{
  "abstract": "While salt formation is a proven strategy to overcome poor aqueous solubility and facilitate the development of active pharmaceutical ingredients, real-time monitoring of this process still lacks molecular-resolution process analytical technology (PAT). Using 8-hydroxyquinolinium salicylate as a model system, this study integrates cryogenic terahertz spectroscopy, Born–Oppenheimer molecular dynamics (BOMD), and interpretable deep learning to develop a terahertz time-domain spectroscopy (THz-TDS) workflow for stage-resolved monitoring of pharmaceutical salt formation. THz measurements (80 ∼300 K) revealed the anharmonic character of the lattice vibrations, whose dominant features were reproduced and assigned by BOMD simulations. Umbrella sampling indicated a nearly barrierless proton-transfer process (ΔG‡ = 1.7 kcal/mol) with picosecond-scale shuttling dynamics. Statistical analysis of ten kinetic models confirms first-order conversion (AIC = −151.2; n = 0.99 ± 0.02) and yielded an Arrhenius activation energy of 45.2 ± 2.3 kJ/mol for predictive process optimization. Dissolution data (n = 3; mean ± SD) showed a statistically significant 2.0–2.6-fold enhancement across pH 1.2, 6.8, and 7.4, as assessed by Welch’s t test and two-way ANOVA with Tukey’s HSD test (p < 0.001). The interpretable CNN achieved 98.2% hold-out test accuracy and used SHAP to link decisions to chemical fingerprint bands. Overfitting was evaluated through spectral dimensionality reduction, dropout, a stratified training/test split, 5-fold cross-validation, leave-one-batch-out cross-validation, and external batches under shifted thermal conditions, with accuracy retained at ≥ 92.7%. These results support a proof-of-concept, interpretable THz-TDS PAT workflow with molecular-level resolution.",
  "abstract_shown": true,
  "affiliations": [
    "Guizhou Institute of Metrology , , ,",
    "Guizhou Normal University , , ,"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Maojiang Song",
      "orcid": "0000-0002-9613-1691"
    },
    {
      "affs": [
        0
      ],
      "name": "Fei Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ying Lu"
    },
    {
      "affs": [
        0
      ],
      "name": "Shijun Min"
    },
    {
      "affs": [
        1
      ],
      "name": "Caixia Su"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e77bcfbnzzx92.bib",
  "cited_by": 0,
  "doi": "10.1021/acsomega.6c08659",
  "fulltext_url": null,
  "id": "e77bcfbnzzx92",
  "issns": [
    "2470-1343"
  ],
  "landing_url": "https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c08659/5454799/Terahertz-Spectroscopy-Enabled-Smart-Monitoring-of",
  "language": null,
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2208|Terahertz technology and applications"
    ]
  ],
  "openalex": "W7223072082",
  "pdf_url": "https://pubs.acs.org/doi/pdf/10.1021/acsomega.6c08659",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-20",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/e77bcfbnzzx92.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:39Z",
      "native_id": "10.1021/acsomega.6c08659",
      "source": "crossref",
      "url": "https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c08659/5454799/Terahertz-Spectroscopy-Enabled-Smart-Monitoring-of"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "issn:2470-1343",
      "subfield": "general"
    }
  ],
  "title": "Terahertz Spectroscopy-Enabled Smart Monitoring of Drug Salt Synthesis: A Case Study on 8-Hydroquinolinium Salicylate",
  "title_text": "Terahertz Spectroscopy-Enabled Smart Monitoring of Drug Salt Synthesis: A Case Study on 8-Hydroquinolinium Salicylate",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:39Z",
  "url": "https://research.draconitic.com/paper/e77bcfbnzzx92",
  "venue": "ACS Omega",
  "versions": []
}