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Abstract：
Circular dichroism (CD) based enantiomeric excess (ee) determination assays are optical alternatives to chromatographic ee determination in high-throughput screening (HTS) applications. However, the implementation of these assays requires calibration experiments using enantioenriched materials. We present a data-driven approach that circumvents the need for chiral resolution and calibration experiments for an octahedral Fe(II) complex (1) used for the ee determination of α-chiral primary amines. By computationally parameterizing the imine ligands formed in the assay conditions, a model of the circular dichroism (CD) response of the Fe(II) assembly was developed. Using this model, calibration curves were generated for four analytes and compared to experimentally generated curves. In a single-blind ee determination study, the ee values of unknown samples were determined within 9% mean absolute error, which rivals the error using experimentally generated calibration curves.
摘要：
基于圆二色性（CD）的对映体过量（ee）测定测定法是高通量筛选（HTS）应用中色谱ee测定的光学替代方法。然而,这些测定的实施需要使用对映富集材料的校准实验。我们提出了一种数据驱动的方法，该方法避免了用于α-手性伯胺的ee测定的八面体Fe（II）络合物（1）的手性拆分和校准实验的需要。通过计算参数化分析条件中形成的亚胺配体，建立了Fe（II）组装的圆二色性（CD）响应模型。使用这个模型，生成四种分析物的校准曲线并与实验生成的曲线进行比较。在一项单盲ee测定研究中，未知样品的ee值在9%的平均绝对误差内确定，这与使用实验生成的校准曲线的误差相媲美。
