Tandem Use of Optical Sensing and Machine Learning for the Determination of Absolute Configuration, Enantiomeric and Diastereomeric Ratios, and Concentration of Chiral Samples

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Authors: Zeus De los Santos, Sean MacAvaney, Katina Russell, Christian Wolf

Appeared in: Angewandte Chemie International Edition

Abstract:

Quantitative optical sensing of samples containing both enantiomeric and diastereomeric species of a chiral compound remains a major challenge. We have now developed an optical method for accurate concentration, er and dr analysis of amino alcohols based on a simple mix‐and‐measure workflow that is fully adaptable to multiwell plate technology and microscale analysis. We found that conversion of the four aminoindanol stereoisomers with salicylaldehyde to the corresponding Schiff base allows analysis of the dr based on a change in the UV maximum at approximately 420 nm that is very different for the homo‐ and heterochiral diastereomers and of the total amount (concentration) of the sample using a hypsochromic shift of another absorption band around 340 nm that is independent of the analyte stereochemistry. Subsequent in situ formation of Cu(II) assemblies in the absence and presence of base enables quantification of the er values for each diastereomeric pair by CD analysis at 340‐350 nm and 410‐420 nm, respectively. Applying linear programming (LP) methodology to optimize the weighting of UV and CD spectra and a parameter sweep (PS) algorithm for unbiased identification of optimal wavelength ranges for the most accurate and robust analysis, we were able to determine the concentration and relative amounts of each of the four stereoisomers in 20 samples of vastly different stereoisomeric compositions with an averaged absolute %error of 1.7%. The machine learning based deconvolution of the chiroptical sensing data is very practical and combined with a straightforward mix‐and‐measure workflow that exclusively uses inexpensive chemicals, eliminates protection chemistry and avoids any type of sample work‐up. Inert atmosphere and anhydrous conditions are not required, and all steps occur in the same solvent at room temperature which greatly facilitates parallel handling of hundreds of samples, automation and streamlined operation at reduced labor, waste and cost.

BibTeX @article{delossantos:angewandte2019-antimers, author = {De los Santos, Zeus and MacAvaney, Sean and Russell, Katina and Wolf, Christian}, title = {Tandem Use of Optical Sensing and Machine Learning for the Determination of Absolute Configuration, Enantiomeric and Diastereomeric Ratios, and Concentration of Chiral Samples}, year = {2019}, url = {https://onlinelibrary.wiley.com/doi/10.1002/anie.201912904}, doi = {10.1002/anie.201912904}, issue = {6}, journal = {Angewandte Chemie International Edition}, pages = {2440--2448}, volume = {59} }