Zhang Qi, Screen Martin A, Bowen Leon, Xu Yisheng, Zhang Xiangyang, Steed Jonathan W
State Key Laboratory of Chemical Engineering, East China University of Science and Technology Shanghai 200237 China
Department of Chemistry, Durham University Durham DH1 3LE UK.
Chem Sci. 2025 Mar 24;16(17):7459-7466. doi: 10.1039/d4sc08087d. eCollection 2025 Apr 30.
A graphene-based supramolecular gel was designed and prepared to control the crystallization process and polymorphism of pharmaceuticals. The gelators were modified at the end segments with pyrene moieties, which spontaneously interact with the graphene surface by aromatic stacking interaction resulting in a graphene-incorporated supramolecular gel linked by noncovalent interactions between urea groups. When graphene was included into the gel, the critical gel concentration and system rigidity changed significantly, fluorescence spectroscopy determined the close π-π stacking interaction between the gelator and graphene, and the material was confirmed as a true nanocomposite gel system by electron microscopy. Further the graphene was oxidatively modified to obtain hydroxylated graphene (Gr-OH), which was successfully incorporated into the gel system to serve as a medium for pharmaceutical crystallization. Glycine (GLY), caffeine (CAF) and aripiprazole (APZ) were selected as model drugs for gel surface crystallization and gel phase crystallization by Gr-OH hybrid gels. Incorporation of Gr-OH in the gel allowed close interaction by hydrogen bonding with drug molecules, resulting in different polymorphs of GLY, CAF and APZ compared to solution crystallization and shorter induction time of CAF compared to the native gel.
设计并制备了一种基于石墨烯的超分子凝胶，以控制药物的结晶过程和多晶型。凝胶因子在末端片段用芘基团进行修饰，芘基团通过芳香堆积相互作用与石墨烯表面自发相互作用，从而形成一种通过脲基之间的非共价相互作用连接的含石墨烯超分子凝胶。当石墨烯被纳入凝胶中时，临界凝胶浓度和体系刚性发生显著变化，荧光光谱法确定了凝胶因子与石墨烯之间紧密的π-π堆积相互作用，并且通过电子显微镜证实该材料为真正的纳米复合凝胶体系。进一步对石墨烯进行氧化修饰以获得羟基化石墨烯（Gr-OH），其成功地被纳入凝胶体系中，用作药物结晶的介质。选择甘氨酸（GLY）、咖啡因（CAF）和阿立哌唑（APZ）作为通过Gr-OH混合凝胶进行凝胶表面结晶和凝胶相结晶的模型药物。在凝胶中加入Gr-OH可通过与药物分子形成氢键实现紧密相互作用，与溶液结晶相比，导致GLY、CAF和APZ产生不同的多晶型，并且与天然凝胶相比，CAF的诱导时间更短。
