Price Sarah Sally L
Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK.
Acc Chem Res. 2009 Jan 20;42(1):117-26. doi: 10.1021/ar800147t.
The phenomenon of polymorphism, the ability of a molecule to adopt more than one crystal structure, is a well-established property of crystalline solids. The possible variations in physical properties between polymorphs make the reliable reproduction of a crystalline form essential for all research using organic materials, as well as quality control in manufacture. Thus, the last two decades have seen both an increase in interest in polymorphism and the availability of the computer power needed to make the computational prediction of organic crystal structures a practical possibility. In the past decade, researchers have made considerable improvements in the theoretical basis for calculating the sets of structures that are within the energy range of possible polymorphism, called crystal energy landscapes. It is common to find that a molecule has a wide variety of ways of packing with lattice energy within a few kilojoules per mole of the most stable structure. However, as we develop methods to search for and characterize "all" solid forms, it is also now usual for polymorphs and solvates to be found. Thus, the computed crystal energy landscape reflects and to an increasing extent "predicts" the emerging complexity of the solid state observed for many organic molecules. This Account will discuss the ways in which the calculation of the crystal energy landscape of a molecule can be used as a complementary technique to solid form screening for polymorphs. Current methods can predict the known crystal structure, even under "blind test" conditions, but such successes are generally restricted to those structures that are the most stable over a wide range of thermodynamic conditions. The other low-energy structures can be alternative polymorphs, which have sometimes been found in later experimental studies. Examining the computed structures reveals the various compromises between close packing, hydrogen bonding, and pi-pi stacking that can result in energetically feasible structures. Indeed, we have observed that systems with many almost equi-energetic structures that contain a common interchangeable motif correlate with a tendency to disorder and problems with control of the crystallization product. Thus, contrasting the computed crystal energy landscape with the known crystal structures of a given molecule provides a valuable complement to solid form screening, and the examination of the low-energy structures often leads to a rationalization of the forms found.
多晶型现象，即分子具有不止一种晶体结构的能力，是晶体固体已确定的一种特性。多晶型物之间物理性质的可能差异使得对于所有使用有机材料的研究以及制造过程中的质量控制而言，可靠地重现晶体形式至关重要。因此，在过去二十年中，人们对多晶型现象的兴趣有所增加，同时也具备了使有机晶体结构的计算预测成为实际可能所需的计算机能力。在过去十年中，研究人员在计算可能的多晶型能量范围内的结构集（即晶体能量景观）的理论基础方面取得了相当大的进展。通常会发现，一个分子具有多种堆积方式，其晶格能量与最稳定结构相比每摩尔相差几千焦耳。然而，随着我们开发搜索和表征“所有”固体形式的方法，现在发现多晶型物和溶剂化物也很常见。因此，计算得到的晶体能量景观反映并在越来越大的程度上“预测”了许多有机分子所观察到的固态的新出现的复杂性。本综述将讨论计算分子晶体能量景观的方法如何用作多晶型物固体形式筛选的补充技术。目前的方法可以预测已知的晶体结构，即使在“盲测”条件下也是如此，但这种成功通常仅限于在广泛的热力学条件下最稳定的那些结构。其他低能量结构可能是替代多晶型物，有时会在后来的实验研究中发现。检查计算得到的结构揭示了在紧密堆积、氢键和π-π堆积之间的各种折衷，这些折衷可能导致能量上可行的结构。实际上，我们已经观察到，具有许多几乎等能量结构且包含共同可互换基序的系统与无序倾向以及结晶产物控制方面的问题相关。因此，将计算得到的晶体能量景观与给定分子的已知晶体结构进行对比，为固体形式筛选提供了有价值的补充，并且对低能量结构的研究通常会导致对所发现形式的合理化解释。
