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Abstract <p><b>Objective: </b>Platinum polyoxometalates are Pt (IV) complexes containing bulky cluster ligands. We have shown previously that platinum polyoxoniobate [(Nb<sub>6</sub>O<sub>19</sub>)<sub>2</sub>{Pt(OH)<sub>2</sub>}<sub>2</sub>]<sup>12−</sup> (Pt-PON1) containing two Pt centers can covalently bind DNA. Here we have addressed the structural stability of Pt-PON1 and its conjugate with guanine at the N7 position, cytotoxicity of this compound, and its accumulation in living cells. <b>Methods:</b> Quantum mechanical modeling was used to estimate the stability of Pt–guanine bond. Cytotoxicity of Pt-PON1 was evaluated by incubating various concentrations of the compound with cultured human and Escherichia coli cells, and the levels of intracellular Pt-PON1, by atomic emission spectroscopy. <b>Results and Discussion:</b> Calculations show that the Pt-PON1 complex is unstable outside the crystal lattice, while its conjugate with guanine likely undergoes structural rearrangement quite easily. A decrease in the survival of <i>E. coli</i> XL1-Blue and DH5α strains and human HEK293T and MCF-7 cell lines was observed already at 20 μM Pt-PON1 but at higher concentrations the compound was poorly soluble in biologically compatible media. The measured levels of intracellular Pt and Nb suggest that Pt-PON1 is efficiently taken up by human cells in a stoichiometry corresponding to the original complex. <b>Conclusions:</b> Platinum polyoxometalates, provided their solubility can be improved, may be considered as promising antitumor agents.</p>

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Platinum Polyoxoniobate: Stability, Cytotoxicity, and Cellular Uptake

  • 期刊论文

  • 发表日期：

    2025年4月6日

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  • A. V. Yudkina,
  • I. P. Vokhtantsev,
  • D. A. Rychkov,
  • V. V. Volchek,
  • P. A. Abramov,
  • M. N. Sokolov,
  • D. O. Zharkov

摘要

Abstract

Objective: Platinum polyoxometalates are Pt (IV) complexes containing bulky cluster ligands. We have shown previously that platinum polyoxoniobate [(Nb6O19)2{Pt(OH)2}2]12− (Pt-PON1) containing two Pt centers can covalently bind DNA. Here we have addressed the structural stability of Pt-PON1 and its conjugate with guanine at the N7 position, cytotoxicity of this compound, and its accumulation in living cells. Methods: Quantum mechanical modeling was used to estimate the stability of Pt–guanine bond. Cytotoxicity of Pt-PON1 was evaluated by incubating various concentrations of the compound with cultured human and Escherichia coli cells, and the levels of intracellular Pt-PON1, by atomic emission spectroscopy. Results and Discussion: Calculations show that the Pt-PON1 complex is unstable outside the crystal lattice, while its conjugate with guanine likely undergoes structural rearrangement quite easily. A decrease in the survival of E. coli XL1-Blue and DH5α strains and human HEK293T and MCF-7 cell lines was observed already at 20 μM Pt-PON1 but at higher concentrations the compound was poorly soluble in biologically compatible media. The measured levels of intracellular Pt and Nb suggest that Pt-PON1 is efficiently taken up by human cells in a stoichiometry corresponding to the original complex. Conclusions: Platinum polyoxometalates, provided their solubility can be improved, may be considered as promising antitumor agents.