eprintid: 10204969 rev_number: 8 eprint_status: archive userid: 699 dir: disk0/10/20/49/69 datestamp: 2025-02-19 08:19:04 lastmod: 2025-02-19 08:19:04 status_changed: 2025-02-19 08:19:04 type: article metadata_visibility: show sword_depositor: 699 creators_name: Bachtiger, Fabienne creators_name: Rahimee, Aliff creators_name: Li, Lunna creators_name: Salvalaglio, Matteo title: Solution Thermodynamics of <sc>l</sc>-Glutamic Acid Polymorphs from Finite-Sized Molecular Dynamics Simulations ispublished: pub divisions: UCL divisions: B04 divisions: F43 keywords: Science & Technology, Technology, Engineering, Chemical, Engineering, PARTICLE MESH EWALD, NUCLEATION, TRANSFORMATION, CRYSTALS, GROWTH, SINGLE note: This article is licensed under CC-BY 4.0 https://creativecommons.org/licenses/by/4.0/ abstract: Efficiently obtaining atomic-scale thermodynamic parameters characterizing crystallization from solution is key to developing the modeling strategies needed in the quest for digital design strategies for industrial crystallization processes. Based on the thermodynamics of crystal nucleation in confined solutions, we develop a simulation framework to efficiently estimate the solubility and surface tension of organic crystals in solution from a few unbiased molecular dynamics simulations at a reference temperature. We then show that such a result can be extended with minimal computational overhead to capture the solubility curve. This enables an efficient and self-consistent estimate of the solubility and limit of solution stability associated with crystal nucleation in molecular systems from equilibrium molecular dynamics without the need for sophisticated free energy calculations. We apply our analysis to investigate the relative thermodynamic stability and aqueous solubility of the α and β polymorphs of l-glutamic acid. Our analysis enables an efficient appraisal of emergent ensemble properties associated with the thermodynamics of nucleation from solutions against experimental data, demonstrating that while the absolute solubility is still far from being quantitatively captured by an off-the-shelf point charge transferable force field, the relative polymorphic stability and solubility obtained from finite temperature simulation are consistent with the experimentally available information on glutamic acid. We foresee the ability to efficiently obtain solubility information from a limited number of computational experiments as a critical component of high-throughput polymorph screenings. date: 2025-01-07 date_type: published publisher: AMER CHEMICAL SOC official_url: https://doi.org/10.1021/acs.iecr.4c02558 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2353413 doi: 10.1021/acs.iecr.4c02558 medium: Electronic-eCollection lyricists_name: Salvalaglio, Matteo lyricists_id: MSALV72 actors_name: Salvalaglio, Matteo actors_id: MSALV72 actors_role: owner funding_acknowledgements: EP/R018820/1 [Crystallization in the Real World EPSRC Programme Grant]; EP/X033139/1 [ht-MATTER UKRI Frontier Research Guarantee Grant] full_text_status: public publication: Industrial & Engineering Chemistry Research (IECRED) volume: 64 number: 2 pagerange: 1309-1318 pages: 10 event_location: United States issn: 0888-5885 citation: Bachtiger, Fabienne; Rahimee, Aliff; Li, Lunna; Salvalaglio, Matteo; (2025) Solution Thermodynamics of <sc>l</sc>-Glutamic Acid Polymorphs from Finite-Sized Molecular Dynamics Simulations. Industrial & Engineering Chemistry Research (IECRED) , 64 (2) pp. 1309-1318. 10.1021/acs.iecr.4c02558 <https://doi.org/10.1021/acs.iecr.4c02558>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10204969/1/Solution%20Thermodynamics%20of%20l-Glutamic%20Acid%20Polymorphs%20from%20Finite-Sized%20Molecular%20Dynamics%20Simulations.pdf