Homochirality

Homochirality is a uniformity of

Biological organisms easily discriminate between molecules with different chiralities. This can affect physiological reactions such as smell and taste. Carvone, a terpenoid found in essential oils, smells like mint in its L-form and caraway in its R-form.^{[8]: 494 [verification needed]} Limonene tastes like citrus when right-handed and pine when left-handed.^[9]: 168

Homochirality also affects the response to drugs. Thalidomide, in its left-handed form, cures morning sickness; in its right-handed form, it causes birth defects.^[9]: 168 Unfortunately, even if a pure left-handed version is administered, some of it can convert to the right-handed form in the patient.^[10] Many drugs are available as both a racemic mixture (equal amounts of both chiralities) and an enantiopure drug (only one chirality). Depending on the manufacturing process, enantiopure forms can be more expensive to produce than stereochemical mixtures.^[9]: 168

Chiral preferences can also be found at a macroscopic level. Snail shells can be right-turning or left-turning helices, but one form or the other is strongly preferred in a given species. In the edible snail Helix pomatia, only one out of 20,000 is left-helical.^{[11]: 61–62} The coiling of plants can have a preferred chirality and even the chewing motion of cows has a 10% excess in one direction.^[12]

Origins

Symmetry breaking

Theories for the origin of homochirality in the molecules of life can be classified as deterministic or based on chance depending on their proposed mechanism. If there is a relationship between cause and effect — that is, a specific chiral field or influence causing the mirror symmetry breaking — the theory is classified as deterministic; otherwise it is classified as a theory based on chance (in the sense of randomness) mechanisms.^[13]

Another classification for the different theories of the origin of biological homochirality could be made depending on whether life emerged before the enantiodiscrimination step (biotic theories) or afterwards (abiotic theories). Biotic theories claim 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]} If this was the case, remains of the extinct chirality sign should be found. Since this is not the case, nowadays biotic theories are no longer supported.

The emergence of chirality consensus as a natural autoamplification process has also been associated with the

In deterministic theories, the enantiomeric imbalance is created due to an external chiral field or influence, and the ultimate sign imprinted in biomolecules will be due to it. Deterministic mechanisms for the production of non-racemic mixtures from racemic starting materials include: asymmetric physical laws, such as the electroweak interaction (via cosmic rays^[15]) or asymmetric environments, such as those caused by circularly polarized light, quartz crystals, or the Earth's rotation, β-Radiolysis or the magnetochiral effect.^[16][17] The most accepted universal deterministic theory is the electroweak interaction. Once established, chirality would be selected for.^[18]

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 an enantiomeric excess within chiral material in space.^{[11]: 123–124} Interstellar and near-stellar magnetic fields can align dust particles in this fashion.^[19] 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.

Chance theories

Chance theories are based on the assumption that "Absolute asymmetric synthesis, i.e., the formation of enantiomerically enriched products from achiral precursors without the intervention of chiral chemical reagents or catalysts, is in practice unavoidable on statistical grounds alone".^[20]

Consider the racemic state as a macroscopic property described by a binomial distribution; the experiment of tossing a coin, where the two possible outcomes are the two enantiomers is a good analogy. The discrete probability distribution ${\displaystyle P_{p}(n,N)}$ of obtaining n successes out of ${\displaystyle N}$ Bernoulli trials, where the result of each Bernoulli trial occurs with probability ${\displaystyle p}$ and the opposite occurs with probability ${\displaystyle q=(1-p)}$ is given by:

${\displaystyle P_{p}(n,N)={\binom {N}{n}}p^{n}(1-p)^{N-n}}$ .

The discrete probability distribution ${\displaystyle P(N/2,N)}$ of having exactly ${\displaystyle N/2}$ molecules of one chirality and ${\displaystyle N/2}$ of the other, is given by:

${\displaystyle P_{1/2}(N/2,N)={\binom {N}{N/2}}\left({\frac {1}{2}}\right)^{N/2}\left({\frac {1}{2}}\right)^{N/2}\approx {\sqrt {\frac {2}{\pi N}}}}$ .

As in the experiment of tossing a coin, in this case, we assume both events (${\displaystyle L}$ or ${\displaystyle D}$) to be equiprobable, ${\displaystyle p=q=1/2}$. The probability of having exactly the same amount of both enantiomers is inversely proportional to the square root of the total number of molecules ${\displaystyle N}$. For one mol of a racemic compound, ${\displaystyle N=N_{A}\approx 6.022\cdot 10^{23}}$ molecules, this probability becomes ${\displaystyle P_{1/2}(N_{A}/2,N_{A})\approx 10^{-12}}$. The probability of finding the racemic state is so small that we can consider it negligible.

In this scenario, there is a need to amplify the initial stochastic enantiomeric excess through any efficient mechanism of amplification.^[4] The most likely path for this amplification step is by asymmetric autocatalysis. An autocatalytic chemical reaction is that in which the reaction product is itself a reactive, in other words, a chemical reaction is autocatalytic if the reaction product is itself the catalyst of the reaction. In asymmetric autocatalysis, the catalyst is a chiral molecule, which means that a chiral molecule is catalysing its own production. An initial enantiomeric excess, such as can be produced by polarized light, then allows the more abundant enantiomer to outcompete the other.

Amplification

Theory

In 1953, Charles Frank proposed a model to demonstrate that homochirality is a consequence of autocatalysis.^[21][22] In his model the L and D enantiomers of a chiral molecule are autocatalytically produced from an achiral molecule A

${\displaystyle {\begin{aligned}A+L\xrightarrow {k_{a}} 2L,\\A+D\xrightarrow {k_{a}} 2D,\end{aligned}}}$

while suppressing each other through a reaction that he called mutual antagonism

${\displaystyle {\begin{aligned}L+D\xrightarrow {k_{d}} \varnothing .\\\end{aligned}}}$

In this model the racemic state is unstable in the sense that the slightest enantiomeric excess will be amplified to a completely homochiral state. This can be shown by computing the reaction rates from the law of mass action:

${\displaystyle {\begin{aligned}{\frac {d[{\ce {L}}]}{dt}}&=k_{a}[{\ce {A}}][{\ce {L}}]-k_{d}{\ce {[L][D]}}\\{\frac {d[{\ce {D}}]}{dt}}&=k_{a}[{\ce {A}}][{\ce {D}}]-k_{d}{\ce {[L][D]}},\end{aligned}}}$

where ${\displaystyle k_{a}}$ is the rate constant for the autocatalytic reactions, ${\displaystyle k_{d}}$ is the rate constant for mutual antagonism reaction, and the concentration of A is kept constant for simplicity.

The analytical solutions for are found to be ${\displaystyle [L]/[D]=[L]_{0}/[D]_{0}\,e^{kd([L]_{0}-[D]_{0})(e^{k_{a}t}-1)}}$ . The ratio ${\displaystyle [L]/[D]}$ increases at a more than exponential rate if ${\displaystyle ([L]_{0}-[D]_{0})}$ is positive (and vice versa). Every starting conditions different to

${\displaystyle [L]_{0}=[D]_{0}}$ lead to one of the asymptotes ${\displaystyle [L]=0}$ or ${\displaystyle [D]=0}$. Thus the equality of ${\displaystyle [L]_{0}}$ and ${\displaystyle [D]_{0}}$ and so of ${\displaystyle [L]}$ and ${\displaystyle [D]}$ represents a condition of unstable equilibrium, this result depending on the presence of the term representing mutual antagonism.

By defining the enantiomeric excess ${\displaystyle ee}$ as

${\displaystyle ee={\frac {[{\ce {D}}]-[{\ce {L}}]}{[{\ce {D}}]+[{\ce {L}}]}},}$

the rate of change of enantiomeric excess can be calculated using chain rule from the rate of change of the concentrations of enantiomers L and D.

${\displaystyle {\frac {d(ee)}{dt}}=\left({\frac {2k_{d}{\ce {[L][D]}}}{[{\ce {D}}]+[{\ce {L}}]}}\right)ee.}$

Linear stability analysis of this equation shows that the racemic state ${\displaystyle ee=0}$ is unstable. Starting from almost everywhere in the concentration space, the system evolves to a homochiral state.

It is generally understood that autocatalysis alone does not yield to homochirality, and the presence of the mutually antagonistic relationship between the two enantiomers is necessary for the instability of the racemic mixture. However, recent studies show that homochirality could be achieved from autocatalysis in the absence of the mutually antagonistic relationship, but the underlying mechanism for symmetry-breaking is different.^[4][23]

Experiments

There are several laboratory experiments that demonstrate how a small amount of one enantiomer at the start of a reaction can lead to a large excess of a single enantiomer as the product. For example, the Soai reaction is autocatalytic.^[24][25] If the reaction is started with some of one of the product enantiomers already present, the product acts as an enantioselective catalyst for production of more of that same enantiomer.^[26] The initial presence of just 0.2 equivalent one enantiomer can lead to up to 93% enantiomeric excess of the product.

Another study^[27] concerns the proline catalyzed aminoxylation of propionaldehyde by nitrosobenzene. In this system, a small enantiomeric excess of catalyst leads to a large enantiomeric excess of product.

A high asymmetric amplification of the

Some proposed models for the transmission of chiral asymmetry are polymerization,[35]^{[36][37][38][39][40]} epimerization ^[41][42] or copolymerization.^[43][44]

Optical resolution in racemic amino acids

There exists no theory elucidating correlations among L-amino acids. If one takes, for example,

It was reported^[45] 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 = 100 ×(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.^[45] 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 of term

This term was introduced by

See also

• Chiral life concept
  - of artificially synthesizing chiral-mirror version of life
• CIP system
• Stereochemistry
• Pfeiffer Effect
• Unsolved problems in chemistry

References