Childs Scott L, Stahly G Patrick, Park Aeri
SSCI, Inc., an Aptuit company, 3065 Kent Avenue, West Lafayette, Indiana 47906, USA.
Mol Pharm. 2007 May-Jun;4(3):323-38. doi: 10.1021/mp0601345. Epub 2007 Apr 27.
Salts and cocrystals are multicomponent crystals that can be distinguished by the location of the proton between an acid and a base. At the salt end of the spectrum proton transfer is complete, and on the opposite end proton transfer is absent in cocrystals. However, for acid-base complexes with similar pK(a) values, the extent of proton transfer in the solid state is not predictable and a continuum exists between the two extremes. For these systems, both the DeltapK(a) value (pK(a) of base - pK(a) of acid) and the crystalline environment determine the extent of proton transfer. A total of 20 complexes containing theophylline and guest molecules with DeltapK(a) values less than 3 have been prepared, resulting in 13 cocrystals, five salts, and two complexes with mixed ionization states based on IR spectroscopy and single-crystal diffraction data. We propose modifications to the DeltapK(a) rule for selecting salt screen counterions that focus on the discovery of solid forms with useful physical properties rather than an arbitrary cutoff value for DeltapK(a).
盐和共晶体是多组分晶体，可根据质子在酸和碱之间的位置来区分。在光谱的盐端，质子转移是完全的，而在另一端，共晶体中不存在质子转移。然而，对于具有相似pK(a)值的酸碱络合物，固态下质子转移的程度是不可预测的，并且在两个极端之间存在一个连续体。对于这些体系，ΔpK(a)值（碱的pK(a) - 酸的pK(a)）和晶体环境都决定了质子转移的程度。基于红外光谱和单晶衍射数据，总共制备了20种含有茶碱和ΔpK(a)值小于3的客体分子的络合物，得到了13种共晶体、5种盐和2种具有混合电离态的络合物。我们建议对选择盐筛选抗衡离子的ΔpK(a)规则进行修改，重点是发现具有有用物理性质的固体形式，而不是对ΔpK(a)设置任意截止值。
