{
  "abstract": "Rational design of crystalline materials is crucial for material science and pharmaceutical development, requiring molecular modeling as a powerful complementary tool. This study employs molecular dynamics (MD) simulations to investigate the thermal stability, structural evolution, and melting mechanisms of crystalline procaine base across a temperature range of 23 to 373 K. To evaluate potential finite-size and boundary effects, two distinct computational setups were considered: a bulk crystal model under periodic boundary conditions (System I, 600 molecules) and an isolated nanocrystal in vacuum (System II, 1188 molecules). Both systems demonstrate well-preserved long-range positional ordering from 23 to 313 K, followed by the appearance of a plastic crystalline state with enhanced rotational freedom between 323 and 333 K. At 343 K, a heterogeneous, surface-initiated phase transition to an isotropic melt occurs, which closely matches the experimental melting point of procaine free-base of 334-337 K. MD analysis reveals remarkably slow melting kinetics at 333-343 K, where a crystalline core persists for over 300 ns before complete melting at 500 ns. We found that the thermal breakdown of the crystal lattice strongly correlates with a breakage of the intermolecular hydrogen-bonding 3D network between procaine molecules. Radial distribution function (RDF) analysis shows a sharp shift in the primary amino nitrogen correlations (N10···N10) towards short-distances upon melting, whereas short-range hydrogen-bond N10···O9 distances remain spatially invariant in the liquid phase. Mean square displacement (MSD) of procaine molecules demonstrates a dramatic transition from restricted lattice vibrations below 333 K to active fluid diffusion above 343 K. These findings are accompanied by rotational autocorrelation functions transition from long-time orientational persistence in the solid state (23-333 K) to rapid exponential relaxation in the melt (343-373 K). Finally, unconstrained melting of System II produces a spherical nanodroplet driven by surface tension minimization, confirming that the performance of the developed OPLS-AA FF model.",
  "abstract_shown": true,
  "affiliations": [
    "Education and Research Institute of Chemistry",
    "V.N. Karazin Kharkiv National University",
    "Institute of Functional Materials Chemistry, State Scientific Institution ''Institute for Single Crystals'', National Academy of Sciences of Ukraine, 60 Nauky Ave., Kharkiv, Ukraine, 61072"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Viktoriia O. Chukhlib"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Viktor V. Tokariev"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Alexander Kyrychenko",
      "orcid": "0000-0002-6223-0990"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6qjdn8ay6pv5s.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15008904/v1",
  "fulltext_url": null,
  "id": "6qjdn8ay6pv5s",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008904/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1902|nanoparticles nucleation surface interactions"
    ]
  ],
  "openalex": "W7213346082",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15008904/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-16",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/6qjdn8ay6pv5s.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:19Z",
      "native_id": "10.26434/chemrxiv.15008904",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008904/v1"
    }
  ],
  "subjects": [
    {
      "field": "earth",
      "origin": "openalex:1902|nanoparticles nucleation surface interactions",
      "subfield": "atmospheric"
    }
  ],
  "title": "Towards an Accurate Atomistic Description of Procaine Crystals: Force Field Development and MD Simulation of Solid-to-Liquid Phase Transitions",
  "title_text": "Towards an Accurate Atomistic Description of Procaine Crystals: Force Field Development and MD Simulation of Solid-to-Liquid Phase Transitions",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:19Z",
  "url": "https://research.draconitic.com/paper/6qjdn8ay6pv5s",
  "venue": "ChemRxiv",
  "versions": []
}