Wikipedia

Absolute configuration

Inchemistry,absolute configurationrefers to the spatial arrangement ofatomswithin amolecular entity(orgroup) that ischiral,and its resultantstereochemicaldescription.[1]Absolute configuration is typically relevant inorganic moleculeswherecarbonis bonded to four differentsubstituents.This type of construction creates two possibleenantiomers.Absolute configuration uses a set of rules to describe the relative positions of each bond around the chiral center atom. The most common labeling method uses the descriptorsRorSand is based on theCahn–Ingold–Prelog priority rules.RandSrefer torectusandsinister,Latin for right and left, respectively.

Absolute configuration showing the determination of theRandSdescriptors

Chiral molecules can differ in their chemical properties, but are identical in their physical properties, which can make distinguishing enantiomers challenging. Absolute configurations for a chiral molecule (in pure form) are most often obtained byX-ray crystallography,although with some important limitations. All enantiomerically pure chiral molecules crystallise in one of the 65Sohncke groups(chiral space groups). Alternative techniques includeoptical rotatory dispersion,vibrational circular dichroism,ultraviolet-visible spectroscopy,the use ofchiral shift reagentsinproton NMRand Coulomb explosion imaging.[2][3]

History

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Until 1951, it was not possible to obtain the absolute configuration of chiral compounds. It was at some time arbitrarily decided that (+)-glyceraldehydewas theD-enantiomer.[4][5]The configuration of other chiral compounds was then related to that of (+)-glyceraldehyde by sequences ofchemical reactions.For example, oxidation of (+)-glyceraldehyde (1) withmercury oxidegives (−)-glyceric acid(2), a reaction that does not alter the stereocenter. Thus the absolute configuration of (−)-glyceric acid must be the same as that of (+)-glyceraldehyde. Oxidation of (+)-isoserine(3) bynitrous acidgives (−)-glyceric acid, establishing that (+)-isoserine also has the same absolute configuration.[6](+)-Isoserine can be converted by a two-stage process of bromination to (−)-3-bromo-2-hydroxy-propanoic acid (4) andzincreduction to give (−)-lactic acid(5), therefore (−)-lactic acid also has the same absolute configuration.[7]If a reaction gave the enantiomer of a known configuration, as indicated by the opposite sign of optical rotation, it would indicate that the absolute configuration is inverted.

In 1951,Johannes Martin Bijvoetfor the first time used inX-ray crystallographythe effect ofanomalous dispersion,which is now referred to asresonant scattering,to determine absolute configuration.[8]The compound investigated was (+)-sodium rubidiumtartrateand from its configuration (R,R) it was deduced that the original guess for (+)-glyceraldehyde was correct.

Despite the tremendous and unique impact on access to molecular structures, X-ray crystallography poses some challenges. The process of crystallization of the target molecules is time- and resource-intensive, and can not be applied to relevant systems of interest such as many biomolecules (some proteins are an exception) andin situcatalysts. Another important limitation is that the molecule must contain "heavy" atoms (for example, bromine) to enhance the scattering.[9]Furthermore, crucial distorsions of the signal arise from the influence of the nearest neighbors in anycrystal structureand of solvents used during thecrystallizationprocess.

Just recently, novel techniques have been introduced to directly investigate the absolute configuration of single molecules in gas-phase, usually in combination withab initioquantum mechanical theoretical calculations, therefore overcoming some of the limitations of the X-ray crystallography.[10]

Conventions

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By absolute configuration:R- andS-

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Examples of absolute configuration of some carbohydrates and amino acids according toFischer projection(D/Lsystem) andCahn–Ingold–Prelog priorityrules (R/Ssystem)

TheR/Ssystem is an important nomenclature system for denoting enantiomers. This approach labels each chiral centerRorSaccording to a system by which its substituents are each assigned apriority,according to theCahn–Ingold–Prelog priority rules(CIP), based on atomic number. When the center is oriented so that the lowest-priority substituent of the four is pointed away from the viewer, the viewer will then see two possibilities: if the priority of the remaining three substituents decreases in clockwise direction, it is labeledR(forLatin:rectus– right); if it decreases in counterclockwise direction, it isS(forLatin:sinister– left).[11]

(R) or (S) is written in italics and parentheses. If there are multiple chiral carbons, e.g. (1R,4S), a number specifies the location of the carbon preceding each configuration.[12]

TheR/Ssystem also has no fixed relation to theD/Lsystem. For example, the side-chain one ofserinecontains a hydroxyl group, −OH. If a thiol group, −SH, were swapped in for it, theD/Llabeling would, by its definition, not be affected by the substitution. But this substitution would invert the molecule'sR/Slabeling, 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, theD/Lsystem 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 the commonly occurring structures of a given type of structure in higher organisms. In theD/Lsystem, nearly all naturally occurring amino acids are allL,while naturally occurring carbohydrates are nearly allD.Allproteinogenic amino acidsareS,except forcysteine,which isR.

By optical rotation: (+)- and (−)- ord-andl-

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An enantiomer can be named by the direction in which it rotates the plane of polarized light. Clockwise rotation of the light traveling toward the viewer is labeled (+) enantiomer. Its mirror-image is labeled (−). The (+) and (−) isomers have been also termedd-andl-(fordextrorotatoryandlevorotatory); but, naming withd-andl-is easy to confuse withD- andL- labeling and is therefore discouraged byIUPAC.[13]

By relative configuration:D- andL-

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An optical isomer can be named by the spatial configuration of its atoms. TheD/Lsystem (named after Latin dexter and laevus, right and left), not to be confused with thed-andl-system,see above,does this by relating the molecule toglyceraldehyde.Glyceraldehyde is chiral itself and its two isomers are labeledDandL(typically typeset insmall capsin 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 acidalanine,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 (it's achiral).

TheD/Llabeling is unrelated to (+)/(−) – it does not indicate which enantiomer is dextrorotatory and which is levorotatory. Rather, it indicates the compound's stereochemistry relative to that of thedextrorotatoryorlevorotatoryenantiomer of glyceraldehyde. The dextrorotatory isomer of glyceraldehyde is, in fact, theD-isomer. Nine of the nineteenL-amino acids commonly found in proteins are dextrorotatory (at a wavelength of 589 nm), andD-fructose is also referred to as levulose because it is levorotatory. A rule of thumb for determining theD/Lisomeric form of an amino acid is the "CORN" rule. The groups

COOH,R,NH2and 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 theCO→R→Ngroups around the carbon atom as center is counter-clockwise, then it is theLform.[14]If the arrangement is clockwise, it is theDform. As usual, if the molecule itself is oriented differently, for example, with H towards the viewer, the pattern may be reversed. TheLform is the usual one found in natural proteins. For most amino acids, theLform corresponds to anSabsolute stereochemistry, but isRinstead for certain side-chains.

See also

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References

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  1. ^IUPAC,Compendium of Chemical Terminology,2nd ed. (the "Gold Book" ) (1997). Online corrected version: (2006–) "absolute configuration".doi:10.1351/goldbook.A00020
  2. ^"Snapshots differentiate molecules from their mirror image".mpg.de.Retrieved16 February2021.
  3. ^Pitzer, Martin; Kunitski, Maksim; Johnson, Allan S.; Jahnke, Till; Sann, Hendrik; Sturm, Felix; Schmidt, Lothar Ph. H.; Schmidt-Böcking, Horst; Dörner, Reinhard; Stohner, Jürgen; Kiedrowski, Julia; Reggelin, Michael; Marquardt, Sebastian; Schießer, Alexander; Berger, Robert; Schöffler, Markus S. (6 September 2013). "Direct Determination of Absolute Molecular Stereochemistry in Gas Phase by Coulomb Explosion Imaging".Science.341(6150): 1096–1100.Bibcode:2013Sci...341.1096P.doi:10.1126/science.1240362.ISSN0036-8075.PMID24009390.S2CID206549826.
  4. ^Roberts, John D.; Caserio, Marjorie C. (1977).Basic Principles of Organic Chemistry(2nd ed.). Menlo Park, CA: W. A. Benjamin, Inc. pp. 874–876.ISBN9780805383294.
    Erratum: on page 875 'Until 1956' should read 'Until 1951'
  5. ^Bruice, Paula Yurkanis (2014).Organic Chemistry(7th ed.). Upper Saddle River: Pearson Education, Inc. p. 1020.ISBN9780321803221.
  6. ^Solomons, T.W. Graham; Fryhle, Graig B. (2008).Organic Chemistry(9th ed.). Hoboken:John Wiley & Sons, Inc.p. 212.ISBN9780471684961.
  7. ^Bruice, Paula Yurkanis (2004).Organic Chemistry(4th ed.). Upper Saddle River: Pearson Education, Inc. p. 210.ISBN9780131407480.
  8. ^Bijvoet, J. M.; Peerdeman, A. F.; van Bommel, A. J. (August 1951). "Determination of the Absolute Configuration of Optically Active Compounds by Means of X-Rays".Nature.168(4268): 271–272.Bibcode:1951Natur.168..271B.doi:10.1038/168271a0.ISSN0028-0836.S2CID4264310.
  9. ^Haesler, J.; Schindelholz, I.; Riguet, E.; Bochet, C. G.; Hug, W. (March 2007)."Absolute configuration of chirally deuterated neopentane"(PDF).Nature.446(7135): 526–529.Bibcode:2007Natur.446..526H.doi:10.1038/nature05653.ISSN0028-0836.PMID17392783.S2CID4423560.
  10. ^Fehre, K.; Nalin, G.; Novikovskiy, N. M.; Grundmann, S.; Kastirke, G.; Eckart, S.; Trinter, F.; Rist, J.; Hartung, A.; Trabert, D.; Janke, Ch; Pitzer, M.; Zeller, S.; Wiegandt, F.; Weller, M.; Kircher, M.; Hofmann, M.; Schmidt, L. Ph H.; Knie, A.; Hans, A.; Ltaief, L. Ben; Ehresmann, A.; Berger, R.; Fukuzawa, H.; Ueda, K.; Schmidt-Böcking, H.; Williams, J. B.; Jahnke, T.; Dörner, R.; Demekhin, Ph V.; Schöffler, M. S. (2022). "A new route for enantio-sensitive structure determination by photoelectron scattering on molecules in the gas phase".Physical Chemistry Chemical Physics.24(43): 26458–26465.arXiv:2101.03375.Bibcode:2022PCCP...2426458F.doi:10.1039/D2CP03090J.PMID36305893.S2CID253183411.
  11. ^Andrew Streitwieser&Clayton H. Heathcock(1985).Introduction to Organic Chemistry(3rd ed.). Macmillan Publishing Company.
  12. ^Klein, David R. (2013-12-31).Organic Chemistry(2nd ed.). Wiley. p. 208.ISBN978-1118454312.
  13. ^Moss, G. P. (1 January 1996)."Basic terminology of stereochemistry (IUPAC Recommendations 1996)".Pure and Applied Chemistry.68(12): 2193–2222.doi:10.1351/pac199668122193.ISSN1365-3075.S2CID98272391.Retrieved16 February2021.
  14. ^"Nomenclature and Symbolism for Amino Acids and Peptides".Pure Appl. Chem.56(5): 595–624. 1984.doi:10.1351/pac198456050595.
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