{
  "abstract": "This study reports the synthesis of neurotransmitter-inspired, biolabile mononuclear Mg(ii)/(NY1) and Ca(ii)/(NY2) metallocarboxylates of N-phthaloyl-γ-aminobutyric acid ligand (NPGABA), motivated by the growing relevance of metallocarboxylates in addressing essential metal-ion deficiencies. Extensive spectral (i.e. IR, UV-vis, ¹H-NMR, ¹³C-NMR, AAS, and ICP-AES) and analytical (SEM, micro-analysis and thermal gravimetric analysis) techniques were used to characterize and confirm the formation of the ligand and its metal carboxylate complexes. The complexes were confirmed to have the formulas [Mg(NPGABA)₂(H₂O)₂]₄ (NY1) and [Mg(NPGABA)₂(H₂O)₄] (NY2), where NPGABA is the abbreviation of the ligand in its deprotonated form. The DNA-binding interactions of the NPGABA ligand (NY0) and its alkaline earth metal carboxylate complexes with magnesium (Mg/NY1) and calcium (Ca/NY2) were investigated through a combination of biophysical, computational, and biological assays. UV-visible absorption studies revealed a significant hyperchromic effect without a bathochromic/hypsochromic shift, indicative of a non-intercalative external binding mode (i.e., minor groove binding or electrostatic interaction with the anionic sugar phosphate backbone of DNA). Binding constants (K b) were calculated by UV-vis spectroscopy at a temperature of 310.15 K and pH of 7.4 as 2.18 × 10⁵ M⁻¹ (NY0), 4.05 × 10⁵ M⁻¹ (NY1), and 4.21 × 10⁵ M⁻¹ (NY2), with Gibbs free energies (ΔG°) of -31.68, -33.28, and -33.38 kJ mol⁻¹, respectively, confirming spontaneous interactions. Similarly, fluorescence emission spectroscopic studies demonstrated eminent quenching without any shift, providing complementary evidence for the presence of external non-intercalative interactions. Accordingly, the binding constants (K b) calculated by this technique under the same physiological conditions were 1.2 × 10⁴ M⁻¹ (NY0), 4.41 × 10⁴ M⁻¹ (NY1), and 8.61 × 10⁴ M⁻¹ (NY2), with binding site numbers of 0.86 (NY0), 0.95 (NY1), and 1.01 (NY2) and Gibbs free energies (ΔG°) of -24.23, -27.56, and -29.27 kJ mol⁻¹, respectively, confirming the spontaneity of the interaction process. Molecular docking simulations against the canonical B-DNA (PDB: 1BNA) and the aromatase cytochrome P450 enzyme (PDB: 3EQM) also supported the occurrence of non-intercalative external binding interactions, with NY2 demonstrating the most favorable binding pose and energy. This non-intercalative external binding interaction was further endorsed by minute perturbation in the DNA solution viscosity and analogical consistency with classical groove binders like netropsin and distamycin A (K b ≈ 10⁵-10⁷ M⁻¹). The observed DNA binding affinity trend (NY2 > NY1 > NY0) has a direct correlation with the cytotoxic potency of the investigated compounds against triple negative breast cancer cells (MDA-MB-231). This consolidated investigation proved NY2 as a non-intercalative DNA-binding small molecule with preliminary anticancer activity, offering a strategic route for developing sustainable metallocarboxylate-based therapeutics.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, School of Natural Sciences (SNS), National University of Sciences and Technology (NUST) Islamabad 44000 Pakistan marfan@sns.nust.edu.pk nabbas.phdchem21sns@student.nust.edu.pk.",
    "Pakistan Science Foundation 1-Constitution Avenue G-5/2 Islamabad 44000 Pakistan.",
    "Department of Physics & Astronomy, School of Natural Sciences (SNS), National University of Sciences and Technology (NUST) Islamabad 44000 Pakistan.",
    "Department of Biochemistry, College of Science, King Saud University P.O. Box 2455 Riyadh 11451 Saudi Arabia."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Naeem Abbas",
      "orcid": "0000-0002-0695-840X"
    },
    {
      "affs": [
        0
      ],
      "name": "Muhammad Arfan",
      "orcid": "0000-0002-3143-6152"
    },
    {
      "affs": [
        2
      ],
      "name": "Yasir Iqbal"
    },
    {
      "affs": [
        0
      ],
      "name": "Mudassir Iqbal",
      "orcid": "0000-0002-9830-8235"
    },
    {
      "affs": [
        0
      ],
      "name": "Naeem Ahmed"
    },
    {
      "affs": [
        3
      ],
      "name": "Mona G Alharbi"
    },
    {
      "affs": [
        3
      ],
      "name": "Mansour K Gatasheh"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/90f11b3d5yd4f.bib",
  "cited_by": 0,
  "doi": "10.1039/d6ra07684j",
  "fulltext_url": "https://europepmc.org/articles/PMC13679565",
  "id": "90f11b3d5yd4f",
  "issns": [
    "2046-2069"
  ],
  "landing_url": "https://europepmc.org/article/MED/42899204",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Metal complexes synthesis and properties"
    ]
  ],
  "openalex": "W7222917943",
  "pdf_url": "https://europepmc.org/articles/PMC13679565?pdf=render",
  "pmcid": "PMC13679565",
  "pmid": "42899204",
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/90f11b3d5yd4f.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:32Z",
      "native_id": "MED:42899204",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42899204"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Metal complexes synthesis and properties",
      "subfield": "oncology"
    }
  ],
  "title": "Mononuclear Mg(ii) and Ca(ii) metallocarboxylates of N-phthaloyl-γ-aminobutyric acid: synthesis, characterization, ds-DNA binding, preliminary anticancer evaluation against MDA-MB-231 cells, and computational studies.",
  "title_text": "Mononuclear Mg(ii) and Ca(ii) metallocarboxylates of N-phthaloyl-γ-aminobutyric acid: synthesis, characterization, ds-DNA binding, preliminary anticancer evaluation against MDA-MB-231 cells, and computational studies.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:32Z",
  "url": "https://research.draconitic.com/paper/90f11b3d5yd4f",
  "venue": "RSC advances",
  "versions": []
}