Studies on the development and generalization of the preparative method of organic crystals with a specific crystal structure by controlling the mode of polymorphic transition

通过这项研究，我们建立了以下方法：(1)澄清有机化合物在过饱和溶液中的超分子结构；(2)从过饱和溶液中分离出动力学形成的亚稳态晶体并阐明其晶体结构；(3)阐明从过饱和溶液中结晶过程中亚稳态多晶型向稳定多晶型转变的机制。通过这些方法的应用，我们已经阐明了优先浓缩这一我们发现的不寻常的对映体拆分现象是一个复杂系统的事件，容易导致对称性破坏。也就是说，(1)分子成核聚集体或亚稳晶相被视为混沌态，(2)混沌态之间的相变导致复杂系统的对称性破缺特征，(3)溶液中出现额外的增加返回现象。鉴于复杂体系中的相变受外部效应的控制，我们研究了优先浓缩的控制问题。因此，我们通过控制晶种晶型转变的方式，成功地诱导和抑制了择优富集。这一结果为我们提出的优惠浓缩机制提供了额外的支持。此外，我们首次成功地在种子晶体表面诱导了多态转变，并将这种现象称为外延转变。此外，我们还发现了一种新的多态转变模式，可以诱导优先富集。这一结果表明，在诱导优先富集的多态转变中存在机制上的灵活性。因此，通过仔细选择动力学结晶条件或用适当的晶体播种，优先浓缩可能适用于某些外消旋化合物。

By this research, we have established the methodologies (1) to clarify the supramolecular structure in the supersaturated solution of an organic compound, (2) to isolate the metastable crystals formed kinetically from the supersaturated solution and elucidate the crystal structure, and (3) to elucidate the mechanism of polymorphic transition of the metastable polymorphic form into the stable polymorphic form during crystallization from the supersaturated solution.By using these methodologies, it has been clarified that Preferential Enrichment, an unusual enantiomeric resolution phenomenon which we found, is an event of a complexity system which can easily lead to the symmetry breaking. Namely, (1) a molecular prenucleation aggregate or a metastable crystalline phase is regarded as an chaos state, (2) the phase transition between the chaos states induces symmetry breaking characteristic of a complexity system, and (3) additional increasing returns phenomenon occurs in solution. Since it is known that the phase transition in a complexity system is controlled by external effects, we have investigated the control of Preferential Enrichment. As a result, we have succeeded in the induction and inhibition of Preferential Enrichment by controlling the mode of polymorphic transition with seed crystals. This result lends additional support to our proposed mechanism of Preferential Enrichment. Furthermore, for the first time, we have successfully induced polymorphic transition on the surface of a seed crystal and have referred to this phenomenon as Epitaxial Transition.Furthermore, we have found a new mode of polymorphic transition that can induce Preferential Enrichment. This result indicates the mechanistic flexibility in the polymorphic transition inducing Preferential Enrichment. Therefore, by carefully choosing the kinetic crystallization conditions or seeding with appropriate crystals, Preferential Enrichment may be applicable to certain racemic compounds.