Applied Circular Dichroism: A Facile Spectroscopic Tool for Configurational Assignment and Determination of Enantiopurity

Abstract

In order to determine if electronic circular dichroism (ECD) is a good tool for the qualitative evaluation of absolute configuration and enantiopurity in the absence of chiral high performance liquid chromatography (HPLC), ECD studies were performed on several prescriptions and over-the-counter drugs. Cotton effects (CE) were observed for both S and R isomers between 200 and 300 nm. For the drugs examined in this study, the S isomers showed a negative CE, while the R isomers displayed a positive CE. The ECD spectra of both enantiomers were nearly mirror images, with the amplitude proportional to the enantiopurity. Plotting the differential extinction coefficient (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi mathvariant="normal">Δ</mml:mi><mml:mi>ε</mml:mi></mml:math>) versus enantiopurity at the wavelength of maximum amplitude yielded linear standard curves with coefficients of determination (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mrow><mml:msup><mml:mrow><mml:mi>R</mml:mi></mml:mrow><mml:mrow><mml:mn>2</mml:mn></mml:mrow></mml:msup></mml:mrow></mml:math>) greater than 97% for both isomers in all cases. As expected, Equate, Advil, and Motrin, each containing a racemic mixture of ibuprofen, yielded no chiroptical signal. ECD spectra of Suphedrine and Sudafed revealed that each of them is rich in 1S,2S-pseudoephedrine, while the analysis of Equate vapor inhaler is rich in R-methamphetamine.