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

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

Journal

Inorganic Chemistry
ISSN: 0020-1669 , E-ISSN: 1520-510X

Output data

Year: 2022, Volume: 61, Number: 4, Pages: 2105-2118 Pages count : 14 DOI: 10.1021/acs.inorgchem.1c03314

Authors

Romashev Nikolai F. ¹ , Abramov Pavel A. ¹ , Bakaev Ivan V. ¹ , Fomenko Iakov S. ¹ , Samsonenko Denis G. ¹ , Novikov Alexander S. ² , Tong Kelvin K.H. ³ , Ahn Dohyun ³ , Dorovatovskii Pavel V. ⁴ , Zubavichus Yan V. ⁵ , Ryadun Aleksey A. ¹ , Patutina Olga A. ⁶ , Sokolov Maxim N. ¹ , Babak Maria V. ³ , Gushchin Artem L. ¹

Affiliations

1	Nikolaev Institute of Inorganic Chemistry SB RAS, 3 Acad. Lavrentiev Ave., Novosibirsk 630090, Russia
2	Institute of Chemistry, Saint Petersburg State University, Universitetskaya Nab., 7/9, Saint Petersburg 199034, Russia
3	Drug Discovery Lab, Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong SAR 999077, People’s Republic of China
4	National Research Center “Kurchatov Institute”, Kurchatov Square 1, Moscow 123182, Russia
5	Boreskov Institute of Catalysis, 5 Acad. Lavrentiev Ave., Novosibirsk 630090, Russia
6	Institute of Chemical Biology and Fundamental Medicine, 8 Acad. Lavrentiev Ave., Novosibirsk 630090, Russia

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.

Romashev N.F. , Abramov P.A. , Bakaev I.V. , Fomenko I.S. , Samsonenko D.G. , Novikov A.S. , Tong K.K.H. , Ahn D. , Dorovatovskii P.V. , Zubavichus Y.V. , Ryadun A.A. , Patutina O.A. , Sokolov M.N. , Babak M.V. , Gushchin A.L.
Heteroleptic Pd(II) and Pt(II) Complexes with Redox-Active Ligands: Synthesis, Structure, and Multimodal Anticancer Mechanism
Inorganic Chemistry. 2022. V.61. N4. P.2105-2118. DOI: 10.1021/acs.inorgchem.1c03314 WOS Scopus РИНЦ OpenAlex

Submitted:	Oct 25, 2021
Published online:	Jan 14, 2022

Web of science:	WOS:000744462900001
Scopus:	2-s2.0-85123901225
Elibrary:	48146829
OpenAlex:	W4205901008

DB	Citing
Web of science	30
Scopus	32
Elibrary	32
OpenAlex	35