---
_id: '14603'
abstract:
- lang: eng
  text: Computing the solubility of crystals in a solvent using atomistic simulations
    is notoriously challenging due to the complexities and convergence issues associated
    with free-energy methods, as well as the slow equilibration in direct-coexistence
    simulations. This paper introduces a molecular-dynamics workflow that simplifies
    and robustly computes the solubility of molecular or ionic crystals. This method
    is considerably more straightforward than the state-of-the-art, as we have streamlined
    and optimised each step of the process. Specifically, we calculate the chemical
    potential of the crystal using the gas-phase molecule as a reference state, and
    employ the S0 method to determine the concentration dependence of the chemical
    potential of the solute. We use this workflow to predict the solubilities of sodium
    chloride in water, urea polymorphs in water, and paracetamol polymorphs in both
    water and ethanol. Our findings indicate that the predicted solubility is sensitive
    to the chosen potential energy surface. Furthermore, we note that the harmonic
    approximation often fails for both molecular crystals and gas molecules at or
    above room temperature, and that the assumption of an ideal solution becomes less
    valid for highly soluble substances.
acknowledgement: A.R. and B.C. acknowledge resources provided by the Cambridge Tier-2
  system operated by the University of Cambridge Research Computing Service funded
  by EPSRC Tier-2 capital Grant No. EP/P020259/1. P.Y.C. acknowledges support from
  the Ernest Oppenheimer Fund and the Winton Programme for the Physics of Sustainability.
article_number: '184110'
article_processing_charge: Yes (in subscription journal)
article_type: original
arxiv: 1
author:
- first_name: Aleks
  full_name: Reinhardt, Aleks
  last_name: Reinhardt
- first_name: Pin Yu
  full_name: Chew, Pin Yu
  last_name: Chew
- first_name: Bingqing
  full_name: Cheng, Bingqing
  id: cbe3cda4-d82c-11eb-8dc7-8ff94289fcc9
  last_name: Cheng
  orcid: 0000-0002-3584-9632
citation:
  ama: Reinhardt A, Chew PY, Cheng B. A streamlined molecular-dynamics workflow for
    computing solubilities of molecular and ionic crystals. <i>Journal of Chemical
    Physics</i>. 2023;159(18). doi:<a href="https://doi.org/10.1063/5.0173341">10.1063/5.0173341</a>
  apa: Reinhardt, A., Chew, P. Y., &#38; Cheng, B. (2023). A streamlined molecular-dynamics
    workflow for computing solubilities of molecular and ionic crystals. <i>Journal
    of Chemical Physics</i>. AIP Publishing. <a href="https://doi.org/10.1063/5.0173341">https://doi.org/10.1063/5.0173341</a>
  chicago: Reinhardt, Aleks, Pin Yu Chew, and Bingqing Cheng. “A Streamlined Molecular-Dynamics
    Workflow for Computing Solubilities of Molecular and Ionic Crystals.” <i>Journal
    of Chemical Physics</i>. AIP Publishing, 2023. <a href="https://doi.org/10.1063/5.0173341">https://doi.org/10.1063/5.0173341</a>.
  ieee: A. Reinhardt, P. Y. Chew, and B. Cheng, “A streamlined molecular-dynamics
    workflow for computing solubilities of molecular and ionic crystals,” <i>Journal
    of Chemical Physics</i>, vol. 159, no. 18. AIP Publishing, 2023.
  ista: Reinhardt A, Chew PY, Cheng B. 2023. A streamlined molecular-dynamics workflow
    for computing solubilities of molecular and ionic crystals. Journal of Chemical
    Physics. 159(18), 184110.
  mla: Reinhardt, Aleks, et al. “A Streamlined Molecular-Dynamics Workflow for Computing
    Solubilities of Molecular and Ionic Crystals.” <i>Journal of Chemical Physics</i>,
    vol. 159, no. 18, 184110, AIP Publishing, 2023, doi:<a href="https://doi.org/10.1063/5.0173341">10.1063/5.0173341</a>.
  short: A. Reinhardt, P.Y. Chew, B. Cheng, Journal of Chemical Physics 159 (2023).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: Simulation input files necessary to reproduce the study
  and Python data analysis scripts are available in the SI repository at https://github.com/BingqingCheng/solubility,
  and on Zenodo at http://doi.org/10.5281/zenodo.8398093.
date_created: 2023-11-26T23:00:54Z
date_published: 2023-11-14T00:00:00Z
date_updated: 2026-08-07T11:07:46Z
day: '14'
ddc:
- '530'
- '540'
department:
- _id: BiCh
doi: 10.1063/5.0173341
external_id:
  arxiv:
  - '2308.10886'
  isi:
  - '001137066700001'
  pmid:
  - '37962445'
file:
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  checksum: f668ee0d07096eef81159d05bc27aabc
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  creator: dernst
  date_created: 2023-11-28T08:39:06Z
  date_updated: 2023-11-28T08:39:06Z
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fulldoi: https://doi.org/10.1063/5.0173341
has_accepted_license: '1'
intvolume: '       159'
isi: 1
issue: '18'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
publication: Journal of Chemical Physics
publication_identifier:
  eissn:
  - 1089-7690
  issn:
  - 0021-9606
publication_status: published
publisher: AIP Publishing
quality_controlled: '1'
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researchdata_availability: yes
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supplementarymaterial: no
title: A streamlined molecular-dynamics workflow for computing solubilities of molecular
  and ionic crystals
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 159
year: '2023'
...