Controlling the enantiomeric purity of chiral drugs is of paramount importance in pharmaceutical chemistry. Isotropic ¹H NMR spectroscopy involving chiral agents is a widely used method for discriminating enantiomers and quantifying their relative proportions. However, the relatively weak spectral separation of enantiomers (¹H Δδ_iso(R, S)) in frequency units at low and moderate magnetic fields, as well as the lack of versatility of a majority of those agents with respect to different chemical functions, may limit the general use of this approach. In this article, we investigate the analytical potential of ¹⁹F NMR in anisotropic chiral media for the enantiomeric analysis of fluorinated active pharmaceutical ingredients (API) via two residual anisotropic NMR interactions: the chemical shift anisotropy (¹⁹F-RCSA) and dipolar coupling ((¹⁹F–¹⁹F)-RDC). Lyotropic chiral liquid crystals (CLC) based on poly-γ-benzyl-L-glutamate (PBLG) show an interesting versatility and adaptability to enantiodiscrimination as illustrated for two chiral drugs, Flurbiprofen® (FLU) and Efavirenz® (EFA), which have very different chemical functions. The approach has been tested on a routine 300 MHz NMR spectrometer equipped with a standard probe (5 mm BBFO probe) in a high-throughput context (i.e., ≈10 s of NMR experiments) while the performance for enantiomeric excess (ee) measurement is evaluated in terms of trueness and precision. The limits of detection (LOD) determined were 0.17 and 0.16 μmol ml⁻¹ for FLU and EFA, respectively, allow working in dilute conditions even with such a short experimental duration. The enantiodiscrimination capabilities are also discussed with respect to experimental features such as CLC composition and temperature.

中文翻译：

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各向异性 19F NMR 用于氟化手性活性药物成分对映体分析的潜力和性能

控制手性药物的对映体纯度在药物化学中至关重要。涉及手性试剂的各向同性¹ H NMR 光谱是一种广泛使用的区分对映体和量化其相对比例的方法。然而，在低磁场和中磁场下，对映异构体 ( ¹ H Δ δ _iso ( R , S ) ) 在频率单位中的光谱分离相对较弱，并且大多数这些试剂在不同的化学功能方面缺乏通用性，可能会限制这种方法的一般使用。在本文中，我们研究了¹⁹ F NMR 在各向异性手性介质中通过两种残余各向异性 NMR 相互作用对氟化活性药物成分 (API) 进行对映体分析的分析潜力：化学位移各向异性 ( ¹⁹ F-RCSA) 和偶极耦合 ( ( ¹⁹ F – ¹⁹ F)-RDC)。基于聚-γ-苄基-L-谷氨酸 (PBLG) 的溶致手性液晶 (CLC)显示出有趣的多功能性和对映体歧视的适应性，如两种手性药物 Flurbiprofen® (FLU) 和 Efavirenz® (EFA) 所示，它们具有非常不同的化学功能。该方法已在配备标准探针（5 mm BBFO 探针）的常规 300 MHz NMR 波谱仪上进行了高通量环境（即约 10 秒 NMR 实验）的测试，而对映体过量 ( ee ) 测量的性能为从真实性和精确性方面进行评估。 FLU和EFA的检测限(LOD)分别确定为0.17和0.16 μmol ml ^-1，即使实验持续时间如此短，也允许在稀释条件下工作。还讨论了 CLC 组成和温度等实验特征的对映体辨别能力。