Understanding Artifacts in Chiroptical Spectroscopy

Spectroscopic techniques can extract information about the chiral structure of molecules. However, because these methods typically rely on chiroptical effects that are very weak, even small errors in our control of optical polarization can induce experimental artifacts. Distinguishing these artifacts from true signals remains an important practical problem. Here, we present a comprehensive study of chiroptical artifacts using Raman optical activity (ROA) as a challenging example. ROA measures the difference in Raman scattering between right- and left-circularly polarized light. While ROA spectra can yield valuable information about the vibrational modes and handedness of a chiral molecule, ROA is particularly prone to artifacts as signals are 103−104 times smaller than in standard Raman spectroscopy. We develop a Mueller-matrix model to examine the origins of artifacts in ROA. We then combine our model with experimental examples from multiple ROA instruments to understand real-world artifacts. For example, we disprove a commonly held belief that ROA spectra that exhibit mirror symmetry about the intensity axis for an enantiomeric pair confirm a true signal. Based on our findings, we describe characteristics of common artifacts and propose a list of standard controls that researchers should perform to increase the likelihood that their data represent true signal. This work is intended as a resource for those working in chiroptical spectroscopy, providing methods to understand, identify, and avoid experimental artifacts.