Asymmetric autocatalysis and amplification of enantiomeric excess of a chiral molecule

Soai, Kenso; Shibata, Takanori; Morioka, Hiroshi; Choji, Kaori

doi:10.1038/378767a0

Cited by 1,005 publications

(678 citation statements)

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“…Because of the relation between mirror-symmetry breaking and dimer formation rates and stabilities, it is likely that the structure of the aromatic part of the pyrimidine carbaldehydes is of essential importance not only for the amplification of ee but also for the occurrence of spontaneous symmetry breaking. For instance, there was no chiral amplification observed with ferrocenyl or 3-pyridyl carbaldehydes (35,36), whereas the amplification effects increased from 3-quinolyl to 5-pyrimidinyl and 2-methylpyrimidinyl to 2-alkynyl-5-pyrimidinyl carbaldehydes (12,24,37,38). Mirror-symmetry breaking has been observed only with the bulkiest alkynyl aldehydes.…”

Section: Resultsmentioning

confidence: 99%

“…In 1995, Soai et al (12) reported an example of spontaneous chiral amplification in organic chemistry that resulted in the formation of an asymmetric carbon and that essentially proceeds under homogeneous reaction conditions (13). As outlined in Scheme 1, the Soai reaction involves the addition of diisopropylzinc (Z) to a prochiral pyrimidine carbaldehyde (A) yielding isopropylzinc alkoxide (R or S) that, after hydrolysis, is converted into a stable chiral pyrimidyl alkanol.…”

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confidence: 99%

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Mirror-symmetry breaking in the Soai reaction: A kinetic understanding

Islas

Lavabre

Grévy

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

127

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Kinetic modeling using nonlinear differential equations is proposed to analyze the spontaneous generation of enantiomeric excess in the autocatalytic addition of diisopropylzinc to prochiral pyrimidine carbaldehydes (Soai reaction). Our approach reproduces experimentally observed giant chiral amplification from an initial enantiomeric excess of <10 ؊6 % to >60%, high sensitivity and positive response to the presence of minute amounts of chiral initiator at concentrations <10 ؊14 M, and spontaneous absolute asymmetric synthesis from achiral starting conditions. From our numerical simulations using kinetic schemes derived from the Frank model, including stereospecific autocatalysis and mutual inhibition, we have shown that it is possible to reproduce the mirror-symmetry-breaking behavior of the Soai reaction under batch conditions leading to a bimodal enantiomeric product distribution. Mirror-symmetry breaking was found to be resistant to a loss of stereoselectivity up to 30%. While the mutual inhibition between enantiomers seems to originate from the presence of dimerization equilibria, the exact nature of the autocatalytic stereoselective process still remains to be revealed. From the kinetic viewpoint, simple autocatalysis involving monomers as the catalytic species is consistent with all reported experimental effects of the Soai reaction.alkylzinc addition ͉ autocatalysis ͉ chirality A symmetric synthesis usually requires the intervention of chiral chemical reagents or catalysts. Few examples are known in which the generation of enantiomerically enriched products occurs from achiral precursors without the involvement of such auxiliaries. These cases, known as absolute asymmetric synthesis (1, 2), have been mostly observed in the combination of spontaneous resolution and enantioselective catalysis (3) as well as by the influence of external chiral factors such as circularly polarized light (4) or vortex motion (5). Some cases were reported in which no obvious chiral inductor was used and, nevertheless, high enantiomeric excess (ee) has been obtained systematically. These examples display the signature of mirrorsymmetry breaking (6), i.e., a process in which a small random ee is greatly amplified, whereas the chirality sign remains unpredictable for each individual experiment. The generation of small random ee occurs practically in any chiral system for statistical reasons alone in which the ee is inversely proportional to the square root of the number of molecules, ee ϰ n Ϫ1/2 (7). However, this value remains negligible as long as a large number of molecules is involved, so an amplification mechanism is needed to increase such minute ee to a macroscopic level.Mirror-symmetry breaking in chemical systems is typically associated to autocatalytic kinetics, i.e., a feedback mechanism in which one or several reaction products directly increase the overall rate of the chemical reaction. Hence in the specific case of chiral autocatalysis, the enantiomeric product could act as an asymmetric catalyst of its proper forma...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Mirror-symmetry breaking in the Soai reaction: A kinetic understanding

Islas

Lavabre

Grévy

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

127

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“…This deceptively simple mathematical model of self-replication and mirror-image inhibition spurred decades of research seeking an experimental proof of concept, ultimately demonstrated by Soai and co-workers in 1995. 10 To date, the Soai reaction (see scheme in Fig. 1) remains the only documented experimental example of autocatalytic enantioenrichment, and the system has served a) blackmond@scripps.edu b) hochbergd@cab.inta-csic.es as a model for how homochirality might emerge.…”

Section: Introductionmentioning

confidence: 99%

Necessary conditions for the emergence of homochirality via autocatalytic self-replication

Stich

Ribó

Blackmond

et al. 2016

The Journal of Chemical Physics

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We analyze a recent proposal for spontaneous mirror symmetry breaking based on the coupling of first-order enantioselective autocatalysis and direct production of the enantiomers that invokes a critical role for intrinsic reaction noise. For isolated systems, the racemic state is the unique stable outcome for both stochastic and deterministic dynamics when the system is in compliance with the constraints dictated by the thermodynamics of chemical reaction processes. In open systems, the racemic outcome also results for both stochastic and deterministic dynamics when driving the autocatalysis unidirectionally by external reagents. Nonracemic states can result in the latter only if the reverse reactions are strictly zero: these are kinetically controlled outcomes for small populations and volumes, and can be simulated by stochastic dynamics. However, the stability of the thermodynamic limit proves that the racemic outcome is the unique stable state for strictly irreversible externally driven autocatalysis. These findings contradict the suggestion that the inhibition requirement of the Frank autocatalytic model for the emergence of homochirality may be relaxed in a noise-induced mechanism. Published by AIP Publishing. [http://dx

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“…It is important to view the significance of Soai's discovery (1) in the context of the intensive search that has taken place to find an experimental system that would confirm the theoretical conclusions concerning asymmetric amplification in autocatalysis outlined in Frank's 1953 paper (5). This work provided a ''simple and sufficient life model'' for a chemical rationalization of the evolution of high ee in organic molecules from a small initial imbalance, and Frank (5) concluded with these provocative words: ''A laboratory demonstration may not be impossible.''…”

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confidence: 99%

Asymmetric Autocatalysis and Its Implications for the Origin of Homochirality

Blackmond

2004

ChemInform

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An autocatalytic reaction in which the reaction product serves as a catalyst to produce more of itself and to suppress production of its enantiomer serves as a mechanistic model for the evolution of homochirality. The Soai reaction provided experimental confirmation of this concept, nearly 50 years after it was first proposed. This Perspective offers a rationalization of the Soai autocatalytic reaction; accounting for enantiomeric excess and rate observations, that is both simple as well as gratifying in its implications for the chemical origin of life.

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Asymmetric autocatalysis and amplification of enantiomeric excess of a chiral molecule

Cited by 1,005 publications

References 26 publications

Mirror-symmetry breaking in the Soai reaction: A kinetic understanding

Mirror-symmetry breaking in the Soai reaction: A kinetic understanding

Necessary conditions for the emergence of homochirality via autocatalytic self-replication

Asymmetric Autocatalysis and Its Implications for the Origin of Homochirality

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