Rapid Quantitative Determination of Enantiomeric Excess by Vibrational Circular Dichroism Using Noise Based Spectral Selection

ABSTRACT

Vibrational circular dichroism (VCD) spectroscopy enables direct determination of enantiomeric excess (ee), but its application as a quantitative analytical tool is limited by low signal‐to‐noise ratios (SNR), which typically require long measurement times. Using limonene as a model system, predictive models were developed by combining targeted, SNR‐based region selection with simple multivariate regression applied to both 30‐ and 5‐min acquisition data. The 30‐min data yielded excellent model performance with cross‐validated R ² of 0.997 and RMSE of ~2% ee. Notably, the 5‐min acquisition retained ~97% of predictive performance enabling a sixfold increase in throughput, albeit with increased prediction error. This work therefore demonstrates that data‐driven optimisation of spectral selection can enable reliable ee prediction with short acquisition VCD spectra, outperforming equivalent univariate models and providing a practical route toward high‐throughput chiral analysis.