In this paper we have established a correlation between the conformation crossover of carbamazepine and associated polymorph transformation. This was achieved by using a combination of quantum chemical calculations and in situ IR spectroscopy for performing a conformational analysis of carbamazepine molecules in its saturated solution in scCO2 being in permanent contact with the carbamazepine solid form. Using quantum calculations, we determined two carbamazepine conformers, whose spectral signatures were then found in experimental IR spectra. Further analysis of the IR spectra allowed us to quantify the distribution of these conformations in supercritical CO2. We found that this distribution can be changed by heating from 40°C to 110°C along two isochores at 1.1 and 1.3 of the critical CO2 density. Using in situ Raman spectroscopy we proved that the appearing conformational crossover correlates with the polymorphic transformation of the carbamazepine solid form. Moreover, this transformation was proved by the results of IR diffuse reflection spectroscopy.

中文翻译：

---

卡马西平的构象交叉与其在超临界CO2中的多态转变之间的相关性：在控制多态性的途径上。

在本文中，我们建立了卡马西平的构象转换与相关的多晶型物转化之间的相关性。这是通过结合使用量子化学计算和原位红外光谱法对卡马西平分子在scCO2饱和溶液中进行的构象分析而实现的，该溶液与卡马西平固体形式保持永久接触。使用量子计算，我们确定了两个卡马西平构象异构体，然后在实验红外光谱中发现了它们的光谱特征。红外光谱的进一步分析使我们能够量化这些构象在超临界CO2中的分布。我们发现，可以通过在临界CO2密度的1.1和1.3下沿着两个等时线从40°C加热到110°C来改变这种分布。使用原位拉曼光谱，我们证明了出现的构象交叉与卡马西平固体形式的多晶型转化有关。此外，红外漫反射光谱的结果证明了这种转变。