Ionic liquid forms of biologically active molecules (e.g., active pharmaceutical ingredients or herbicides) are often designed by using weakly interacting, conformationally flexible ions. However, crystalline forms of these molecules involve strong interactions and efficient packing. The salts of biologically active molecules may completely lack the directional supramolecular synthons typically used in crystal engineering, and thus new tools must be developed to control the crystal packing without strong directional interactions and predict their structure–property relationships in advance. The crystal structures of tetrabutylammonium and phosphonium salts of two structurally related, biologically active ions, salicylate and dicamba, show systematic differences from their free acids and metal salts, which are dominated by strong directional interactions. Molecular conformation and the structure of oligomeric ions of acids and their conjugate bases are conserved across multiple structures. The use of flexible, weakly coordinating cations to make salts of high melting biologically active acids can dramatically change melting points based on the size and shape complementarity of the ions and the ability of the cations to enhance anion–anion repulsion.

中文翻译：

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熔点趋势可以帮助我们开发新的工具来控制弱相互作用离子的晶体堆积吗？

生物活性分子（例如，活性药物成分或除草剂）的离子液体形式通常是通过使用弱相互作用的，构象柔性的离子来设计的。但是，这些分子的晶体形式涉及强相互作用和有效堆积。具有生物活性的分子的盐可能完全缺乏通常在晶体工程中使用的定向超分子合成子，因此必须开发新的工具来控制晶体堆积而无强烈的定向相互作用，并提前预测其结构与性质的关系。两种与结构相关的，具有生物活性的离子，水杨酸盐和麦草畏的四丁基铵盐和salts盐的晶体结构与它们的游离酸和金属盐显示出系统的区别，它们主要由强烈的方向性互动所主导。酸的寡聚离子及其共轭碱基的分子构象和结构在多种结构中均保守。使用柔性的，弱配位的阳离子来制备高熔点生物活性酸的盐，可以根据离子的大小和形状的互补性以及阳离子增强阴离子与阴离子之间的排斥力的能力来显着改变熔点。