Synthesis, crystal structure, computational and solution studies of a new phosphotetradecavanadate salt. Assessment of its effect on U87 glioblastoma cells

J Inorg Biochem. 2025 Aug:269:112882. doi: 10.1016/j.jinorgbio.2025.112882. Epub 2025 Mar 9.

Abstract

The new benzylammonium (C7H10N) salt of the phosphotetradecavanadate (PV14) anion PV14O429-, (C7H10N)6[H3PV14O42]∙7H2O (1), is synthesized under mild conditions and characterized by a combination of physicochemical techniques such as Fourier transform infrared spectroscopy, powder X-ray diffraction, elemental analyses and cyclic voltammetry. As evaluated by 51V NMR spectroscopy, at milimolar concentrations and pH ∼2.5 the PV14 anions decompose slowly, thus demonstrating kinetic stability, but at pH ∼7 this process takes place much faster. However, in the presence of human serum albumin, the 51V NMR peaks of PV14 anions broaden significantly and their decomposition becomes much slower, this being due to a direct interaction between both components. The structure of 1 is elucidated by single-crystal X-ray diffraction and reveals the presence of three-fold protonated, bicapped Keggin type [H3PV14O42]6- anions. The supramolecular interactions governing the crystal packing are further studied using the Hirshfeld surface analysis. Computational studies using density functional theory were effective in determining the electronic and protonation states of PV14 clusters, as well as the multi-electron redox behavior of compound 1 in acidic aqueous solutions. Molecular dynamics calculations confirm the high hydrophilicity and absence of aggregation between protonated PV14 anions in aqueous medium. Notably, this compound shows high inhibitory effect on the viability of the U87 glioblastoma cell line with IC50 values of 3.2 ± 0.6 μM and 1.10 ± 0.04 μM after 24 h and 72 h treatments. The mode of action of compound 1 is mediated by the pro-apoptotic process. These data provide evidence on the potential therapeutic use of PV14 compounds against glioblastoma.

Keywords: Anti-cancer activity; Density functional theory; Glioblastoma; Molecular dynamics calculations; Polyoxidometalates; X-ray diffraction.

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Density Functional Theory
  • Glioblastoma* / drug therapy
  • Glioblastoma* / metabolism
  • Glioblastoma* / pathology
  • Humans
  • Vanadates* / chemical synthesis
  • Vanadates* / chemistry
  • Vanadates* / pharmacology

Substances

  • Vanadates
  • Antineoplastic Agents