Heteroleptic Pd(II) and Pt(II) Complexes with Redox-Active Ligands: Synthesis, Structure, and Multimodal Anticancer Mechanism

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Heteroleptic Pd(II) and Pt(II) Complexes with Redox-Active Ligands: Synthesis, Structure, and Multimodal Anticancer Mechanism. / Romashev, Nikolai F.; Abramov, Pavel A.; Bakaev, Ivan V. et al.

In: Inorganic Chemistry, Vol. 61, No. 4, 31.01.2022, p. 2105-2118.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{26e54604ee374681a59310befd0c9401,

title = "Heteroleptic Pd(II) and Pt(II) Complexes with Redox-Active Ligands: Synthesis, Structure, and Multimodal Anticancer Mechanism",

abstract = "A series of heteroleptic square-planar Pt and Pd complexes with bis(diisopropylphenyl) iminoacenaphtene (dpp-Bian) and Cl, 1,3-dithia-2-thione-4,5-dithiolate (dmit), or 1,3-dithia-2-thione-4,5-diselenolate (dsit) ligands have been prepared and characterized by spectroscopic techniques, elemental analysis, X-ray diffraction analysis, and cyclic voltammetry (CV). The intermolecular noncovalent interactions in the crystal structures were assessed by density functional theory (DFT) calculations. The anticancer activity of Pd complexes in breast cancer cell lines was limited by their solubility. Pd(dpp-Bian) complexes with dmit and dsit ligands as well as an uncoordinated dpp-Bian ligand were devoid of cytotoxicity, while the [Pd(dpp-Bian)Cl2] complex was cytotoxic. On the contrary, all Pt(dpp-Bian) complexes demonstrated anticancer activity in a low micromolar concentration range, which was 8-20 times higher than the activity of cisplatin, and up to 2.5-fold selectivity toward cancer cells over healthy fibroblasts. The presence of a redox-active dpp-Bian ligand in Pt and Pd complexes resulted in the induction of reactive oxygen species (ROS) in cancer cells. In addition, these complexes were able to intercalate into DNA, indicating the dual mechanism of action.",

keywords = "Cisplatin",

author = "Romashev, {Nikolai F.} and Abramov, {Pavel A.} and Bakaev, {Ivan V.} and Fomenko, {Iakov S.} and Samsonenko, {Denis G.} and Novikov, {Alexander S.} and Tong, {Kelvin K.H.} and Dohyun Ahn and Dorovatovskii, {Pavel V.} and Zubavichus, {Yan V.} and Ryadun, {Aleksey A.} and Patutina, {Olga A.} and Sokolov, {Maxim N.} and Babak, {Maria V.} and Gushchin, {Artem L.}",

note = "Publisher Copyright: {\textcopyright} 2022 American Chemical Society",

year = "2022",

month = jan,

day = "31",

doi = "10.1021/acs.inorgchem.1c03314",

language = "English",

volume = "61",

pages = "2105--2118",

journal = "Inorganic Chemistry",

issn = "0020-1669",

publisher = "American Chemical Society",

number = "4",

}

RIS

TY - JOUR

T1 - Heteroleptic Pd(II) and Pt(II) Complexes with Redox-Active Ligands: Synthesis, Structure, and Multimodal Anticancer Mechanism

AU - Romashev, Nikolai F.

AU - Abramov, Pavel A.

AU - Bakaev, Ivan V.

AU - Fomenko, Iakov S.

AU - Samsonenko, Denis G.

AU - Novikov, Alexander S.

AU - Tong, Kelvin K.H.

AU - Ahn, Dohyun

AU - Dorovatovskii, Pavel V.

AU - Zubavichus, Yan V.

AU - Ryadun, Aleksey A.

AU - Patutina, Olga A.

AU - Sokolov, Maxim N.

AU - Babak, Maria V.

AU - Gushchin, Artem L.

PY - 2022/1/31

Y1 - 2022/1/31

N2 - A series of heteroleptic square-planar Pt and Pd complexes with bis(diisopropylphenyl) iminoacenaphtene (dpp-Bian) and Cl, 1,3-dithia-2-thione-4,5-dithiolate (dmit), or 1,3-dithia-2-thione-4,5-diselenolate (dsit) ligands have been prepared and characterized by spectroscopic techniques, elemental analysis, X-ray diffraction analysis, and cyclic voltammetry (CV). The intermolecular noncovalent interactions in the crystal structures were assessed by density functional theory (DFT) calculations. The anticancer activity of Pd complexes in breast cancer cell lines was limited by their solubility. Pd(dpp-Bian) complexes with dmit and dsit ligands as well as an uncoordinated dpp-Bian ligand were devoid of cytotoxicity, while the [Pd(dpp-Bian)Cl2] complex was cytotoxic. On the contrary, all Pt(dpp-Bian) complexes demonstrated anticancer activity in a low micromolar concentration range, which was 8-20 times higher than the activity of cisplatin, and up to 2.5-fold selectivity toward cancer cells over healthy fibroblasts. The presence of a redox-active dpp-Bian ligand in Pt and Pd complexes resulted in the induction of reactive oxygen species (ROS) in cancer cells. In addition, these complexes were able to intercalate into DNA, indicating the dual mechanism of action.

AB - A series of heteroleptic square-planar Pt and Pd complexes with bis(diisopropylphenyl) iminoacenaphtene (dpp-Bian) and Cl, 1,3-dithia-2-thione-4,5-dithiolate (dmit), or 1,3-dithia-2-thione-4,5-diselenolate (dsit) ligands have been prepared and characterized by spectroscopic techniques, elemental analysis, X-ray diffraction analysis, and cyclic voltammetry (CV). The intermolecular noncovalent interactions in the crystal structures were assessed by density functional theory (DFT) calculations. The anticancer activity of Pd complexes in breast cancer cell lines was limited by their solubility. Pd(dpp-Bian) complexes with dmit and dsit ligands as well as an uncoordinated dpp-Bian ligand were devoid of cytotoxicity, while the [Pd(dpp-Bian)Cl2] complex was cytotoxic. On the contrary, all Pt(dpp-Bian) complexes demonstrated anticancer activity in a low micromolar concentration range, which was 8-20 times higher than the activity of cisplatin, and up to 2.5-fold selectivity toward cancer cells over healthy fibroblasts. The presence of a redox-active dpp-Bian ligand in Pt and Pd complexes resulted in the induction of reactive oxygen species (ROS) in cancer cells. In addition, these complexes were able to intercalate into DNA, indicating the dual mechanism of action.

KW - Cisplatin

UR - http://www.scopus.com/inward/record.url?scp=85123901225&partnerID=8YFLogxK

U2 - 10.1021/acs.inorgchem.1c03314

DO - 10.1021/acs.inorgchem.1c03314

M3 - Article

C2 - 35029379

AN - SCOPUS:85123901225

VL - 61

SP - 2105

EP - 2118

JO - Inorganic Chemistry

JF - Inorganic Chemistry

SN - 0020-1669

IS - 4

ER -

ID: 35393352