Issue 5, 2024

Establishing the main determinants of the environmental safety of catalytic fine chemical synthesis with catalytic cross-coupling reactions

Abstract

Fine chemical synthesis is the key area of industry and academic research, with a strong focus on catalytic C–C bond formation targeted at drug design, biologically active compounds and new materials. Until recently, such catalytic technologies had been employed without a rigorous analysis of a plausible ecological impact, which is now a key question that cannot be neglected. In this work, we experimentally classified the complete range of harmful compounds used in common Sonogashira and Mizoroki–Heck cross-coupling reactions by means of bio-Profiles (bio-Strips) built on the basis of 24 h CC50 values of individual reaction substances measured in three cell lines of different origins. For a comprehensive evaluation, 864 individual reactions and 2592 bio-Strips supplemented with bio-factors (BFs) and cytotoxicity potentials (CPs) were evaluated. According to the results, from the viewpoint of the contribution of the tested chemicals to the “overall cytotoxicity” of the synthetic routes analyzed, close attention should be paid to the selection of the catalysts due to their high cytotoxicity and to the solvents because they are used in significant quantities in the reaction. The choice of the base can also have a significant impact on the bio-Profile, whereas the effect of the starting materials seems lower in comparison. We also describe a new approach to unambiguous and quantitative comparisons of biological objects (in this case, cell cultures) in terms of their response to the continually varying conditions in reaction systems. In addition, we support the earlier-suggested notion that the choice of a particular cell line for CC50 measurements can be of secondary importance for the resulting bio-Strips. Nevertheless, the actual cytotoxicity of a given compound should not be ignored when selecting the participant components for a target reaction, as evidenced by the newly introduced “tumor selectivity index” (tSI) of individual chemicals. A detailed analysis of these two practically important catalytic reactions also provides a guide and a global view for assessing the bio-risks of other catalytic processes.

Graphical abstract: Establishing the main determinants of the environmental safety of catalytic fine chemical synthesis with catalytic cross-coupling reactions

Supplementary files

Article information

Article type
Paper
Submitted
23 Nov 2023
Accepted
17 Jan 2024
First published
30 Jan 2024

Green Chem., 2024,26, 2825-2841

Establishing the main determinants of the environmental safety of catalytic fine chemical synthesis with catalytic cross-coupling reactions

K. S. Egorova, A. E. Kolesnikov, A. V. Posvyatenko, A. S. Galushko, R. R. Shaydullin and V. P. Ananikov, Green Chem., 2024, 26, 2825 DOI: 10.1039/D3GC04572B

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements