Homochirality

Homochirality is a term used to refer to a group of molecules that possess the same sense of chirality. Molecules involved are not necessarily the same compound, but similar groups are arranged in the same way around a central atom. In biology homochirality is found in the chemical building blocks of life, the amino acids and sugars. All amino acids encoded by the genetic code have the same configuration about the chiral center, and are labeled S, with the exception of cysteine, which is labeled R only because the sulfur in the side chain changes the priority of that group. Typically, the alternative form is inactive and sometimes even toxic to living things. The origin of this phenomenon is not clearly understood. It is unclear if homochirality has a purpose, however it appears to be a form of information storage. ^[1] One suggestion is that it reduces entropy barriers in the formation of large organized molecules.^[2] It has been experimentally verified that amino acids form large aggregates in larger abundance from enantiopure substrates than from racemic ones.

Homochirality is said to evolve in three distinct steps: mirror-symmetry breaking creates a minute enantiomeric imbalance and is key to homochirality, chiral amplification is a process of enantiomeric enrichment and chiral transmission allows the transfer of chirality of one set of molecules to another.

It is also entirely possible that homochirality is simply a result of the natural autoamplification process of life—that either the formation of life as preferring one chirality or the other was a chance rare event which happened to occur with the chiralities we observe, or that all chiralities of life emerged rapidly but due to catastrophic events and strong competition, the other unobserved chiral preferences were wiped out by the preponderance and metabolic, enantiomeric enrichment from the 'winning' chirality choices^{[citation needed]}. The emergence of chirality consensus as a natural autoamplification process has been associated with the 2nd law of thermodynamics.^[3]

Mirror-symmetry breaking

Explaining how an enantiomeric imbalance is created in the first place is a difficult question to answer, but there are some attempts to solve this problem.^[4]

One supposition is that the discovery of an enantiomeric imbalance in molecules in the Murchison meteorite supports an extraterrestrial origin of homochirality: there is evidence for the existence of circularly polarized light originating from Mie scattering on aligned interstellar dust particles which may trigger the formation of optical isomers in space.^[5] Another speculation (the Vester-Ulbricht hypothesis) suggests that fundamental chirality of physical processes such as that of the beta decay (see Parity violation) leads to slightly different half-lives of biologically relevant molecules. Homochirality may also result from spontaneous absolute asymmetric synthesis.

Chiral amplification

Laboratory experiments exist demonstrating how in certain autocatalytic reaction systems the presence of a small amount of reaction product with enantiomeric excess at the start of the reaction can result in a much larger enantiomeric excess at the end of the reaction. In the Soai reaction,^[6] pyrimidine-5-carbaldehyde (Scheme 1) is alkylated by diisopropylzinc to the corresponding pyrimidyl alcohol. Because the initial reaction product is also an effective catalyst the reaction is autocatalytic. The presence of just 0.2 equivalent of the alcohol S-enantiomer at the start of the reaction is sufficient to amplify the enantiomeric excess to 93%.

Another study^[7] concerns the proline catalyzed aminoxylation of propionaldehyde by nitrosobenzene (scheme 2). In this system too the presence of enantioenriched catalyst drives the reaction towards one of the two possible optical isomers.

Serine octamer clusters^[8][9] are also contenders. These clusters of 8 serine molecules appear in mass spectrometry with an unusual homochiral preference, however there is no evidence that such clusters exist under non-ionizing conditions and amino acid phase behavior is far more prebiotically relevant.^[10] The recent observation that partial sublimation of a 10% enantioenriched sample of leucine results in up to 82% enrichment in the sublimate shows that enantioenrichment of amino acids could occur in space.^[11] Partial sublimation processes can take place on the surface of meteors where large variations in temperature exist. This finding may have consequences for the development of the Mars Organic Detector scheduled for launch in 2013 which aims to recover trace amounts of amino acids from the Mars surface exactly by a sublimation technique.

A high asymmetric amplification of the enantiomeric excess of sugars are also present in the amino acid catalyzed asymmetric formation of carbohydrates^[12]

One classic study involves an experiment that takes place in the laboratory.^[13] When sodium chlorate is allowed to crystallize from water and the collected crystals examined in a polarimeter, each crystal turns out to be chiral and either the L form or the D form. In an ordinary experiment the amount of L crystals collected equals the amount of D crystals (corrected for statistical effects). However when the sodium chlorate solution is stirred during the crystallization process the crystals are either exclusively L or exclusively D. In 32 consecutive crystallization experiments 14 experiments deliver D-crystals and 18 others L-crystals. The explanation for this symmetry breaking is unclear but is related to autocatalysis taking place in the nucleation process.

In a related experiment, a crystal suspension of a racemic amino acid derivative continuously stirred, results in a 100% crystal phase of one of the enantiomers because the enantiomeric pair is able to equilibrate in solution (compare with dynamic kinetic resolution)^[14]

Chiral transmission

Many strategies in asymmetric synthesis are built on chiral transmission. Especially important is the so-called organocatalysis of organic reactions by proline for example in Mannich reactions.

Optical resolution in racemic amino acids

There exists no theory elucidating correlations among L-amino acids. If one takes, for example, alanine, which has a small methyl group, and phenylalanine, which has a larger benzyl group, a simple question is in what aspect, L-alanine resembles L-phenylalanine more than D-phenylalanine, and what kind of mechanism causes the selection of all L-amino acids. Because it might be possible that alanine was L and phenylalanine was D.

It was reported^[15] in 2004 that excess racemic D,L-asparagine (Asn), which spontaneously forms crystals of either isomer during recrystallization, induces asymmetric resolution of a co-existing racemic amino acid such as arginine (Arg), aspartic acid (Asp), glutamine (Gln), histidine (His), leucine (Leu), methionine (Met), phenylalanine (Phe), serine (Ser), valine (Val), tyrosine (Tyr), and tryptophan (Trp). The enantiomeric excess {ee=100x(L-D)/(L+D)} of these amino acids was correlated almost linearly with that of the inducer, i.e., Asn. When recrystallizations from a mixture of 12 D,L-amino acids (Ala, Asp, Arg, Glu, Gln, His, Leu, Met, Ser, Val, Phe, and Tyr) and excess D,L-Asn were made, all amino acids with the same configuration with Asn were preferentially co-crystallized.^[15] It was incidental whether the enrichment took place in L- or D-Asn, however, once the selection was made, the co-existing amino acid with the same configuration at the α-carbon was preferentially involved because of thermodynamic stability in the crystal formation. The maximal ee was reported to be 100%. Based on these results, it is proposed that a mixture of racemic amino acids causes spontaneous and effective optical resolution, even if asymmetric synthesis of a single amino acid does not occur without an aid of an optically active molecule.

This is the first study elucidating reasonably the formation of chirality from racemic amino acids with experimental evidences.

History

This term was introduced by Kelvin in 1904, the year that published his Baltimore Lecture of 1884.^[12][16] Recently, however, homochiral has been used in the same sense as enantiomerically pure. This is permitted in some journals (but not encouraged), its meaning changing into the preference of a process or system for a single optical isomer in a pair of isomers in these journals.

See also

• Stereochemistry
• Unsolved problems in chemistry
• CIP system
• Chirality (biology)
• Pfeiffer Effect

References

1. ^ (2009), A New Definition of Life, Carroll, J. D. Chirality, 21: 354–358, 2009. doi: 10.1002/chir.20590
2. ^ Do Homochiral Aggregates Have an Entropic Advantage? Julian, R. R.; Myung, S.; Clemmer, D. E. J. Phys. Chem. B.; (Article); 2005; 109(1); 440-444. doi:10.1021/jp046478x
3. ^ Jaakkola, S., Sharma, V. and Annila, A. (2008). "Cause of chirality consensus". Curr. Chem. Biol. 2 (2): 53–58. doi:10.2174/187231308784220536. http://www.ingentaconnect.com/content/ben/ccb/2008/00000002/00000002/art00005. 
4. ^ Возможно ли спонтанное возникновение асимметрии в химической реакции?
5. ^ Uwe Meierhenrich. Amino Acids and the Asymmetry of Life; (Book) Springer-Verlag; 2008. ISBN 978-3-540-76885-2
6. ^ Takanori Shibata, Hiroshi Morioka, Tadakatsu Hayase, Kaori Choji, and Kenso Soai (1996). "Highly Enantioselective Catalytic Asymmetric Automultiplication of Chiral Pyrimidyl Alcohol". J. Am. Chem. Soc. 118 (2): 471–472. doi:10.1021/ja953066g. 
7. ^ Suju P. Mathew, Hiroshi Iwamura and Donna G. Blackmond (21 June 2004). "Amplification of Enantiomeric Excess in a Proline-Mediated Reaction". Angewandte Chemie International Edition 43 (25): 3317–3321. doi:10.1002/anie.200453997. PMID 15213963. 
8. ^ Cooks, R. G., Zhang, D., Koch, K. J. (2001). "Chiroselective Self-Directed Octamerization of Serine: Implications for Homochirogenesis". Anal. Chem. 73 (15)): 3646–3655. doi:10.1021/ac010284l. PMID 11510829. 
9. ^ Nanita, S., Cooks, R. G. (2006). "Serine Octamers: Cluster Formation, Reactions, and Implications for Biomolecule Homochirality". Angew. Chem. Int. Ed. 45 (4): 554–569. doi:10.1002/anie.200501328. PMID 16404754. 
10. ^ Donna G. Blackmond and Martin Klussmann (2007). "Spoilt for choice: assessing phase behaviour models for the evolution of homochirality". Chem. Commun. (39): 3990–3996. doi:10.1039/b709314b. PMID 17912393. 
11. ^ Stephen P. Fletcher, Richard B. C. Jagt and Ben L. Feringa (2007). "An astrophysically relevant mechanism for amino acid enantiomer enrichment". Chem. Commun. 2007 (25): 2578–2580. doi:10.1039/b702882b. PMID 17579743. 
12. ^ ^{a b} Armando Córdova, Magnus Engqvist, Ismail Ibrahem, Jesús Casas, Henrik Sundén (2005). "Plausible origins of homochirality in the amino acid catalyzed neogenesis of carbohydrates". Chem. Commun. 15: 2047–2049. 
13. ^ Kondepudi, D. K., Kaufman, R. J. & Singh, N. (1990). "Chiral Symmetry Breaking in Sodium Chlorate Crystallization". Science 250 (4983): 975–976. doi:10.1126/science.250.4983.975. PMID 17746924. 
14. ^ Emergence of a Single Solid Chiral State from a Nearly Racemic Amino Acid Derivative Wim L. Noorduin, Toshiko Izumi, Alessia Millemaggi, Michel Leeman, Hugo Meekes, Willem J. P. Van Enckevort, Richard M. Kellogg, Bernard Kaptein, Elias Vlieg, and Donna G. Blackmond J. Am. Chem. Soc.; 2008; 130(4) pp 1158 - 1159; (Communication) doi:10.1021/ja7106349
15. ^ ^{a b} S. Kojo, H. Uchino, M. Yoshimura, and K. Tanaka (2004). "Racemic D,L-asparagine causes enantiomeric excess of other coexisting racemic D,L-amino acids during recrystallization: a hypothesis accounting for the origin of L-amino acids in the biosphere.". Chem. Comm. (19): 2146–2147. doi:10.1039/b409941a. PMID 15467844. 
16. ^ Stereochemistry David G. Morris, Cambridge : Royal Society of Chemistry, 2001, p30.

External links

• On the Genesis of Homochirality A. Maureen Rouhi Chemical & Engineering News June 17, 2004 Link
• Observations Support Homochirality Theory Photonics TechnologyWorld November 1998 Link
• Scienceweek digest 1998 Link
• How left-handed amino acids got ahead: a demonstration of the evolution of biological homochirality in the lab Press release Imperial College London 2004 Link
• Origins of Homochirality conference in Nordita Stockholm, February 2008, talks available online [1]