Abstract: The transition to eco-friendly chemical processes is a pressing concern for modern chemistry; still, current methodologies for evaluating the environmental safety of chemical reactions often fall short in terms of speed and clarity. This study presents tox-Scapes, a novel approach for rapid assessment of toxicity profiles of chemical reactions, exemplified by the widely used Buchwald–Hartwig amination. By integrating the half-maximal cytotoxic concentrations (CC50) measured in human cell lines, tox-Scapes provide a visually intuitive and quantitative tool for identifying the reaction pathways with the lowest toxicological impact. Upon screening 864 reaction routes, issued practical recommendations concerning the choice of catalyst, solvent, and other reagents were issued. In particular, the catalysts that contributed significantly to the “overall toxicity” of the reaction were identified, whereas using tetrahydrofuran as a solvent minimized the “overall toxicity”. Although the roles of the starting materials and bases were less crucial, their careful selection could further refine the environmental impact. Usage of tumor selectivity indices (tSIs) enhanced the selection of less harmful chemicals among the substances tested. The novelty of tox-Scapes lies in their ability to swiftly analyze large numbers of reaction pathways. This methodology connects fundamental chemistry and its practical implementation by enabling the rapid identification of the toxicity drivers in catalytic reactions.

Cite: Kolesnikov A.E. , Grebennikov N.O. , Romanenko K.A. , Egorova K.S. , Ananikov V.P.
Tox-Scapes: A visual and quantitative tool for selecting safer chemical reactions by means of cytotoxicity assessment
Journal of Cleaner Production. 2025. V.519. 145970 . DOI: 10.1016/j.jclepro.2025.145970 WOS Scopus OpenAlex

Identifiers:

Web of science:	WOS:001513383000006
Scopus:	2-s2.0-105007731041
OpenAlex:	W4411272537

Citing:

DB	Citing
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OpenAlex	Нет цитирований

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