Towards chiral monitoring - Quantum cascade lasers for rapid vibrational circular dichroism

Abstract

Introduction Chirality is an integral part of chemistry, being present in small molecules and biological macromolecules like proteins.[1] It is accessible by specialised techniques, among them nuclear magnetic resonance and X-ray crystallography. However, if a label and pre-treatment free technique is needed, only chiroptical spectroscopy techniques, like Vibrational Circular Dichroism (VCD) are worth considering. VCD operates in the infrared region and is therefore broadly applicable for structure elucidation. Unfortunately, VCD is characterised by weak signal amplitudes (10-5 – 10-6 compared to classical absorbance).[1] Consequently, typical measurements take several hours to achieve satisfactory signal to noise ratios.

Methods To overcome the limitations of VCD, a quantum cascade laser (QCL) based VCD setup was constructed. The inherent linear polarised emission of the QCL was directly used for polarisation modulation spectroscopy. To deal with the noise introduced by the QCL, a balanced detection scheme was applied. This technique compensates the laser noise and allows the leveraging of the QCL to its full potential. As a result of these modifications, it was possible to collect VCD spectra with a low noise floor and relatively high spectral resolution within measurement times below 3 minutes.

Results We report low noise VCD spectra of model molecules in solution with a time resolution significantly higher than the state of the art. We investigated mixtures of R/S-1,1′-Bi-2-naphthol in CHCl3 at concentrations between 40 and 100 mM. The used setup was designed to simulate on-line measurements of chiral reactions, as preliminary step towards chiral monitoring. The accumulated data was subsequently evaluated in terms of enantiomeric excess prediction by multivariate statistics. The results show a satisfactory performance of QCL-VCD for fast chiral monitoring and indicate possible further applications of this technique.

Innovative aspects • Establishment of non-destructive chiral analytics with a high time resolution • Use of quantum cascade lasers for high quality vibrational circular dichroism • Preliminary steps towards on-line chiral analytics