Estimation of Multicomponent Reactions' Yields from Networks of Mechanistic Steps

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Nov 28

PMID 39604372

Authors

Sara Szymkuc

Agnieszka Wolos

Rafal Roszak

Bartosz A Grzybowski

Affiliations

Soon will be listed here.

Abstract

This work describes estimation of yields of complex, multicomponent reactions (MCRs) based on the modeled networks of mechanistic steps spanning both the main reaction pathway as well as immediate and downstream side reactions. Because experimental values of the kinetic rate constants for individual mechanistic transforms are extremely sparse, these constants are approximated here using Mayr's nucleophilicity and electrophilicity parameters fine-tuned by correction terms grounded in linear free-energy relationships. With this formalism, the model trained on the mechanistic networks of only 20 - but mechanistically- and yield-diverse MCRs - transfers well to newly discovered MCRs that are based on markedly different mechanisms and types of individual mechanistic transforms. These results suggest that mechanistic-level approach to yield estimation may be a useful alternative to models that are derived from full-reaction data and lack information about yield-lowering side reactions.

Citing Articles

Systematic, computational discovery of multicomponent and one-pot reactions.

Roszak R, Gadina L, Wolos A, Makkawi A, Mikulak-Klucznik B, Bilgi Y Nat Commun. 2024; 15(1):10285.

PMID: 39604395 PMC: 11603032. DOI: 10.1038/s41467-024-54611-5.

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