Accurate Determination of Enantiomeric Excess Using Raman Optical Activity

Abstract

The optical purity of a chiral sample is of particular importance to the analytical chemistry and pharmaceutical industries. In recent years, the vibrational optical activity (VOA) has become established as a sensitive and nondestructive technique for the analysis of chiral molecules in solution. However, the relatively limited accuracy in the range of about 1–2% reported in published papers and the relatively small spread of experimental facilities to date have meant that vibrational spectroscopy has not been considered a common method for determining enantiomeric excess. In this paper, we attempt to describe, in detail, a methodology for the determination of enantiomeric excess using Raman optical activity (ROA). This method achieved an accuracy of 0.05% for neat α-pinene and 0.22% for alanine aqueous solution, after less than 6 h of signal accumulation for each enantiomeric mixture, which we believe is the best result achieved to date using vibrational optical activity techniques. An algorithm for the elimination of systematic errors (polarization artifacts) is proposed, and the importance of normalizing ROA spectra to correct for fluctuations in excitation power is established. Results comparable to those obtained with routinely used chemometric analysis by the partial least squares (PLS) method were obtained. These findings show the great potential of ROA spectroscopy for the quantitative analysis of enantiomeric mixtures.

(Resonance) Raman optical activity among chiroptical spectroscopies: Quo vadis?

“…Methods of chiroptical spectroscopy have had a significant impact on the study and understanding of molecular chirality and stereochemical configurations. [31][32][33] Chiral compounds are optically active, which is manifested by their specific interaction with the components of circularly polarized light. Thus, molecular optical activity is a measurable quantity originating from the interaction of a chiral molecule and an electromagnetic wave.…”

“…24,25 In material science, these techniques facilitated the examination and understanding of novel materials, [26][27][28][29] while in life sciences, including pharmacology, they were used, for example, to study the chiral properties of biomolecules 30 and the enantiomeric purity of developed drugs. 7,8,31 Among the various chiroptical techniques, Raman Optical Activity (ROA) holds a special place as the youngest one, but with particular advantages revealing unique information about the structure of chiral samples in their native aqueous environment. The purpose of this paper is to provide a holistic, forward-looking analysis of ROA spectroscopy, with its historical development, current applications and to envision its future impact on chiroptical studies.…”

Vibrational and chiroptical analysis of blood plasma for hepatocellular carcinoma diagnostics

“…So far, only one ROA spectrometer with 532 nm excitation by default has been commercially available, but that may change soon. A new instrument 49,50 developed by Josef Kapitán with the ZEBR and Meopta-optica companies should be available soon, probably shortening the required analysis time. In addition, an excitation of 785 nm may be available in the near future, the use of which would lower the fluorescence background and would make the observation of overlapped bands possible.…”

Chirality induction and amplification in supramolecular systems exhibiting vibrational optical activity

“…2 These essential features of VOA spectroscopies make them excellent techniques to use for essential problems solved by chiroptical spectroscopies, i.e., the determination of the absolute configuration (AC) and enantiomeric excess (ee). [3][4][5][6][7][8] There are, however, areas where the potential of VOA is still barely explored such as enantioselective recognition, chiral sensing and biosupramolecular assembly.…”

“…, the determination of the absolute configuration (AC) and enantiomeric excess (ee). 3–8 There are, however, areas where the potential of VOA is still barely explored such as enantioselective recognition, chiral sensing and biosupramolecular assembly.…”