School of Pharmacy and Department of Chemistry, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin 53705, USA.
Acc Chem Res. 2010 Sep 21;43(9):1257-66. doi: 10.1021/ar100040r.
Diamond and graphite are polymorphs of each other: they have the same composition but different structures and properties. Many other substances exhibit polymorphism: inorganic and organic, natural and manmade. Polymorphs are encountered in studies of crystallization, phase transition, materials synthesis, and biomineralization and in the manufacture of specialty chemicals. Polymorphs can provide valuable insights into crystal packing and structure-property relationships. 5-Methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile, known as ROY for its red, orange, and yellow crystals, has seven polymorphs with solved structures, the largest number in the Cambridge Structural Database. First synthesized by medicinal chemists, ROY has attracted attention from solid-state chemists because it demonstrates the remarkable diversity possible in organic solids. Many structures of ROY polymorphs and their thermodynamic properties are known, making ROY an important model system for testing computational models. Though not the most polymorphic substance on record, ROY is extraordinary in that many of its polymorphs can crystallize simultaneously from the same liquid and are kinetically stable under the same conditions. Studies of ROY polymorphs have revealed a new crystallization mechanism that invalidates the common view that nucleation defines the polymorph of crystallization. A slow-nucleating polymorph can still dominate the product if it grows rapidly and nucleates on another polymorph. Studies of ROY have also helped understand a new, surprisingly fast mode of crystal growth in organic liquids cooled to the glass transition temperature. This growth mode exists only for those polymorphs that have more isotropic, and perhaps more liquid-like, packing. The rich polymorphism of ROY results from a combination of favorable thermodynamics and kinetics. Not only must there be many polymorphs of comparable energies or free energies, many polymorphs must be kinetically stable and crystallize at comparable rates to be observed. This system demonstrates the unique insights that polymorphism provides into solid-state structures and properties, as well as the inadequacy of our current understanding of the phenomenon. Despite many studies of ROY, it is still impossible to predict the next molecule that is equally or more polymorphic. ROY is a lucky gift from medicinal chemists.
它们的组成相同，但结构和性质不同。许多其他物质也表现出多态性：无机和有机、天然和人工合成。多晶型体在结晶学、相变、材料合成和生物矿化以及特种化学品制造的研究中都会遇到。多晶型体可以提供对晶体堆积和结构-性质关系的有价值的见解。5-甲基-2-[(2-硝基苯基)氨基]-3-噻吩甲腈，因其红色、橙色和黄色晶体而被称为 ROY，它有七种已确定结构的多晶型体，是剑桥结构数据库中最多的。ROY 最初是由药物化学家合成的，因其在有机固体中表现出显著的多样性而引起了固态化学家的关注。ROY 许多多晶型体的结构和热力学性质已经为人所知，使其成为测试计算模型的重要模型体系。尽管 ROY 不是记录中最具多晶型性的物质，但它非常特别，因为它的许多多晶型体可以同时从同一种液体中结晶，并且在相同条件下是动力学稳定的。ROY 多晶型体的研究揭示了一种新的结晶机制，该机制否定了结晶的成核决定多晶型体的常见观点。如果一种缓慢成核的多晶型体生长迅速，并在另一种多晶型体上成核，它仍然可以主导产物。ROY 的研究还帮助人们了解了一种在有机液体冷却到玻璃化转变温度时出现的新的、非常快速的晶体生长模式。这种生长模式仅存在于那些具有更各向同性、也许更具液态特征的包装的多晶型体中。ROY 的丰富多态性源于热力学和动力学的综合作用。不仅要有许多能量或自由能相当的多晶型体，而且许多多晶型体必须是动力学稳定的，并以可比的速率结晶才能被观察到。该系统展示了多晶型性为固态结构和性质提供的独特见解，以及我们目前对该现象的理解的不足。尽管对 ROY 进行了许多研究，但仍然不可能预测下一个同样或更具多晶型性的分子。ROY 是药物化学家的幸运礼物。
