{
  "abstract": "Distinguishing between salt and cocrystal forms of a drug remains challenging in multicomponent systems with ambiguous proton transfer, particularly during bulk production in the pharmaceutical industry. Here, we address this challenge by combining fluorescence lifetime imaging microscopy (FLIM) for rapid bulk-phase discrimination with Hirshfeld atom refinement (HAR) for single-crystal-level validation. This integrated FLIM–HAR approach was applied to 11 multicomponent solids derived from the pharmaceutical drugs niflumic acid, mefenamic acid, and sulfamethazine. Owing to its sensitivity to the local electronic environment and crystal-field effects, FLIM provided spatially resolved lifetime signatures that clearly distinguished salts from cocrystals, with salts consistently exhibiting longer fluorescence lifetimes. HAR unambiguously located the transferred protons, as evidenced by difference Fourier maps, thereby validating the salt–cocrystal assignments. Analysis of intermolecular interactions using the HAR models further revealed stronger interactions and tighter crystal packing in the salts, primarily arising from charge-assisted hydrogen bonding, consistent with the observed lifetime differences. The correlation between fluorescence lifetime and HAR-determined protonation state demonstrates that lifetime provides a sensitive probe of proton transfer in pharmaceutical solids. The integrated FLIM–HAR methodology therefore provides a rapid and reliable strategy for distinguishing pharmaceutical salts and cocrystals, with particular potential for bulk-phase characterization.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry",
    "Indian Institute of Technology Delhi",
    "The University of Queensland – IIT Delhi Research Academy (UQIDRA)",
    "IIT Delhi"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Amit Kumar"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Aditya Kumar Prajapati"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Sofia Arefeen Khan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Monika Gupta"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Sajesh P. Thomas",
      "orcid": "0000-0003-3552-8625"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6gpkaeg8s3f6z.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15009733/v1",
  "fulltext_url": null,
  "id": "6gpkaeg8s3f6z",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009733/v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1606|Crystallography and molecular interactions"
    ]
  ],
  "openalex": "W7215038732",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15009733/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/6gpkaeg8s3f6z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:21Z",
      "native_id": "10.26434/chemrxiv.15009733",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009733/v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1606|Crystallography and molecular interactions",
      "subfield": "physical"
    }
  ],
  "title": "Distinguishing Pharmaceutical Salts and Cocrystals by Fluorescence Lifetime Mapping and Quantum Crystallography",
  "title_text": "Distinguishing Pharmaceutical Salts and Cocrystals by Fluorescence Lifetime Mapping and Quantum Crystallography",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:21Z",
  "url": "https://research.draconitic.com/paper/6gpkaeg8s3f6z",
  "venue": "ChemRxiv",
  "versions": []
}