{
  "abstract": "The selective binding of Sr2+ over Ca2+ is very important for the development of chelating agents capable of selectively targeting radiostrontium in biological and environmental settings. Explicit-solvent molecular dynamics, Funnel-Metadynamics (Fun-MetaD), and density functional theory calculations were applied to resolve the molecular pathway of Ca2+ and Sr2+ binding by EDTA, Kryptofix 22, and Decorporol. EDTA was used as a benchmark system to validate the reparameterized force field protocol based on Minimal Basis Iterative Stockholder partial charges. The resulting relative free energy profiles reproduced the expected stronger stabilization of Ca2+ than Sr2+ by EDTA. Kryptofix 22 was included as an unfunctionalized diaza-18-crown-6 reference. Fun-MetaD profiles did not show a deeply stabilized contact-bound state. Higher concentration ITC measurements revealed weak, entropy-dominated Sr2+ association, while no reliable Ca2+ binding could be extracted under the same conditions. In contrast, simulations with Decorporol displayed a deeper contact-bound minimum for Sr2+, with minimum-to-bulk relative free energy differences of −113.2 ± 9.2 kJ/mol for Sr2+ compared with −98.2 ± 9.0 kJ/mol for Ca2+. Bound state integration and standard-state correction yielded binding free energies of −101.1 ± 2.1 kJ/mol for Sr2+ and −87.6 ± 6.4 kJ/mol for Ca2+, retaining the Sr2+-favoring trend. The simulations reveal that Decorporol binding proceeds through a two-step mechanism involving a solvent-shared ion-pair (SIP) intermediate followed by the formation of a deeply bound contact ion-pair (CIP) complex. The solvent-shared intermediate is not Sr2+-selective as both the Fun-MetaD profiles and density functional theory (DFT) calculations indicate similar Ca2+ and Sr2+ stability in this state. Selectivity emerges during the transition to the CIP complex, where the ion must undergo total dehydration to enter the Decorporol cavity. As Sr2+ has a more labile hydration shell, it can form the dehydrated contact-bound state more readily than Ca2+. Thus, Decorporol selectivity arises mainly from dehydration-gated stabilization of the CIP complex, rather than from initial ion recognition in the SIP state.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Chemistry, University of Miskolc, Egyetemváros A/2, H-3515 Miskolc, Hungary",
    "Higher Education and Industrial Cooperation Centre, University of Miskolc, H-3515 Miskolc, Hungary",
    "Department of Biochemistry, Eötvös Loránd University, Pázmány Péter stny 1/c, Budapest H-1117, Hungary"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Tamás Horváth",
      "orcid": "0009-0003-8246-1125"
    },
    {
      "affs": [
        0
      ],
      "name": "Milán Szőri",
      "orcid": "0000-0003-4895-0999"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Béla Viskolcz",
      "orcid": "0000-0002-0777-9569"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Zsófia Borbála Rózsa"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fr5pa29h0a9re.bib",
  "cited_by": 0,
  "doi": "10.1021/acs.jpcb.6c03989",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13726379/",
  "id": "fr5pa29h0a9re",
  "issns": [
    "1520-6106",
    "1520-5207"
  ],
  "landing_url": "https://doi.org/10.1021/acs.jpcb.6c03989",
  "language": "en",
  "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": [
    [
      "heading",
      "Article"
    ],
    [
      "heading",
      "B: Liquids; Chemical and Dynamical Processes in Solution"
    ],
    [
      "openalex",
      "1605|Supramolecular Chemistry and Complexes"
    ]
  ],
  "openalex": "W7221773600",
  "pdf_url": "https://pubs.acs.org/jpcbfk/article-pdf/doi/10.1021/acs.jpcb.6c03989/68853012/acs.jpcb.6c03989.pdf",
  "pmcid": "PMC13726379",
  "pmid": "42954622",
  "published": "2026-10-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fr5pa29h0a9re.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:22:45Z",
      "native_id": "PMC13726379",
      "source": "pmc",
      "url": "https://doi.org/10.1021/acs.jpcb.6c03989"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "openalex:1605|Supramolecular Chemistry and Complexes",
      "subfield": "organic"
    }
  ],
  "title": "From Hydration Shell to Chelate Cavity: Funnel-Metadynamics Reveals the Sr2+ Chelation Pathway of Decorporol",
  "title_text": "From Hydration Shell to Chelate Cavity: Funnel-Metadynamics Reveals the Sr2+ Chelation Pathway of Decorporol",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:21Z",
  "url": "https://research.draconitic.com/paper/fr5pa29h0a9re",
  "venue": "The Journal of Physical Chemistry. B",
  "versions": []
}