Chiral seeding

Chirally Seeded Cytosine Peptide Nucleic Acid... 

Some achiral organic compounds form chiral crystals, with each crystal exhibiting one of two possible enantiomorphs [9-13]. These chiral crystals composed of an achiral organic compound may serve as an efficient chiral seed in a prebiotic world, therefore, a study of asymmetric autocatalysis using these chiral organic crystals is an interesting subject. 

First of all, they are kinetically inert. This means that deprotonation of the four acid groups of the pyridyl moieties would not cause the complete destruction of the chiral complexes but should leave a small amount of chiral seeds (Scheme 2, route b). In addition these species are huge built by one million porphyrins. Therefore, it is conceivable that most water is excluded from the inner part of these species giving rise to families of pK.tl values. As a result, pH changes around the pvalue will not lead to a complete disassembly a certain small amount of aggregates might resist (condition A). 

Scheme 2 Picture of the pH-induced disassembly of the chiral porphyrin aggregate and of the two possible reassembling paths. Route a the chiral aggregate is completely disassembled after the pH-jump. Route b some undetectable chiral seed survive the pH-jump. Modified from [45]...

Second, these assemblies are excellent chiral templates which very efficiently self-catalyse their enantioselective growth [47]. Therefore a lasting small amount of chiral seeds should be enough to promote the formation of the chiral supramolecu-lar complex (condition B) (Scheme 2, route b). If conditions A and B hold, route h of Scheme 2 should be prevalent over route a, permitting cycling between a static and a quasi-dynamic system. 

The concept of quasi-dynamic is fundamental to design the erase-rewrite system. It is strictly related to the possible presence of chiral seeds in solution. So we define the system quasi-dynamic because part of it should stay in a static condition (the seeds) and part in a dynamic condition (the monomers). From a spectroscopic point of view, at high pH, the ICD signal should disappear (in solution there should be achiral monomers plus a spectroscopically undetectable amount of chiral seeds) and reappear at low pH (chiral reassembly) because the chiral reassembly is driven by the seeds. 

As hypothesized, the remarkable kinetic inertia of the imprinted aggregates allows for the persistence of a spectroscopically undetectable amount of chiral seeds which drives the re-assembly of the chiral structure (Scheme 2, route b). Ten consecutive cycles were performed to test the system on-off cycling ability, but, in principle, there are no apparent limitations to the number of cycles that can be performed. 

In order to demonstrate that the chiral porphyrin reassembly is due to the presence of the (spectroscopically silent) chiral seeds of the porphyrin aggregate, various solutions of the chiral aggregates were kept at pH 9.0 (that is in the disassembled state) for different time intervals before reassembling them (lowering the pH at 2.3) [49]. In fact, if the chiral reassembly is driven by the presence of inert chiral seeds, then (at pH 9.0) there must be a time interval after which the chiral seeds will disassemble. Then chirality would not be reversible anymore and the system will reassemble in a non-chiral fashion (see route a in Scheme 2). Indeed, after about 24 h at pH 9, the CD at pH 2.3 is not restored anymore because the chiral seeds also disassembled. 

Scheme 3.3-3 Enantiomeric separation of 10a by inciusion com-piexation with 111 in the presence of chiral seed crystals.

The reaction can be initiated by a diversity of small chiral seeds including chiral crystals of achiral compounds such as quartz [175] and adenine [176]. Recently, it was found that even isotopomers are effective [177,178]. An amino acid with the level of enrichment derivable from CPL irradiation was found to be an effective seed [179], as was the CPL-irradiated reaction product itself [180], providing a model for a reaction that can be amplified from the kinds of enantiomeric imbalances found in Nature. 

Resolution of a racemic mixture was discovered by Pasteur in the last century. It remains an useful method to prepare enantiomerically pure compounds, although the yield in the desired enantiomw cannot exceed 50%. It is realized by the reaction of stoichiometric amounts of a chiral auxiliary which will produce a I I mixture of diastereomers, generally easy to separate. Removal of the chiral auxiliary graerates the desired enantiomer. A special case of resolution is one in which the racemic compound crystallizes as a conglomerate. Here, a chiral seed can propagate the production of... 

So we can generate chiral material from racemic or achiral material quite easily. It s just that we couldn t predict ahead of time which one we might get— that is, unless you have an external chiral influence We discussed this general idea when we described the chiral photodestruction of molecules in interstellar space. The chiral force here is the circularly polarized light that is expected to preferentially destroy one enantiomer more rapidly than the other. Chemists know that if you have a saturated solution that is cooling down and ready to crystallize, you can influence which crystal you get from the two racemic possibilities by "seeding" the solution with a chiral seed crystal. This will often initiate the formation of the desired enantiomeric crystal, and then the autocatalysis takes over and more of these enantiomeric crystals are formed. 

Table 4 Examples of the crystallization of 5 OEt with or without seeding and their photoreaction into the chiral dimer."...

The spectrometer is fitted with a skimmed c.w. supersonic molecular beam source. Many chiral species of interest are of low volatility, so a heated nozzle-reservoir assembly is used to generate, in a small chamber behind a 70-pm pinhole, a sample vapor pressure that is then seeded in a He carrier gas as it expands through the nozzle [103], Further details of this apparatus are given elsewhere [36, 102, 104],... 

The technique of purification based on seeded crystallization of the desired isomer and simultaneous racemisation of the undesired isomer, termed crystallization induced asymmetric transformation , has been covered by Davey (1994) with the example of a chiral pesticide, paclobutrazol (P). 

Recrystallization of 96 from benzene afforded colorless prisms. That each crystal is chiral was shown by photochemical conversion into the optically active 97. Crystals of 96 which gave (+)- and (—)-97 on photocyclization have been tentatively identified as (+)- and (—)-crystals of 96, respectively. Large amounts of the (+)- and (—)-crystals of 96 can easily be prepared by seeding with finely powdered (+)- and (—)-... 

Several secondary metabolites are dithiolanes, as for instance the allelochem-icals found in the tropical weed, Sphenoclea zeylanica. Zeylanoxide A is present in two stereoisomeric forms depending on whether the chirality at sulfur is (R) or (5) the latter form is 44 (Scheme 15). Zeylanoxides B are similar but in these cases the oxide function is on the sulfur at the 2 position. These molecules inhibited root growth in rice seedlings as well as the germination of letuce seeds.95... 

From these examples, it becomes clear that molecular symmetry can spontaneously break into chiral domains in the absence of any external force or seed. However, in every known case, the net symmetry remains intact, and the overall chirality sums to zero in the environment. Nevertheless, the spontaneous formation of macroscopic chiral regions in systems of associating achiral molecules is of interest to those who contemplate induction of molecular chirality in the context of prebiotic reaction chemistry. 

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