Emin: A First-Principles Thermochemical Descriptor for Predicting Molecular Synthesizability

Lee, Andrew S.; Elliott, Sarah; Harb, Hassan; Ward, Logan; Foster, Ian; Curtiss, Larry; Assary, Rajeev S.

doi:10.1021/acs.jcim.3c01583

Title: E_min: A First-Principles Thermochemical Descriptor for Predicting Molecular Synthesizability

Journal Article · 14 February 2024 · Journal of Chemical Information and Modeling

DOI: https://doi.org/10.1021/acs.jcim.3c01583 · OSTI ID:2475465

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^[2]; Harb, Hassan ^[2];

^[2]; Foster, Ian ^[2];

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Northwestern Univ., Evanston, IL (United States)
Argonne National Laboratory (ANL), Argonne, IL (United States)

Predicting the synthesizability of a new molecule remains an unsolved challenge that chemists have long tackled with heuristic approaches. Here, in this study, we report a new method for predicting synthesizability using a simple yet accurate thermochemical descriptor. We introduce E_min, the energy difference between a molecule and its lowest energy constitutional isomer, as a synthesizability predictor that is accurate, physically meaningful, and first-principles based. We apply E_min to 134,000 molecules in the QM9 data set and find that E_min is accurate when used alone and reduces incorrect predictions of "synthesizable" by up to 52% when used to augment commonly used prediction methods. Our work illustrates how first-principles thermochemistry and heuristic approximations for molecular stability are complementary, opening a new direction for synthesizability prediction methods.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2475465

Journal Information:: Journal of Chemical Information and Modeling, Journal Name: Journal of Chemical Information and Modeling Journal Issue: 4 Vol. 64; ISSN 1549-9596

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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