{
  "abstract": "Background : Oxidative modification of low-density lipoprotein (LDL) contributes to atherogenesis, with polyunsaturated fatty acids (PUFAs) as its main chemical target. Vitamin E is an effective chainbreaking antioxidant in vitro, yet large clinical trials showed no cardiovascular benefit. We calculated bond dissociation energies (BDEs) of model compounds to quantify the underlying thermodynamics. Methods : Density functional theory calculations (PySCF; B3LYP/6-311+G(d,p)//B3LYP/6-31G*, scaled zero-point energy, 0K) were performed for butane, 1,4-pentadiene, phenol, catechol and methyl hydroperoxide. Vitamin E was not calculated at the relaxed level; published values were used. A truncated tocopherol model (5,7,8-trimethylchroman-6-ol) was run at screening level only (B3LYP/6-31+G*, unrelaxed geometries, no zero-point correction), with phenol at the same level. Results : The bis-allylic C–H bond of 1,4-pentadiene (68.2 kcal/mol) was 28.3 below that of butane (96.5). Catechol O–H (73.4) was 8.4 below phenol (81.8). The hydroperoxide model (79.6) fell 2.2 below phenol, opposite to the approximate literature order; the cause was not investigated. In screening calculations the tocopherol model was 9.0 below phenol. Published values place α-tocopherol O–H at about 77 to 78 kcal/mol, about 10 below phenol, the same direction as our screening gap. Computed values were 1.7 to 8.6 kcal/mol below approximate literature values, so gaps and ordering, not absolute values, are interpreted. Conclusions : The calculations quantify the thermodynamic basis for PUFA vulnerability and for the stronger hydrogen donation of polyphenol-type O–H bonds. They do not by themselves show donation to peroxyl radicals. Bond energies cannot explain the clinical trial results; kinetics, LDL localization and tocopherol-mediated peroxidation must be considered. No clinical outcomes or biomarkers were computed.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "name": "Yadlapalli Anirudh",
      "orcid": "0009-0000-8211-6856"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/09zn8cb51ag4a.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010283/v1",
  "fulltext_url": null,
  "id": "09zn8cb51ag4a",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010283/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",
      "1605|Free Radicals and Antioxidants"
    ]
  ],
  "openalex": "W7221526033",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010283/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/09zn8cb51ag4a.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:22Z",
      "native_id": "10.26434/chemrxiv.15010283",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010283/v1"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Free Radicals and Antioxidants",
      "subfield": "organic"
    }
  ],
  "title": "Density Functional Theory Bond Dissociation Energies of Model Compounds Relevant to LDL Oxidation: Bis-Allylic C–H, Phenolic O–H and Hydroperoxide O–H Bonds",
  "title_text": "Density Functional Theory Bond Dissociation Energies of Model Compounds Relevant to LDL Oxidation: Bis-Allylic C–H, Phenolic O–H and Hydroperoxide O–H Bonds",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:22Z",
  "url": "https://research.draconitic.com/paper/09zn8cb51ag4a",
  "venue": "ChemRxiv",
  "versions": []
}