Racemic Naproxen: A Multidisciplinary Structural and Thermodynamic Comparison with the Enantiopure Form
Racemic Naproxen: A Multidisciplinary Structural and Thermodynamic Comparison with the Enantiopure Form
复制标题
DOI：
10.1021/cg201203u
复制
发表时间：
2011-12-01
影响因子：
3.8
通讯作者：
Price, Sarah L.
中科院分区：
文献类型：
--
作者：
Braun, Doris E.;Ardid-Candel, Miguel;Price, Sarah L.
根据计算预测 (RS)-萘普生比治疗上使用的和更多研究的纯手性 (S)-萘普生更稳定，我们进行了一项跨学科研究来对比这两种化合物。从粉末 X 射线衍射数据 (Pbca) 解出了外消旋化合物的晶体结构，并且显示出与纯手性结构 (P2(1)) 没有堆积相似性。构建二元熔点相图以确认外消旋物质的性质，并使用差示扫描量热和溶解度测量来估计晶体之间的焓差（Delta H-R+S -> RS(cry)），在 T 温度下为 1.5 +/- 0.3 kJ.mol(-1)，类似于 156 摄氏度，在 T 温度下为 -2.4 +/- 1.0 kJ.mol(-1)。 范围为 10-40 摄氏度。对估计 AHR,s ksaY 所涉及的不同近似值的比较表明，晶格能量的差异高估了 (RS) 晶体的稳定性。萘普生晶格能量景观证实，所有实际重要的晶体结构均已被发现和表征，并为外消旋形式的晶体生长问题提供了见解。这凸显了计算模型在研究手性结晶方面的互补性。
Following the computational prediction that (RS)-naproxen would be more stable than the therapeutically used and more studied homochiral (S)-naproxen, we performed an interdisciplinary study contrasting the two compounds. The crystal structure of the racemic compound was solved from powder X-ray diffraction data (Pbca) and showed no packing similarity with the homochiral structure (P2(1)). The binary melting point phase diagram was constructed to confirm the nature of the racemic species, and differential scanning calorimetric and solubility measurements were used to estimate the enthalpy difference between the crystals (Delta H-R+S -> RS(cry)) to be 1.5 +/- 0.3 kJ.mol(-1) at T similar to 156 degrees C and -2.4 +/- 1.0 kJ.mol(-1) in the range 10-40 degrees C. A comparison of the different approximations involved in estimating AHR,s ksaY implied that the difference in the lattice energies overestimated the stability of the (RS) crystal. The naproxen lattice energy landscape confirmed that all the practically important crystal structures have been found and characterized and provided insights into the crystal growth problems of the racemic form. This highlights the complementarity of computational modeling in investigating chiral crystallization.