{
  "abstract": "Passive membrane permeation depends on both solute partitioning and coordinate-dependent mobility, but their separate and spatial-coupling contributions are rarely quantified within a common resistance framework. CNFD (6b,7-dihydro-5H-cyclopenta[b]naphtho[2,1-d]furan-5,6(9aH)-dione), a semisynthetic naphthoquinone with low-micromolar cytotoxicity and tumor-growth inhibition in preclinical models, was examined in a four-component model lipid bilayer. Established simulated tempering-enhanced umbrella sampling, WHAM, the Hummer positional-autocorrelation formalism, and the inhomogeneous solubility-diffusion model were combined. Three independent replicas yielded favorable interfacial partitioning (-4.66 kJ mol-1) and a positive membrane-center free energy (+12.36 kJ mol-1). Controlled profile substitutions showed that PMF heterogeneity and position-dependent diffusion amplified CNFD resistance by factors of 10.54 and 14.89, respectively, whereas their residual spatial-coupling factor was 1.134. The PMF maximum and diffusion minimum were separated by 2.14 nm. The primary intrinsic Peff was 9.09 × 10-2 cm s-1. Applying the same analysis to β-lapachone and plumbagin identified contrasting resistance regimes, with plumbagin combining a favorable center PMF with much lower central resistance localization. These results show how spatially separated free-energy and mobility landscapes govern intrinsic lipid-phase permeation.",
  "abstract_shown": true,
  "affiliations": [
    "Faculty of Pharmaceutical Sciences, Federal University of Amazonas, Manaus, Amazonas69080-900, Brazil.",
    "Center for Innovation in Artificial Intelligence for Health (CIIA - Saúde/UFMG), Belo Horizonte, Minas Gerais31270-901, Brazil."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Fábio J N Ferreira",
      "orcid": "0000-0001-7251-8026"
    },
    {
      "affs": [
        0
      ],
      "name": "Tallita Marques Machado"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Fernanda Guilhon-Simplicio"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cmq2jqybqyftc.bib",
  "cited_by": 0,
  "doi": "10.1021/acs.jpcb.6c02574",
  "fulltext_url": "https://europepmc.org/articles/PMC13592021",
  "id": "cmq2jqybqyftc",
  "issns": [
    "1520-6106",
    "1520-5207"
  ],
  "landing_url": "https://europepmc.org/article/MED/42915338",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Lipid Membrane Structure and Behavior"
    ]
  ],
  "openalex": "W7168168409",
  "pdf_url": "https://europepmc.org/articles/PMC13592021?pdf=render",
  "pmcid": "PMC13592021",
  "pmid": "42915338",
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cmq2jqybqyftc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:02Z",
      "native_id": "MED:42915338",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42915338"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Lipid Membrane Structure and Behavior",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Free-Energy and Position-Dependent Diffusion Profiles Shape Passive Permeation of a Semisynthetic Naphthoquinone across a Model Lipid Bilayer.",
  "title_text": "Free-Energy and Position-Dependent Diffusion Profiles Shape Passive Permeation of a Semisynthetic Naphthoquinone across a Model Lipid Bilayer.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:02Z",
  "url": "https://research.draconitic.com/paper/cmq2jqybqyftc",
  "venue": "The journal of physical chemistry. B",
  "versions": []
}