Open-Source Chromatographic Data Analysis for Reaction Optimization and Screening

Abstract

Automation and digitalization solutions in the field of small molecule synthesis face new challenges for chemical reaction analysis, especially in the field of high-performance liquid chromatography (HPLC). Chromatographic data remains locked in vendors' hardware and software components, limiting their potential in automated workflows and data science applications. In this work, we present an open-source Python project called MOCCA for the analysis of HPLC−DAD (photodiode array detector) raw data. MOCCA provides a comprehensive set of data analysis features, including an automated peak deconvolution routine of known signals, even if overlapped with signals of unexpected impurities or side products. We highlight the broad applicability of MOCCA in four studies: (i) a simulation study to validate MOCCA's data analysis features; (ii) a reaction kinetics study on a Knoevenagel condensation reaction demonstrating MOCCA's peak deconvolution feature; (iii) a closed-loop optimization study for the alkylation of 2-pyridone without human control during data analysis; (iv) a well plate screening of categorical reaction parameters for a novel palladium-catalyzed cyanation of aryl halides employing O-protected cyanohydrins. By publishing MOCCA as a Python package with this work, we envision an opensource community project for chromatographic data analysis with the potential of further advancing its scope and capabilities.

Parallel multi-droplet platform for reaction kinetics and optimization

“…The responses of the various reaction components must be distinguishable from one another in the chosen analytical approach. The recently-reported MOCCA software (and other previous efforts) 57 is helping on this front in the U/HPLC space: MOCCA uses the full UV-Vis spectra recorded by diode array detectors at each timepoint, which enables deconvolution of overlapping peaks. Automated analysis could also be facilitated through the incorporation of automatic response factor estimation.…”

Innovations in crop protection towards sustainable agriculture

“…This was examined by Giulio Volpin (Bayer), who presented a new open-source chromatographic data analysis package that facilitates 'closed-loop' reaction optimization. 10 Lastly, Peter Maienfisch (CreInSol) outlined his vision for sustainable agriculture and what key issues are facing the industry. He advocated for a future where all available technologies will be utilized in unison to enable high crop yields to be obtained with minimal impact on the environment.…”

“…The focus then shifted to the impact that digitalization and automation can have on organic synthesis laboratories. This was examined by Giulio Volpin (Bayer), who presented a new open‐source chromatographic data analysis package that facilitates ‘closed‐loop’ reaction optimization 10 …”

A comparative study of transient flow rate steps and ramps for the efficient collection of kinetic data

“…Traditionally, kinetic studies were perceived to be laborious and require specialised knowledge and equipment. In recent years, however, the increasing variety and availability of 'plug and play' laboratory-scale analytical tools, 1 boosted by advances in laboratory automation, 2,3 kinetics analysis methods, 4 and software, 5,6 have substantially lowered the barrier for implementation. However, most kinetic experiments still require repetition to account for experimental and human error.…”