Platinum Polyoxoniobate: Stability, Cytotoxicity, and Cellular Uptake

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Abstract

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. Quantum mechanical modeling showed 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 Escherichia 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. Atomic emission spectroscopy for Pt and Nb showed that Pt-PON1 is efficiently taken up by human cells in a stoichiometry corresponding to the original complex. Thus, platinum polyoxometalates, provided their solubility can be improved, may be considered as promising antitumor agents.

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About the authors

A. V. Yudkina

SB RAS Institute of Chemical Biology and Fundamental Medicine; Synchrotron Radiation Facility – Siberian Circular Photon Source SKIF, SB RAS Boreskov Institute of Catalysis

Author for correspondence.
Email: ayudkina@niboch.nsc.ru
Russian Federation, prosp. Lavrentieva 8, Novosibirsk 630090; Nikolskiy prosp. 1, Kol’tsovo, Novosibirsk Region 630559

I. P. Vokhtantsev

SB RAS Institute of Chemical Biology and Fundamental Medicine

Email: ayudkina@niboch.nsc.ru
Russian Federation, prosp. Lavrentieva 8, Novosibirsk 630090

D. A. Rychkov

Synchrotron Radiation Facility – Siberian Circular Photon Source SKIF, SB RAS Boreskov Institute of Catalysis; SB RAS Institute of Solid State Chemistry and Mechanochemistry

Email: ayudkina@niboch.nsc.ru
Russian Federation, Nikolskiy prosp. 1, Kol’tsovo, Novosibirsk Region 630559; ul. Kutateladze 18, Novosibirsk 630128

V. V. Volchek

SB RAS Nikolaev Institute of Inorganic Chemistry

Email: ayudkina@niboch.nsc.ru
Russian Federation, prosp. Lavrentieva 3, Novosibirsk 630090

P. A. Abramov

SB RAS Nikolaev Institute of Inorganic Chemistry

Email: ayudkina@niboch.nsc.ru
Russian Federation, prosp. Lavrentieva 3, Novosibirsk 630090

M. N. Sokolov

SB RAS Nikolaev Institute of Inorganic Chemistry

Email: ayudkina@niboch.nsc.ru
Russian Federation, prosp. Lavrentieva 3, Novosibirsk 630090

D. O. Zharkov

Novosibirsk State University

Email: ayudkina@niboch.nsc.ru
Russian Federation, ul. Pirogova 2, Novosibirsk 630090

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2. Fig. 1. Modeling of formation of platinum polyoxoniobate adduct with guanine. (a) is the structure of bicenter platinum polyoxoniobate [(Nb6O19)2{Pt(OH)2}2]12− (Pt-PON1); (b) is the structure of monocenter platinum polyoxoniobate [Pt(Nb6O19)2]12− (Pt-PON2). The structures are given according to [24]; (c) is the structure of the Gua–Pt–PON1 adduct; (d) is the N7[Gua]-Pt binding energy profile calculated at the level of B3LYP theory with a mixed base set of 6-31 and LANL2DZ.

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3. 2. Graph of the dependence of E. coli cell survival on the concentration of Pt-PON1 during short-term treatment. The average values and standard deviation (n = 3) for strains DH5a and XL1-Blue are given.

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4. 3. Graph of the dependence of human cell survival on the concentration of cisplatin (a) and Pptp ON 1 (b). The average values and standard deviation (n = 5) for lines A-549, MCF-7 and HEK293T are shown.

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5. 4. Formation of amorphous precipitate (a) and monoclinic crystals (b) during the interaction of Pt-PON1 with cellular media.

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6. 5. The content of Nb (a) and Pt (b) in HEK293T cells after incubation with 5 microns (columns 1, 2, 5, 6) and 15 microns of Pt-PON1 (columns 3, 4, 7, 8). After incubation, the cells were washed from the compound 2 times with PBS (columns 1, 3, 5, 7) or 3 times PBS (columns 2, 4, 6, 8).

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