{
  "abstract": "Phototoxicity is controlled by light absorption and access to reactive excited states, but predictive models usually encode only a single ground-state structure. Here, a physically staged representation was evaluated on 450 compounds (192 positive, 258 negative) with 10 repeated five-fold scaffold-grouped cross-validations. Structure alone gave ROC-AUC 0.745 ± 0.018 and PR-AUC 0.668 ± 0.027. Adding parent-state xTB/sTDA photophysics increased these metrics to 0.792 ± 0.012 and 0.716 ± 0.020; microstate aggregation reached 0.807 ± 0.012 and 0.726 ± 0.017, while conformer expansion plateaued at 0.808 ± 0.010 and 0.729 ± 0.017. In 10,000 paired compound bootstraps, the largest robust ranking increment was the structure-to-parent-photophysics step (ΔROC-AUC +0.0457, 95% CI +0.0274 to +0.0643). Microstates produced a smaller rank-based increment but reduced Brier error by 0.0080 (95% CI 0.0024–0.0134). Higher-level Q-Chem calculations preserved S1/T1 ordering (r = 0.946/0.931). Matched-state calculations showed large photophysical changes for avobenzone and 2-ethylanthraquinone but weak changes for pradofloxacin and ketoprofen. The results identify excited-state information as the dominant reproducible addition beyond structure and show that molecular-state effects are chemically meaningful but heterogeneous rather than universally accuracy-enhancing.",
  "abstract_shown": true,
  "affiliations": [
    "Stanford University, 415 Broadway, Redwood City, California, 94063"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Aris Tsai",
      "orcid": "0009-0004-8641-7647"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/412a01erpcqz9.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15009615/v1",
  "fulltext_url": null,
  "id": "412a01erpcqz9",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009615/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",
      "1703|Computational Drug Discovery Methods"
    ]
  ],
  "openalex": "W7214706204",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15009615/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-29",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/412a01erpcqz9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:21Z",
      "native_id": "10.26434/chemrxiv.15009615",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009615/v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "source:chemrxiv",
      "subfield": "general"
    }
  ],
  "title": "Excited-State Photophysics Improves Scaffold-Robust Phototoxicity Prediction and Reveals Compound-Specific State Effects",
  "title_text": "Excited-State Photophysics Improves Scaffold-Robust Phototoxicity Prediction and Reveals Compound-Specific State Effects",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:21Z",
  "url": "https://research.draconitic.com/paper/412a01erpcqz9",
  "venue": "ChemRxiv",
  "versions": []
}