A concerted approach for a better understanding and control of the polymorphism of benzamide molecular crystals - synthesis as well as experimental and theoretical characterisation

这个项目的目的是增加对苯甲酰胺的多态和成核的了解，苯甲酰胺是在SPP 1415的第一个项目期间开发的。此外，我们还努力将我们的研究扩展到相关的分子体系。在第一个资助期内，我们惊讶地发现苯甲酰胺表现出很强的两亲性。这为药物及其前体等结构相似的分子开辟了有希望的途径。苯甲酸钠表现出不寻常的胶束状堆积，表明苯甲酰胺和苯甲酸钠的分子相互作用相似。在接下来的一段时间里，我们计划将我们的研究重点放在两个系统的非均相成核过程上。我们打算揭开两亲性分子在极性/非极性界面上预组织的特殊结构动机，以及Tenside的影响和从界面上的分子单分子层开始生长的核的形成。我们还计划研究形成胶束聚集体作为可能的前体的可能性，并将跟随它们的自组织进入介晶。在苯甲酸钠的情况下，实验观察到的转变发生在固体中，而且速度很慢，因此很容易进行现场分析。我们认为苯甲酸钠是研究成核和生长过程中的分级过程的理想体系。因此，我们将采用综合、理论和实验表征相结合的方法。因此，参与其中的所有三个小组的能力都是至关重要的。BREU小组需要开发合成方法，以尽可能选择性地在界面上成核。在Zahn小组中进行的原子模拟将有助于理解相关的分子相互作用，并能够提出界面上自组织的可能场景。Senker小组将为核磁共振光谱实验做出贡献，分别提供对界面和胶束分子组装的直接访问。它们也适用于验证从MD模拟中得出的结构动机。由此得出的成核现象的洞察力服务于实现对分子晶体中的多态的总体控制的长期目标。

The aim of this project is to increase the understanding of polymorphism and nucleation of benzamide, which was developed during the first project period of the SPP 1415. Additionally, we strive to extend our studies to related molecular systems. During the first funding period we found to our surprise that benzamide exhibits a strong amphiphilic character. This opens up promising avenues for structurally similar molecules like pharmaceuticals and their precursors. Sodium benzoate was shown to display an unusual micelle like packing, indicating similar molecular interactions for benzamide and sodium benzoate. For the oncoming period we plan to focus our research efforts on heterogeneous nucleation processes for both systems. We intend to unravel specific structural motives of the pre-organisation of amphiphilic molecules at polar/unpolar interfaces as well as the influence of tensides and the formation of nuclei starting to grow from molecular monolayers at the interfaces. We also plan to investigate the potential of forming micellar aggregates as possible precursor and will follow their self-organisation into mesocrystals. In the case of sodium benzoate the experimentally observed transformation occurs in the solid-state and is slow allowing for easy access with in-situ analytics. We believe sodium benzoate to be an ideal system to study the hierarchical processes during the nucleation and growth mechanism. Therefore, we will use a coordinated approach combining synthesis, theory and experimental characterisation. As such the competence of all three groups involved is essential. The Breu group need to develop synthetic methods allowing for a nucleation which occurs at the interfaces as selectively as possible. The atomistic simulations carried out in the Zahn group will help to understand the relevant molecular interactions and is able to suggest possible scenarios of the selforganisation at the interfaces. The Senker group will contribute with NMR spectroscopic experiments, providing direct access to the molecular assembly at the interfaces and the micelles, respectively. They are also suited to validate the structural motives derived from the MD simulations. The thus derived insight into the nucleation phenomenon serves the long term goal to reach a general control of polymorphism in molecular crystals.