Do polymorphic compounds make good cocrystallizing agents?: A structural case study that demonstrates the importance of synthon flexibility
Do polymorphic compounds make good cocrystallizing agents?: A structural case study that demonstrates the importance of synthon flexibility
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DOI：
10.1021/cg025593z
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发表时间：
2003-03-01
影响因子：
3.8
通讯作者：
Nieuwenhuyzen, M
中科院分区：
文献类型：
--
作者：
Aakeröy, CB;Beatty, AM;Nieuwenhuyzen, M
四种多态化合物异烟酰胺(1)、2-氨基-3-硝基吡啶(2)、4-氯苯酰胺(3)和马来酰肼(4)形成分子共晶的能力已在系统结构研究中进行了研究。化合物1-3参与多种二元和三元共晶（在1的情况下），芳香族或脂肪族化合物被大量官能团取代。然而，尽管付出了相当大的努力，仍不可能与4形成任何共晶。其原因可能是，尽管已知的4有三种多态性，但它们都含有相同的氢键合子。相比之下，1-3的多晶型表现出相当大的合成灵活性，例如，同一化合物的多晶型中存在不同的氢键相互作用。因为1-3可以通过多种方式形成强大的合子，而4总是参与相同的初级氢键相互作用，这可以解释为什么前者化合物很容易在同一晶格内容纳其他分子，而没有已知的4的共晶。
The ability of four polymorphic compounds, isonicotinamide (1), 2-amino-3-nitropyridine (2), 4-chlorobenzamide (3), and maleic hydrazide (4), to form molecular cocrystals has been examined in a systematic structural study. Compounds 1-3 participate in a wide variety of binary and ternary (in the case of 1) cocrystals with aromatic or aliphatic compounds substituted with a multitude of functional groups. However, despite considerable efforts, it has not been possible to form any cocrystals with 4. The reason for this may be due to the fact that even though there are three known polymorphs of 4, they all contain the same hydrogen-bonding synthons. In contrast, the polymorphs of 1-3 display considerable synthon flexibility, e.g., different hydrogen bond interactions are present in polymorphs of the same compound. Because 1-3 can form robust synthons in a variety of ways, whereas 4 always engages in the same primary hydrogen bond interactions, it may explain why the former compounds are readily able to accommodate other molecules within the same lattice whereas there are no known cocrystals of 4.