Work

At-line determination of the enantiomeric excess in multi-component chiral samples using Raman optical activity (ROA)

Year: 2025

Type: article

Abstract: Addressing the need of pharmacological industry for the effective analysis of chiral drugs in situ in solution, we have designed and constructed the at-line setup based on Raman Optical Activity (ROA) and equipped with the 3D-printed flow reactor dedicated for fast in situ and in-flow analysis of chiral compounds. We have validated our approach by the determination of the enantiomeric excess (EE) of pure and multi-component chiral samples showing that the developed solution combines the excellent stereosensitivity, possibility to measure chiral samples in-flow, and a rather unique capability of direct discrimination of components of chiral mixtures. The quantitative analysis based on Partial Least Squares (PLS) regression has demonstrated that the accuracy and precision of the method is very high with the average prediction error from cross-validation (RMSECV) not exceeding 1.35% (for R2 at least 99.95) for ROA spectra recorded in 20 minutes. In the long-term, our solution paves the way toward operando (in-line) ROA, enabling real-time monitoring of chirality in reaction mixtures.

Source: Analytica Chimica Acta

DOI: 10.1016/j.aca.2025.344727

Authors: Karolina Kwiecień, Piotr Putyra, Agnieszka Kaczor

Institutions: Jagiellonian University, Łukasiewicz Research Network - Institute of Microelectronics and Photonics, Lukasiewicz Research Network - Krakow Institute of Technology

Language: English

Topic: Molecular spectroscopy and chirality

Subfield: Spectroscopy

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,270

Funders: European Commission, Ministerstwo Edukacji i Nauki