Zhang Si-Wei, Kendrick John, Leusen Frank J J, Yu Lian
School of Pharmacy and Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53705.
School of Life Sciences, University of Bradford, Bradford BD7 1DP, UK.
J Pharm Sci. 2014 Sep;103(9):2896-2903. doi: 10.1002/jps.23929. Epub 2014 Mar 14.
A dispersion-corrected density functional theory method has been used to study the formation energies and volumes of cocrystals. For four cocrystals of nicotinamide (NIC) and (R)-mandelic acid, a broad agreement is found between experimental and computed values. We report that cocrystals containing NIC are anomalous as their formation generally decreases energy but expands volume. In this respect, the formation of NIC cocrystals is in contrast to most physical processes, but similar to water freezing. As in the case of water freezing, the cocrystallization with NIC leads to stronger hydrogen bonds and looser molecular packing, a combination that is likely responsible for the anticorrelation between energy and volume. NIC has two conformers 4 kJ/mol apart in energy and both can form cocrystals, with the resulting structures having comparable formation energies and volumes. These results are relevant for understanding the nature of cocrystallization and why NIC is a prolific cocrystal former.
一种色散校正的密度泛函理论方法已被用于研究共晶体的形成能和体积。对于烟酰胺（NIC）和（R）-扁桃酸的四种共晶体，实验值和计算值之间存在广泛的一致性。我们报告称，含NIC的共晶体是反常的，因为它们的形成通常会降低能量但增加体积。在这方面，NIC共晶体的形成与大多数物理过程相反，但与水结冰相似。就像水结冰的情况一样，与NIC共结晶会导致更强的氢键和更松散的分子堆积，这种组合可能是能量和体积反相关的原因。NIC有两个能量相差4 kJ/mol的构象异构体，两者都能形成共晶体，所得结构具有相当的形成能和体积。这些结果对于理解共结晶的本质以及为什么NIC是一种多产的共晶体形成物具有重要意义。
