Various hypotheses have been proposed to explain homo-chirality of biomolecules such as L-amino acids and D-sugars in nature. Frank proposed a purely chemical and homogeneous process of spontaneous symmetry breaking, assuming homochiral dimers of reaction products working as autocatalysts[1,2]. On the other hand, chiral crystal faces of minerals have always been considered to take a part in the selection processes of chirality. Soai and his group[3] have shown that various chiral crystals, inorganic or organic, induce autocatalytic chiral amplifying reactions of 2-substituted pyrimidine-5-carbaldehydes with diisopropyl zinc in non-polar solvents, leading to formation of corresponding pyrimidyl alkanols(structure in Figure 2) of chosen chirality in very high enantiomeric excess (Soai reaction). The combination of chiral-selective adsorption, a heterogeneous process, and autocatalysis, a homogeneous process, will make a good model to explain the mechanism of homochirality.

   In order to study the selection mechanism of chirality at crystal surfaces, adsorption structures of the chiral product molecules of Soai reaction were observed with atomic force microscopy(AFM) at chiral (10-10) faces of P- and M-crystals of α-HgS(cinnabar), (100) faces of d- and l-crystals of NaClO₃, and (100) faces of (+)- and (-)-crystals of hippuric acid (C₆H₅C(O)NHCH₂-COOH). It should be reminded here that 2₁-screw axes penetrate these surfaces. Each chiral crystal leads to selective formation of (R)- or (S)-alkanol in the actual reaction processes[3].

Although atom-resolved AFM images were observed for the bare crystal surfaces before adsorption, chirality cannot be determined with the AFM images. Single crystal X-ray diffraction, optical rotation and circular dichroism were used to determine the chirality of HgS, NaClO₃ and hippuric acid crystals, respectively.

Each crystal face was soaked in 10mM toluene solution of the alkanol of chosen chirality for 3-12 hours. The AFM images of adsorption structures were observed in air after taking the samples out of the solutions. Although well-ordered 2D-adsorption structures were observed with AFM, no difference was clearly recognized with the chirality in the first layer.

After prolonged adsorption, however, marked differences occurred depending upon the combinations of the chiralities of the adsorbates and the substrates. The AFM images in Figure 1 show that (R)-alkanol molecules adsorbed at P-HgS, l-NaClO₃ and (-)-hippuric acid crystals form micro-crystals in regular shapes. On the other hand, (S)-alkanol molecules do not form such crystals on the same substrates. The combinations leading to the micro-crystal formation induce amplification of the same chirality in the Soai reactions. The micro-crystal formation is closely related to the autocatalysis. The chiral crystal faces may be supplying dimers or oligomers of the product molecules, in Zn-alkoxide forms, of chosen chirality, which work as the autocatalyst in the solution.

A mechanism explaining the chiral-selective formation of micro-crystals at (100) face of hippuric acid is proposed in Figure 2. With the alkanol molecule, one of the N-atom in the pyrimidine ring and the –OH group will participate in H-bonding with the –OH and carbonyl groups of the substrate as shown on the right-hand side of the figure in non-polar solvents. Depending upon the distribution of binding sites at the substrate, the chiral alkanol molecules adsorb at the surface in a slanted geometry as shown in the figure. If the substrate of different chirality was used, the molecules will adsorb in geometry slanted in the opposite way. The chiralities of the substrates determine the slant direction of the first adsorption layer.

Figure 1. AFM height images of micro-crystals of (R)-pyrimidyl alkanol formed by adsorption at chiral (a):P-αHgS(10-10), (b):l-NaClO3(100) and (c):(100) face of (-)-crystal of hippuric acid.

Figure 2. Adsorption structure proposed for (S)-2-substituted pyrimidyl 5-alkanol at (100) surface of (+)-crystal of hippuric acid. Binding sites are encircled.

On the other hand, the chiralities of the adsorbed molecules determine whether stable second-layer adsorption is possible or not. A pair of (S)-alkanol molecules adsorbed at (+)-crystal face of hippuric acid are shown in Figure 2. The separation of 912 pm between the two molecules is fairly close to the corresponding distance of b’=829 pm in the bulk crystal structure of the (S)-alkanol (orthorhombic P2₁2₁2₁). Adsorption geometry of the second layer should be considered in reference to the bulk structure. The same H-bonding sites of the alkanol molecule will be used in the adsorption of the second layer. Accordingly, on the pair of adsorbed (S)-alkanol molecules in Figure 2, another (S)-alkanol molecule, 180 degrees rotated, will adsorb, avoiding steric hindrance by the bulky isopropyl group, and make a structure resembling the bulk (S)- crystal. If (R)-alkanol molecules made the first layer on the same substrate, however, the second layer adsorption is impossible. Only (S)-homochiral oligomers and micro-crystals will be formed on the (+)-crystal face. On the other hand, (R)-homochiral oligomers and micro-crystals will be formed only on the (-)-crystal face. This explains why the micro-crystal structure as in Figure 1(c) was made only with the right combinations of chiralities of the substrate and the adsorbate.

In the cases of using α-HgS and NaClO₃ as substrates, binding sites will be Hg atoms, and Na and Cl atoms, respectively, all bearing positive charges. In these cases, too, the 2₁-symmetry allows two slanted geometries of adsorption of the chiral alkanol molecules, enabling selection of homochiral 3D adsorption structures. In the actual reaction conditions, clusters of the product molecules of selected chirality, in Zn alkoxide form, coming off the crystal face will be working as the autocatalyst. 

Acknowlegement

This work was supported by JSPS KAKENHI 20225002, 20510097, 24510144, and The Institute of Science and Engineering, Chuo University.　　　

References 

[1] F. C. Frank, Biochim. Biophys. Acta, 11 (1953) 459.

[2] J. M. Brown, I. Gridnev, J. Klankermayer, Asymmetric Autocatalysis with Organozinc  Complexes; Elucidation of the Reaction Pathway, in: K. Soai ed., Amplification of Chirality, Springer,, Berlin Heidelberg, 2008, pp.35-65.

[3] K. Soai, T. Kawasaki, Asymmetric Autocatalysis with Amplification of Chirality, in: K. Soai  ed., Amplification of Chirality, Springer,, Berlin Heidelberg, 2008, pp.1-33.

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