Raman optical activity (ROA) is a technique related to Raman spectroscopy that measures the difference in scattering intensity between left and right circularly polarized light in chiral molecules. Many organic molecules, including many drug components, have chirality and can be analyzed through ROA in pharmaceutical or forensic labs. However, researchers from Jagiellonian University and the Polish Academy of Sciences, along with other Polish and Czech collaborators, have discovered a potential error source for ROA spectroscopy and warn that results may be distorted if this source of interference is not taken into account.
The researchers discovered the phenomenon while studying derivatives of vitamin B12 as a potential medium for drug delivery. The researchers expected these similarly-structured chiral molecules to have similar spectra, but found that in some measurements, optical activity changed significantly as the concentration of the substances in their solutions changed. The team found that this unexpected concentration dependency could be attributed to interference from electronic circular dichroism (ECD). The resulting effect may lead to additional false Raman optical activity, leading to errors and misinterpretations of data.
The team noted that while they demonstrated this phenomenon in vitamin B12 analogs, it is also applicable to other light-absorbing chiral molecules. The researchers warned that this phenomenon should be factored into ROA investigations to prevent data distortions. Their findings were published in Angewandte Chemie.
“The left- and right-circularly polarized light is absorbed differently by a chiral medium, both before and on the focal range of the laser beam in the measurement cell,” said Malgorzata Baranska, a Jagiellonian University researcher and corresponding author on the paper. “This phenomenon has been either overlooked or misinterpreted in earlier studies.”
Baranska and her colleagues noted that the problem is not insurmountable. The interference can be computationally modeled and removed from the data, or the measurement itself can be adapted to account for the ECD effect.