Chiral Detection in High-Performance Liquid Chromatography by Vibrational Circular Dichroism

Abstract

A novel chiral detector for high-performance liquid chromatography has been developed. This detector is based on the measurement of circular dichroism of chiral effluents in the infrared region, i.e., vibrational circular dichroism (VCD). In this instrument, a solid-state spectral tunable (from 2.4 to 3.5 microns) F-center laser was used as the light source. The linearly polarized laser beam was converted into left circularly polarized light (LCPL) and right circularly polarized light (RCPL) at 42 kHz by means of a photoelastic modulator. The intensity of the LCPL and RCPL transmitted through the sample was measured by a liquid nitrogen cooled indium antimonide detector. Double modulation was employed to reduce the noise associated with the laser beam. Specifically, the linearly polarized laser beam, prior to being converted to CPL, was modulated at 85 Hz by a mechanical chopper. Demodulation and amplification were accomplished with the use of two lock-in amplifiers. In its present configuration, the instrument can be used to measure the VCD of O-H groups. Its sensitivity is so high that it was able, for the first time, to detect chirally (with limits of detection of micrograms) (R)- and (S)-2,2,2-trifluoro-1-(9- anthryl)ethanol and (R)- and (S)-benzoin when these compounds were chromatographically separated from the corresponding racemic mixtures by a Chiralcel-OD column. The main advantage of this chiral detector is, however, its universality; i.e., it can be used to virtually detect any chiral compounds which has O-H group (e.g, aliphatic alcohols such as 2-octanol).

INFRARED AND RAMAN VIBRATIONAL OPTICAL ACTIVITY: Theoretical and Experimental Aspects

“…The power of VCD and ROA to serve as sensitive in situ indicators of enantiomeric excess in samples of chiral molecules has been demonstrated for both VCD (209) and ROA (156,210). VCD has also been used as a chiral detector for the effluent from a high-performance liquid chromatograph (211). OUTLOOK VOA is coming into its own as an important experimental and theoretical tool for determining the absolute conformational stereochemistry of chiral molecules in solution and disordered phases.…”

CF3: an overlooked chromophore in VCD spectra. A review of recent applications in structural determination

“…Before moving to the last part of this mini-review, we should remind that remarkable work on CF 3 containing molecules has been carried out by Merten et al, by Monde et al and again by the Polavarapu group. [48][49][50][51][52] The last part of this work focuses on two new cases of VCD and IR spectra (compounds 8 and 10 of Scheme 1) with a special attention to C-F stretching modes:…”

Reliable assay of extreme enantiomeric purity values by a new circular dichroism based HPLC detection system

“…7,14,15 However, CD spectrometer has long been plagued with detection sensitivity problems because of the inherently small magnitude of CD signals with respect to the absorbance. 16,17 This was particularly true when it was applied to real cases of drug analysis, having anisotropy factor values of the order of 10 −3 or less. Quite high sensitivity has been reported for CD detection at a single wavelength.…”

“…[7][8][9] Some reports concern also the CD monitoring in the near-IR 21 or vibrational region. 17,22 The analytical applicability of scattered circularly polarized Raman optical activity has been also investigated. 23 The peculiar advantages in the use of CD baseddetection systems have been reviewed by several authors.…”