Chimie ParisTech, PSL, 11 Rue Pierre et Marie Curie, CEDEX 05, 75231 Paris, France.
Institut Parisien de Chimie Moléculaire (IPCM)-UMR 8232, Sorbonne Université, 4 Place Jussieu, 75252 Paris, France.
Int J Mol Sci. 2023 Jul 31;24(15):12288. doi: 10.3390/ijms241512288.
We sought to determine the cyclodextrins (CDs) best suited to solubilize a patented succinimido-ferrocidiphenol (SuccFerr), a compound from the ferrociphenol family having powerful anticancer activity but low water solubility. Phase solubility experiments and computational modelling were carried out on various CDs. For the latter, several CD-SuccFerr complexes were built starting from combinations of one or two CD(s) where the methylation of CD oxygen atoms was systematically changed to end up with a database of ca. 13 k models. Modelling and phase solubility experiments seem to indicate the predominance of supramolecular assemblies of SuccFerr with two CDs and the superiority of randomly methylated β-cyclodextrins (RAMEβCDs). In addition, modelling shows that there are several competing combinations of inserted moieties of SuccFerr. Furthermore, the models show that ferrocene can contribute to high stabilization by making atypical hydrogen bonds between Fe and the hydroxyl groups of CDs (single bond with one OH or clamp with two OH of the same glucose unit).
我们试图确定最适合溶解专利的琥珀酰亚胺二茂铁二苯酚（SuccFerr）的环糊精（CDs），这是一种具有强大抗癌活性但水溶性低的二茂铁二苯酚家族化合物。在各种 CDs 上进行了相溶解度实验和计算建模。对于后者，从一个或两个 CD 的组合开始构建了几个 CD-SuccFerr 配合物，其中 CD 氧原子的甲基化被系统地改变，最终建立了大约 13 k 个模型的数据库。建模和相溶解度实验似乎表明，SuccFerr 与两个 CDs 的超分子组装占主导地位，随机甲基化的β-环糊精（RAMEβCDs）具有优越性。此外，模型表明，存在 SuccFerr 的插入部分的几个竞争组合。此外，模型表明，二茂铁可以通过在 Fe 和 CDs 的羟基之间形成非典型氢键（与一个 OH 的单键或同一葡萄糖单元的两个 OH 的夹具）来促进高稳定性。
