Wang Wei, Gong Jianye, Zhao Jiaqiang, Zhang Hao, Wen Wei, Zhao Zujin, Li Yan Jie, Wang Jianguo, Huang Cheng Zhi, Gao Peng Fei
Key Laboratory of Biomedical Analytics, Chongqing Science and Technology Bureau, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China.
College of Chemistry and Chemical Engineering, Inner Mongolia Key Laboratory of Fine Organic Synthesis, Inner Mongolia University, Hohhot, 010021, China.
Adv Sci (Weinh). 2024 Sep;11(35):e2403249. doi: 10.1002/advs.202403249. Epub 2024 Jul 16.
Exploring the molecular packing and interaction between chiral molecules, no matter single enantiomer or racemates, is important for recognition and resolution of chiral drugs. However, sensitive and non-destructive analysis methods are lacking. Herein, an intermolecular-charge transfer (ICT) based spectroscopy is reported to reveal the differences in interaction between the achiral acceptor 1,2,4,5-tetracyanobenzene (TCNB) and the chiral donors, including S, R, and racemic naproxen (S/R/rac-NAP). In this process, S-NAP+TCNB and R-NAP+TCNB display a narrower band gap attributed to the newly formed ICT state. In contrast, the mixed rac-NAP and TCNB exhibit almost no significant change due to the strong affinity between the stereoisomers according to the Wallach's rule. Thus, S/R-NAP can be easily distinguished from rac-NAP based on significantly different optical behavior. The single crystal analysis, infrared spectroscopy, fluorescence spectroscopy, and theoretical calculation of naproxen confirm the importance of carboxyl for this differentiation in molecular packing and interaction. In addition, the esterification derivatization of naproxen achieves the manipulation of the intermolecular interaction model of racemates from the absolute Wallach's rule to a coexisting form of Wallach's rule and ICT. Further, visualized chiral purification of naproxen by the simple cocrystallization method is achieved through the collaboration of ICT and Wallach's rule.
探索手性分子（无论是单一对映体还是外消旋体）之间的分子堆积和相互作用，对于手性药物的识别和拆分至关重要。然而，目前缺乏灵敏且无损的分析方法。在此，我们报道了一种基于分子间电荷转移（ICT）的光谱技术，以揭示非手性受体1,2,4,5-四氰基苯（TCNB）与手性供体（包括S-、R-和外消旋萘普生（S/R/rac-NAP））之间相互作用的差异。在此过程中，S-NAP+TCNB和R-NAP+TCNB由于新形成的ICT态而显示出更窄的带隙。相比之下，根据瓦拉赫规则，由于立体异构体之间的强亲和力，外消旋萘普生（rac-NAP）与TCNB的混合物几乎没有显著变化。因此，基于显著不同的光学行为，可以很容易地将S/R-NAP与rac-NAP区分开来。萘普生的单晶分析、红外光谱、荧光光谱和理论计算证实了羧基在这种分子堆积和相互作用差异中的重要性。此外，萘普生的酯化衍生实现了外消旋体分子间相互作用模式从绝对瓦拉赫规则到瓦拉赫规则与ICT共存形式的调控。此外，通过ICT与瓦拉赫规则的协同作用，可以通过简单的共结晶方法实现萘普生的可视化手性纯化。
