Chiral autocatalytic processes

Kondepudi (2000) from Wake Forest University in Winston-Salem obtained some results which appeared sensational when crystallising a mixture of dissolved NaClC>3 and NaBrC>3 with stirring, an excess of one enantiomeric form (up to 80%) was formed. Prediction of which enantiomer will be in excess is not possible it is a matter of chance. The process is probably due to chiral autocatalytic processes similar phenomena were observed in melts. 

It is noteworthy that, as early as 1929, Shibata and Tsuchida reported a kinetic resolution of rac-3,4-dihydroxyphenylalanine by selective oxidation of one enantiomer using a chiral cobalt complex [Co(en)3NH3Cl]Br2 as a catalyst [46,47]. Figure 12 shows a highly enantioselective addition of diisopropy-Izinc to 2-(ferf-butylethynyl)pyrimidine-5-carbaldehyde via an autocatalytic process in the presence of a chiral octahedral cobalt complex with ethylenedi-... 

These schemes have been frequently suggested [105-107] as possible mechanisms to achieve the chirally pure starting point for prebiotic molecular evolution toward our present homochiral biopolymers. Demonstrably successftd amplification mechanisms are the spontaneous resolution of enantiomeric mixtures under race-mizing conditions, [509 lattice-controlled solid-state asymmetric reactions, [108] and other autocatalytic processes. [103, 104] Other experimentally successful mechanisms that have been proposed for chirality amplification are those involving kinetic resolutions [109] enantioselective occlusions of enantiomers on opposite crystal faces, [110] and lyotropic liquid crystals. [Ill] These systems are interesting in themselves but are not of direct prebiotic relevance because of their limited scope and the specialized experimental conditions needed for their implementation. 

A reaction process in which the product directly increases the rate of the chemical reaction is called autocatalysis. In the present case, the reaction product plays the role of a catalyst and of a potent chiral auxiliary at the same time. Hence Soai s discovery described the first example of a chirally autocatalytic reaction in organic chemistry in which the chiral product and the chiral catalyst are identical. 

Abstract Theoretical models and rate equations relevant to the Soai reaction are reviewed. It is found that in production of chiral molecules from an achiral substrate autocatalytic processes can induce either enantiomeric excess (ee) amplification or chiral symmetry breaking. The former means that the final ee value is larger than the initial value but is dependent upon it, whereas the latter means the selection of a unique value of the final ee, independent of the initial value. The ee amplification takes place in an irreversible reaction such that all the substrate molecules are converted to chiral products and the reaction comes to a halt. Chiral symmetry breaking is possible when recycling processes are incorporated. Reactions become reversible and the system relaxes slowly to a unique final state. The difference between the two behaviors is apparent in the flow diagram in the phase space of chiral molecule concentrations. The ee amplification takes place when the flow terminates on a line of fixed points (or a fixed line), whereas symmetry breaking corresponds to the dissolution of the fixed line accompanied by the appearance of fixed points. The relevance of the Soai reaction to the homochirality in life is also discussed. 

These higher order autocatalytic processes may actually be brought about by the dimer catalysts [19], but we confine ourselves to the simplest description (Eqs. 4 and 5) in terms of only monomers R and S in this section. Consideration of dimers is postponed in the following sections. The reaction Eq. 4 alone can give rise to the amplification of chirality as will be discussed. One... 

When chiral molecules are produced only spontaneously and the system has no autocatalytic processes (ko > 0, k =k2 = 0), the trajectory in the r - s phase space is obtained ... 

There is a theoretical study on the asymptotic shape of probability distribution for nonautocatalytic and linearly autocatalytic systems with a specific initial condition of no chiral enantiomers [35,36]. Even though no ee amplification is expected in these cases, the probability distribution with a linear autocatalysis has symmetric double peaks at 0 = 1 when ko is far smaller than k -,kototal number of all reactive chemical species, A, R, and S. This can be explained by the single-mother scenario for the realization of homo chirality, as follows From a completely achiral state, one of the chiral molecules, say R, is produced spontaneously and randomly after an average time l/2koN. Then, the second R is produced by the autocatalytic process, whereas for the production of the first S molecule the... 

The above examples demonstrate that mirror symmetry breaking by self-assembly of non-chiral molecules into chiral architectures is indeed a feasible process. However, in order to preserve the handedness and amplify the stochastically-generated chirality, it is imperative to couple such chance events with efficient sequential autocatalytic processes. We refer now to several experimental systems that illustrate the occurrence of such scenarios. We shall allude in particular to systems undergoing amplification via non-linear asymmetric catalysis processes, via the formation of 2-D and 3-D crystalline systems and amplification of homochiral bio-like polymers in general and oligopeptides in particular. 

As the mechanism of the reaction and possible intermediates in solution are still unknown, the phenomenon described here cannot yet be used for the targeted development of further reactions. It is, nevertheless, clear that complex formation with the organo-metallic reagents is essential to autocatalysis with asymmetric amplification. For this reason a deeper understanding of the behavior of chiral compounds during the formation of complexes would be very useful for the design and discovery of new autocatalytic processes. 

This chapter summarizes data about the application of chiral metal catalysts supported on optically active quartz crystals in hydrogenation and other reactions. Despite the low enantioselective efficiency of these catalysts, recent result show that almost 100% enantioselectivity results when they are involved in autocatalytic processes. 

Thiemann showed that this calculation of PVED for quartz crystal seems to lack a soimd physical basis because in all examined quartz locations the amoimts of d- and /-quartz crystals are equal. Hence the quartz crystals are erroneously considered as a possible source of one handedness in nature, although local formation of optically active molecules, for example, via autocatalytic processes, appears quite possible in revealing chirality rather than homochirality (Klabunovskii ). 

However, do we even need an excess A perfect example of an autocatalytic process that produces chiral substances is the formation of chiral crystals from saturated solutions of achiral or racemic molecules. One example is the crystallization of racemic of 1,1 - binaphthyl [14,15]. The R- +) and S-(—) enantiomers are drawn in Figure 3.2 For this system we have the additional "advantage" that when this molecule is melted or dissolved in a solution, the two rings are able to rotate around the bond that connects them so that they can fairly easily interconvert. We will designate this by the double arrow shown in the following chemical equation. 

Another achievement in recent asymmetric reaction study is the so-called chiral autocatalysis—where the product itself catalyzes its own asymmetric synthesis. In this process, the chiral catalyst and the products are the same in an asymmetric autocatalytic reaction. The separation of chiral catalyst from the product is not required, because the product itself is the catalyst. Starting from an optically active product with very low ee, this process allows the formation of a product with high ee values.106,114... 

The point is also made [134] that the very high surface areas and the richly interconnected three-dimensional networks of these micron-sized spaces, coupled with periods of desiccation, could together have produced microenvironments rich in cat-alytically produced complex chemicals and possibly membrane-endosed vesides of bacterial size. These processes would provide the proximate concatenation of lipid vesicular precursors with the complex chemicals that would ultimately produce the autocatalytic and self-replicating chiral systems. A 2.5 km2 granite reef is estimated to contain possibly 1018 catalytic microreactors, open by diffusion to the dynamic reservoir of organic molecules. .. but protected from the dispersive effects of flow and convection [134] as well as protected from the high flux of ultraviolet radiation impinging on the early Earth. [123,137]... 

Another scenario for the origin of homochirality was suggested by Pearson [8,9] such that chance breaks the chiral symmetry. Though the mean number of right- and left-handed enantiomers are the same, there is a nonzero probability of deviation from the equal populations of both enantiomers. The probability of establishing homochirality in a macroscopic system is, of course, very small [10], but chance produces a slight majority of one type of enantiomer and asymmetric compounds when they have once arisen act as breeders, with a power of selecting their own kind of asymmetry form [8,9]. In this scenario, produced enantiomer acts as a chiral catalyst for the production of its own kind and hence this process should be autocatalytic. 

One may wonder whether recycling processes such as a linear or a nonlinear back reaction exist in relevant autocatalytic systems. So far, we are not aware of their existence, ft is, however, possible that the back reaction rates k or ji are nonzero but too exceedingly small to be detected in laboratory experiments. Concerning the problem of homo chirality in life, very small A. or // are not unimaginable, considering the geological time scale for its establishment on earth. 

When certain cyclodipeptides are used as catalysts for the enantioselective formation of cyanohydrins, an autocatalytic improvement of selectivity is observed in the presence of chiral hydrocyanation products [80]. A commercial process for the manufacture of a pyrethroid insecticide involving asymmetric addition of HCN to an aromatic aldehyde in the presence of a cyclic dipeptide has been described [80]. Besides HCN itself, acetone cyanohydrin is also used (usually in the literature referred to as the Nazarov method), which can be activated cata-lytically by certain lanthanide complexes [81]. Acetylcyanation of aldehydes is described with samarium-based catalysts in the presence of isopropenyl acetate cyclohexanone oxime acetate is hydrocyanated with acetone cyanohydrin as the HCN source in the presence of these catalytic systems [82]. 

Asymmetric autocatalysis is a reaction in which chiral product acts as a chiral catalyst for its own production. The process is an automultiplicatiOTi of chiral compotmd. Asymmetric autocatalysis has inherent advantages over usual non-autocatalytic reaction (1) high efficiency because the process involves selfreplication and (2) the amount of catalyst increases during the reaction because the product is a catalyst. In ideal cases, catalytic activity does not decrease (3) separation of product from the catalyst is not necessary because the structures of product and catalyst are the same. 

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