characteristic of any part of the periodic table. Thus, many inorganic materials, molecules, and ions are chiral. Quartz is an example from the mineral kingdom. Such noncentric materials are of interest for applications in nonlinear optics.

In the areas of coordination chemistry and organometallic chemistry, chirality is pervasive and of practical importance. A famous example is tris(bipyridine)ruthenium(II) complex in which the three bipyridine ligands adopt a chiral propeller-like arrangement.[19] The two enantiomers of complexes such as [Ru(2,2′-bipyridine)3]2+ may be designated as Λ (capital lambda, the Greek version of "L") for a left-handed twist of the propeller described by the ligands, and Δ (capital delta, Greek "D") for a right-handed twist (pictured).

Chiral ligands confer chirality to a metal complex, as illustrated by metal-amino acid complexes. If the metal exhibits catalytic properties, its combination with a chiral ligand is the basis of asymmetric catalysis.[20]

Stereogenic lone pairs[edit]

Inversion of an ammonia molecule at nitrogen. The C3 axis of ammonia is presented as vertical.
Amine R-N.svg  ⇌  Amine N-R.svg
Inversion of a generic organic amine molecule at nitrogen. The C3 axis of the amine is presented as horizontal, and the pair of dots represent the lone pair of the nitrogen atom collinear with that axis. A mirror plane can be imagined to relate the two amine molecules on either side of the arrows. If the three R groups attached to the nitrogen are all unique, then the amine is chiral; whether it can be isolated depends on the free energy required for the molecule's inversion.

A nonbonding pair of electrons, a lone pair, can contribute to the existence of chirality in a molecule, when three other groups attached to an atom all differ.[citation needed] The effect is seen in certain amines, phosphines,[21][page needed] sulfonium and oxonium ions, sulfoxides, and even carbanions.[citation needed] Chiral phosphines are a further example of molecules displaying such properties as a result of lone pair contributions.[citation needed]

In the case of chiral amines, separation of enantiomers can be difficult, because the energy barrier for nitrogen inversion at the stereo center may be low, which can allow the two stereoisomers to rapidly interconvert at room temperature.[citation needed] As a result, such chiral amines cannot be resolved, unless the amine's groups are constrained in a cyclic structure (such as in Tröger's base),[citation needed] or some other circumstance contributes to an increased barrier to interconversion.[citation needed]

Methods and practices[edit]

Miscellaneous nomenclature[edit]

  • Any non-racemic chiral substance is called scalemic.[clarification needed][22]
  • A chiral substance is enantiopure or homochiral when only one of two possible enantiomers is present.[citation needed]
  • A chiral substance is enantioenriched or heterochiral when an excess of one enantiomer is present but not to the exclusion of the other.[citation needed]
  • 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%.[citation needed]

Further reading[edit]

The following are principle sources for the developing content in this article, that contain further information that may be of interest to readers. In the books listed, the material on chirality appears throughout, and so page numbers should be given for specific ideas and quotations drawn from them that are introduced above.

  • A high quality introductory to intermediate textbook of organic chemistry: Clayden, Jonathan ; Greeves, Nick & Warren, Stuart (2012). Organic Chemistry (2nd ed.). Oxford, UK: Oxford University Press. pp. 319f, 432, 604np, 653, 746int, 803ketals, 839, 846f. ISBN 0199270295. Retrieved 2 February 2016. 
  • A seminal, authoritative work on modern organic stereochemistry: Eliel, Ernest Ludwig; Wilen, Samuel H. & Mander, Lewis N. (1994). "Chirality in Molecules Devoid of Chiral Centers (Chapter 14)". Stereochemistry of Organic Compounds (1st ed.). New York, NY, USA: Wiley & Sons. ISBN 0471016705. Retrieved 2 February 2016.  For a further but less stable source of the same text that provides access to the relevant material, see Stereochemistry of Organic Compounds. ISBN 9780471016700. , same access date.
  • An important brief expert comment on misuse of stereochemical terms: Eliel, E.L. (1997). "Infelicitous Stereochemical Nomenclatures". chirality 9: 428–430. Retrieved 5 February 2016. Quoting: 'Misuse of current stereochemical terms is discussed, including terms that should be avoided altogether and replaced by other, standard ones. The reasons for using the proper terms and avoiding the infelicitous ones are pointed out.'   For a further but less stable source of the same text that provides access to the relevant material, see [2], same access date.
  • A recent review providing definitions, examples, and history: Gal, Joseph (2013). "Molecular Chirality: Language, History, and Significance". Differentiation of Enantiomers I. chirality. Topics in Current Chemistry 9. pp. 1–20. Retrieved 5 February 2016. 

See also[edit]

References[edit]

  1. ^ Organic Chemistry (4th Edition) Paula Y. Bruice.[full citation needed]
  2. ^ Organic Chemistry (3rd Edition) Marye Anne Fox ,James K. Whitesell.[full citation needed]
  3. ^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version:  (2006–) "Chirality".
  4. ^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version:  (2006–) "Superposability".
  5. ^ Lakhtakia, A. (ed.) (1990). Selected Papers on Natural Optical Activity (SPIE Milestone Volume 15). SPIE. [full citation needed]
  6. ^ Pasteur, L. (1848). "Researches on the molecular asymmetry of natural organic products, English translation of French original, published by Alembic Club Reprints (Vol. 14, pp. 1–46) in 1905, facsimile reproduction by SPIE in a 1990 book". 
  7. ^ Eliel, Ernest Ludwig; Wilen, Samuel H. & Mander, Lewis N. (1994). "Chirality in Molecules Devoid of Chiral Centers (Chapter 14)". Stereochemistry of Organic Compounds (1st ed.). New York, NY, USA: Wiley & Sons. ISBN 0471016705. Retrieved 2 February 2016.  For a further but less stable source of the same text that provides access to the relevant material, see [1], same access date.
  8. ^ Bentley, Ronald (1995). "From Optical Activity in Quartz to Chiral Drugs: Molecular Handedness in Biology and Medicine.". Perspect. Biol. Med. 38 (2): 188–229. doi:10.1353/pbm.1995.0069. PMID 7899056. Retrieved 2 February 2016. 
  9. ^ IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version:  (2006–) "Optical isomers".
  10. ^ Cotton, F. A., "Chemical Applications of Group Theory," John Wiley & Sons: New York, 1990.
  11. ^ Andrew Streitwieser & Clayton H. Heathcock (1985). Introduction to Organic Chemistry (3rd ed.). Macmillan Publishing Company. [full citation needed]
  12. ^ G.P. Moss: Basic terminology of stereochemistry ( Recommendations 1996); Pure Appl. Chem., 1996, Vol. 68, No. 12, p. 2205; doi:10.1351/pac199668122193
  13. ^ "Nomenclature and Symbolism for Amino Acids and Peptides". Pure Appl Chem 56 (5): 595–624. 1984. doi:10.1351/pac198456050595. 
  14. ^ ^ Streitwieser, A., Jr.; Wolfe, J. R., Jr.; Schaeffer, W. D. (1959). "Stereochemistry of the Primary Carbon. X. Stereochemical Configurations of Some Optically Active Deuterium Compounds". Tetrahedron 6 (4): 338–344. doi:10.1016/0040-4020(59)80014-4. [non-primary source needed]
  15. ^ a b Meierhenrich, Uwe J. (2008). Amino acids and the Asymmetry of Life. Berlin, GER: Springer. ISBN 3540768858. [page needed]
  16. ^ McKee, Maggie (2005-08-24). "Space radiation may select amino acids for life". New Scientist. Retrieved 2016-02-05. 
  17. ^ Theodore J. Leitereg, Dante G. Guadagni, Jean Harris, Thomas R. Mon, and Roy Teranishi (1971). "Chemical and sensory data supporting the difference between the odors of the enantiomeric carvones". J. Agric. Food Chem. 19 (4): 785–787. doi:10.1021/jf60176a035. 
  18. ^ Srinivasarao, M. (1999). "Chirality and Polymers". Current Opinion in Colloid and Interface Science 4 (5): 369–376. [full citation needed]
  19. ^ von Zelewsky, A. (1995). Stereochemistry of Coordination Compounds. Chichester: John Wiley.. ISBN 047195599X.[full citation needed]
  20. ^ Hartwig, J. F. Organotransition Metal Chemistry, from Bonding to Catalysis; University Science Books: New York, 2010. ISBN 189138953X
  21. ^ Quin, L. D. (2000). A Guide to Organophosphorus Chemistry, LOCATION: John Wiley & Sons. PAGES. ISBN 0471318248.[full citation needed]
  22. ^ Eliel, E.L. (1997). "Infelicitous Stereochemical Nomenclatures". Chirality 9: 428–430. Retrieved 5 February 2016. 

External links[edit]