{
  "problem": {
    "id": "prb_hpxuugjiw8",
    "slug": "ord-grosjean-2025-bspa-fragment-array-synthesis",
    "title": "Efficient large-scale exploration of fragment hit progression by exploiting binding-site purification of actives (B-SPA) through combining multi-step array synthesis and HT crystallography.",
    "summary": "Curate this paper's reaction data into a validated Open Reaction Database dataset. ACIE 2025, DOI 10.1002/anie.202424373. About 1,876 reactions · HTE synthesis. ORD wishlist priority Medium, difficulty Normal. Source data: machine-readable files in an open repository.",
    "structure": "SOLVE"
  },
  "revision": {
    "sealing": null,
    "id": "prv_97t0r4zypo",
    "problem_id": "prb_hpxuugjiw8",
    "revision_number": 1,
    "statement_md": "# Curate this paper into an ORD dataset\n\nBuild an Open Reaction Database (ORD) dataset of the reactions reported in:\n\n- **Paper:** Efficient large-scale exploration of fragment hit progression by exploiting binding-site purification of actives (B-SPA) through combining multi-step array synthesis and HT crystallography.\n- **Authors:** Harold Grosjean, Anthony Aimon, Storm Hassell‐Hart et al.\n- **Published:** ACIE, 2025-02-11\n- **DOI:** [10.1002/anie.202424373](https://doi.org/10.1002/anie.202424373)\n- **ORD wishlist card:** [open on GitHub](https://github.com/orgs/open-reaction-database/projects/11?pane=issue&itemId=126570023)\n\nThe reference input `card` holds these facts, the source-data locations and the notes below in machine-readable form.\n\n## Scope\n\nEvery reaction the paper reports with its data (the wishlist estimates about 1,876 reactions; HTE synthesis): inputs with amounts and roles, conditions, workups, outcomes and provenance, following the `ord-curation` Skill. Submit one ORD Dataset for the paper; if its data come from several screens or methods, keep them together and say so in the dataset description.\n\n## Source data\n\nThis is the B-SPA fragment-progression study (PHIP(2)). Crude reaction mixtures were made by multi-step array synthesis (up to 5 steps) on an OpenTrons OT-1 liquid handler and soaked into crystals for HT crystallography. Source data: Zenodo record 7586212 (CC-BY-4.0). 'X-ray and reaction QC data summary.csv' has 2262 rows, and every row has product SMILES. Reactant 1/2 SMILES are present in 2258 rows and Reactant 3 SMILES in 1746. The Synthesis/LCMS outcome column is qualitative. Observed values: success ~1019, fail ~1024, plus 'trace', 'no ms', 'QC not found', 'to fill' and 'N/D'. The Yield column is mostly '0%', 'not calculated' or blank. Conditions are not in the CSV. Take them from the paper/preprint and the Opentrons protocol scripts (zip on the same record). Chemistries vary by iteration/series: urea formation from imidazolium-activated carbamoyl reagents, sulfonamide/amide couplings, Chan-Lam N-arylation and esters. Expect one reaction template per series. Crystallography, PanDDA and biophysics columns (Kd etc.) are not reaction data and should not be encoded as reaction outcomes. The paper reports >1800 enumerated compounds, while the CSV has 2262 rows. Document how rows are selected or deduplicated, and how rows with 'to fill', 'QC not found' or 'N/D' outcomes are treated.\n\nKnown locations:\n\n- [https://zenodo.org/records/7586212](https://zenodo.org/records/7586212): Zenodo record (concept DOI 10.5281/zenodo.7586211; record title uses the earlier manuscript title 'High-throughput crystallography for rapid early-stage fragment growth from crude arrays by low-cost robotics'). Files: 'X-ray and reaction QC data summary.csv' (1.0 MB, 2262 rows; columns include… (license: CC-BY-4.0)\n- [https://doi.org/10.26434/chemrxiv-2023-6m2s0-v2](https://doi.org/10.26434/chemrxiv-2023-6m2s0-v2): ChemRxiv preprint (procedures/conditions) (license: unknown (not checked))\n- [https://doi.org/10.1002/anie.202424373](https://doi.org/10.1002/anie.202424373): Angewandte Chemie article (Wiley; not fetched) (license: CC-BY (article, per OpenAlex))\n\n## Pitfalls\n\nOutcomes are qualitative (LCMS product detected yes/no/trace), with no yields for most rows. Reactions are multi-step and telescoped on crude mixtures, so each row is a sequence, not a single reaction. There are several reaction templates across iterations. Some reagents are salts (imidazolium iodides). Conditions must be joined in from the scripts and the paper, not from the CSV. Some outcome cells are placeholders ('to fill').\n\n## Deliver\n\n- `dataset`: the ORD Dataset, compressed (`.binpb.gz`, `.pb.gz`, `.txtpb.gz`, `.pbtxt.gz` or `.parquet`), citing the DOI above in every reaction's provenance, with no dataset or reaction IDs.\n- `sources`: a `.zip` with a `README.md` (which tables or files each part came from, how structures were checked), the template and spreadsheet or the script or notebook that rebuild the dataset, and `validation.txt`, the output of ORD's validator (ord-schema 0.8.3) on the `dataset` file.\n\n## Before you start\n\nOpen the wishlist card. If it is no longer Available, someone has reserved or started it: coordinate with them or choose another paper. Get the source data only through legitimate channels (the publisher's Supporting Information, the repositories above, or the authors). Submitting the finished dataset to ORD, and ORD's separate Dataset Rewards program, follow ORD's own rules.\n",
    "context_md": null,
    "benchmark": null,
    "verifier_contract_id": "vct_4t6ri8zibj",
    "verifier_input_bindings": [
      {
        "key": "card",
        "content_hash": "sha256:1a59598b8c4504e928dac9f85241a08dc204eb3c55637666ea2fc353c08e3aaf",
        "size_bytes": 4071,
        "media_type": "application/json",
        "filename": "card.json"
      }
    ],
    "skill_refs": [
      {
        "skill_version_id": "skv_k5sivlohu1",
        "requirement": "required"
      }
    ],
    "changelog_md": null,
    "created_by_user_id": "usr_llep2e937g",
    "created_at": "2026-09-25T19:27:21Z"
  }
}