Unmasking a third polymorph of a benchmark crystal-structure-prediction compound.
Unmasking a third polymorph of a benchmark crystal-structure-prediction compound.
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DOI：
10.1002/anie.200903285
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发表时间：
2009
影响因子：
16.6
通讯作者：
Matzger, Adam J.
中科院分区：
文献类型：
--
作者：
Roy, Saikat;Matzger, Adam J.
关键词：
一种化学物质采用一种以上晶体结构的能力被称为多晶性[1]，这一现象既有好处，也有问题。[2]偶然发现新的形式通常起着关键作用，因为没有一种通用的方法来产生给定化合物的新形式。因此，了解多晶性的起源并控制结晶过程的结果以避免不需要的形式是当前的目标。[3]一个密切相关的挑战是根据给定的化学结构预测晶体结构。这个过程包括产生许多假设的多晶型并对其进行能量排序，被称为晶体结构预测(CSP)。[4]剑桥晶体数据中心(CCDC)进行的“盲测”已经认识到CSP的重要性。然而，即使是普通空间群中的简单刚性分子也是一个相当大的挑战，[5，6]由于需要探索的参数空间大得多，预测柔性分子的晶体结构更加困难。[7，8]考察结晶过程中的动力学和热力学问题可以深入了解成核机制，并有助于开发更好的CSP方法。本着这种精神，我们进行了6-氨基-2-苯磺酰亚氨基-1，2-二氢吡啶的研究(1，方案1)，这是2001年CCDC第二次盲测(分子VI)[5b]的一部分，并在比赛结束后进行了额外的审查。[9]二氢吡啶1的预测工作以失望告终，因为盲测的参与者都无法正确预测晶体结构。[5B]进一步研究[9，10]得到了分子1的第二种多晶型，声称是热力学形式；形式II包含二聚体氢键四点合成子A(方案2)。有人提出，因为形式I包含两点合子B，所以它促进了一维生长，并且这种多晶型是动力学上最受欢迎的形式。这一基本原理很好地解释了为什么在大多数CSP方法中采用的多晶型稳定性的热力学预测无法找到这种形式，并暗示了导致不稳定形式的初始结晶条件。
The ability of a chemical substance to adopt more than one crystal structure is known as polymorphism,[1] a phenomenon which can be both beneficial and problematic.[2] Serendipity often plays a key role in the discovery of new forms, because no general methodology exists for producing new forms of a given compound. Understanding the origin of polymorphism and controlling the outcome of crystallization processes to avoid undesired forms is therefore a current goal.[3] A closely related challenge is the prediction of a crystal structure from a given chemical structure. This process, which involves generating and energetically ranking many hypothetical polymorphs, is referred to as crystal-structure prediction (CSP).[4] The importance of CSP has been recognized through the “blind tests” conducted by the Cambridge Crystallographic Data Center (CCDC). However, even simple rigid molecules in common space groups present a considerable challenge,[5, 6] and prediction of flexible molecule crystal structures is even more difficult owing to the much larger parameter space to be explored.[7, 8] Examination of kinetic and thermodynamic issues in crystallization can provide insight into the mechanism of nucleation and aid development of better methodologies for CSP. In this spirit, we undertook the study of 6-amino-2-phenylsulfonylimino-1, 2-dihydropyridine (1, Scheme 1), which was part of the second CCDC blind test in 2001 (molecule VI)[5b] and then subjected to additional scrutiny after the contest.[9]The dihydropyridine 1 prediction exercise ended with disappointment, as none of the participants of the blind test were able to predict the crystal structure correctly.[5b] Further study [9, 10] yielded a second polymorph of molecule 1, claimed to be the thermodynamic form; form II contained dimer hydrogen-bonding four-point synthon A (Scheme 2). It was proposed [9] that because form I contains two-point synthon B, it facilitates 1D growth and that this polymorph was the kinetically favored form. This rationale neatly explained why thermodynamic predictions of polymorph stability employed in most CSP approaches failed to find this form and implicated the initial crystallization conditions in leading to an unstable form.
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影响因子：
15
作者：
Price, CP;Grzesiak, AL;Matzger, AJ
通讯作者：
Matzger, AJ
DOI：
10.1107/s0108768100004584
发表时间：
2000-08-01
影响因子：
1.9
作者：
Lommerse, JPM;Motherwell, WDS;Williams, DE
通讯作者：
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影响因子：
3.1
作者：
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通讯作者：
Jayatilaka, Dylan
DOI：
10.1107/s0108768109004066
发表时间：
2009-04-01
影响因子：
1.9
作者：
Day, Graeme M.;Cooper, Timothy G.;Schweizer, Bernd
通讯作者：
Schweizer, Bernd
影响因子：
3.8
作者：
Roy, Saikat;Nangia, Ashwini
通讯作者：
Nangia, Ashwini