Crystal engineering of the composition of pharmaceutical phases. 3. Primary amide supramolecular heterosynthons and their role in the design of pharmaceutical co-crystals

被引:129
作者
McMahon, JA [1 ]
Bis, JA [1 ]
Vishweshwar, P [1 ]
Shattock, TR [1 ]
McLaughlin, OL [1 ]
Zaworotko, MJ [1 ]
机构
[1] Univ S Florida, Dept Chem, Tampa, FL 33620 USA
来源
ZEITSCHRIFT FUR KRISTALLOGRAPHIE | 2005年 / 220卷 / 04期
关键词
crystal engineering; co-crystal; pharmaceutical co-crystal; pharmaceutical phases; hydrogen bond; supramolecular synthesis;
D O I
10.1524/zkri.220.4.340.61624
中图分类号
O7 [晶体学];
学科分类号
0702 ; 070205 ; 0703 ; 080501 ;
摘要
A Cambridge Structural Database study of supramolecular synthons involving primary amides reveals that 84% form amide-amide dimers, whereas 14% form catemers in the absence of other competing hydrogen bond donors and/or acceptors. However in the presence of chemically different but complementary functional groups, e.g., carboxylic acids or aromatic nitrogen moieties, primary amides tend to form supramolecular heterosynthons. Supramolecular heterosynthons represent an opportunity for design of multi-component crystals (co-crystals) in which one molecule contains a primary amide and a second molecule (the co-crystal former) contains the functional group that is complementary to the primary amide. The results of the CSD analysis facilitated the selection of components for seven new primary amide co-crystals: A. Isonicotinamide/2-hydroxybenzoic acid (1: 1); B. Nicotinamide/3-hydroxybenzoic acid (1: 1); C. Pyrazinamide/2,5dihydroxybenzoic acid (1: 1); D. Carbamazepine (CBZ)/ 4,4'-bipyridine (2: 1); E. CBZ/4-arrrinobenzoic acid (2: 1); E CBZ/4-aminobenzoic acid/H2O (2: 1: 1); G. CBZ/2,6-pyridinedicarboxylic acid (1: 1). The molecular recognition events involving the amide moieties are discussed in the context of our experimental results and their implications for crystal engineering of pharmaceutical co-crystals.
引用
收藏
页码:340 / 350
页数:11
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