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Exploring Molecules with Low Viscosity: Using Physics-Based Simulations and De Novo Design by Applying Reinforcement Learning
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    Exploring Molecules with Low Viscosity: Using Physics-Based Simulations and De Novo Design by Applying Reinforcement Learning
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    • Nobuyuki N. Matsuzawa*
      Nobuyuki N. Matsuzawa
      Engineering Division, Panasonic Industry Co., Ltd., 1006 Kadoma, Kadoma City, Osaka 571-8506, Japan
      *Email: [email protected]
    • Hiroyuki Maeshima
      Hiroyuki Maeshima
      Engineering Division, Panasonic Industry Co., Ltd., 1006 Kadoma, Kadoma City, Osaka 571-8506, Japan
    • Keisuke Hayashi
      Keisuke Hayashi
      Engineering Division, Panasonic Industry Co., Ltd., 1006 Kadoma, Kadoma City, Osaka 571-8506, Japan
    • Tatsuhito Ando
      Tatsuhito Ando
      Engineering Division, Panasonic Industry Co., Ltd., 1006 Kadoma, Kadoma City, Osaka 571-8506, Japan
    • Mohammad Atif Faiz Afzal*
      Mohammad Atif Faiz Afzal
      Schrödinger Inc., 101 SW Main Street, Suite 1300, Portland, Oregon 97204, United States
      *Email: [email protected]
    • Kyle Marshall
      Kyle Marshall
      Schrödinger Inc., 101 SW Main Street, Suite 1300, Portland, Oregon 97204, United States
    • Benjamin J. Coscia
      Benjamin J. Coscia
      Schrödinger Inc., 101 SW Main Street, Suite 1300, Portland, Oregon 97204, United States
    • Andrea R. Browning
      Andrea R. Browning
      Schrödinger Inc., 101 SW Main Street, Suite 1300, Portland, Oregon 97204, United States
    • Alexander Goldberg
      Alexander Goldberg
      Schrödinger Inc., 9868 Scranton Road, Suite 3200, San Diego, California 92121, United States
    • Mathew D. Halls
      Mathew D. Halls
      Schrödinger Inc., 9868 Scranton Road, Suite 3200, San Diego, California 92121, United States
    • Karl Leswing
      Karl Leswing
      Schrödinger Inc., 120 West 45th Street, 17th Floor, New York, New York 10036, United States
      More by Karl Leswing
    • Mayank Misra
      Mayank Misra
      Schrödinger Inc., 120 West 45th Street, 17th Floor, New York, New York 10036, United States
      More by Mayank Misra
    • Farhad Ramezanghorbani
      Farhad Ramezanghorbani
      Schrödinger Inc., 120 West 45th Street, 17th Floor, New York, New York 10036, United States
    • Tsuguo Morisato
      Tsuguo Morisato
      Schrödinger K.K., 13F Marunouchi Trust Tower North,1-8-1 Marunouchi Chiyoda-ku, Tokyo 100-0005, Japan
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    Chemistry of Materials

    Cite this: Chem. Mater. 2024, 36, 23, 11706–11716
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    https://doi.org/10.1021/acs.chemmater.4c02929
    Published November 19, 2024
    Copyright © 2024 American Chemical Society

    Abstract

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    Molecules with viscosities lower than those of conventional organic solvents are highly sought after for applications in electrochemical devices such as batteries and capacitors. These molecules improve the electrical resistance of devices, enhancing their efficiency, especially at low temperatures. To identify new molecules with low viscosities, we conducted extensive molecular dynamics (MD) simulations on 10,000 molecules selected from the GDB-17 chemical structure database, specifically choosing molecules with fewer than 12 heavy atoms. Additionally, we performed density functional theory (DFT) calculations to determine the energies of the highest occupied molecular orbitals (HOMO) of these molecules as a surrogate for the oxidation potential. We used the data on viscosity and HOMO levels as training sets to develop machine-learning models that predict these properties. Using these models, we carried out molecular de novo design using the REINVENT method, a reinforcement-learning approach utilizing SMILES strings. This method aimed to identify molecules that minimize viscosity while maintaining sufficiently low HOMO levels for stability. The approach successfully identified new chemical structures with viscosities below 2 mPa·s and suitably low HOMO energies. We synthesized a novel compound from the top candidates and validated our predictions experimentally. The experimental results closely matched our predictions, demonstrating that combining physics-based simulations with reinforcement learning is an effective strategy for designing novel molecules with targeted properties.

    Copyright © 2024 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.chemmater.4c02929.

    • Comparison of the Green–Kubo method and the Stokes–Einstein method to calculate the viscosity of small molecules, distribution of properties of the top designed molecules from both classification and regression models, histograms comparing the training data and the generated data for HOMO energy values and viscosity values, and 1H NMR and 13C NMR spectra of 2-(1-methoxyethyl)-3-propylaziridine; chemical structures and MD- and DFT-calculated viscosities and HOMO energy levels of the REINVENT-designed molecules are also available at the section (PDF)

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    Chemistry of Materials

    Cite this: Chem. Mater. 2024, 36, 23, 11706–11716
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.chemmater.4c02929
    Published November 19, 2024
    Copyright © 2024 American Chemical Society

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