Effects of Bis(imino)acenaphthene (Bian)-Derived Ligands on the Cytotoxicity, DNA Interactions, and Redox Activity of Palladium(II) Bipyridine Complexes

Abstract

A series of heteroleptic bipyridine Pd­(II) complexes based on 1,2-bis­[(2,6-diisopropylphenyl)­imino]­acenaphthene (dpp-Bian) or 1,2-bis­[(2,4,6-trimethylphenyl)­imino]­acenaphthene (tmp-Bian) were prepared. All complexes were fully characterized by spectrochemical methods, and their crystal structures were confirmed by X-ray diffraction analysis. The 72 h stability of heteroleptic bipyridine Pd­(II) complexes with Bian ligands under physiological conditions was investigated using 1H NMR spectroscopy. The anticancer activity of all complexes was assessed in a panel of cancer cell lines in comparison with uncoordinated ligands and clinically used drugs cisplatin and doxorubicin. The ability of the complexes to bind DNA was investigated using several methods, including EtBr replacement assay, density functional theory calculations, circular dichroism spectroscopy, DNA gel electrophoresis, and TUNEL assay. The electrochemical activity of all complexes and the uncoordinated ligands was studied using cyclic voltammetry, and reactive oxygen species production in cancer cells was investigated using confocal microscopy. Heteroleptic bipyridine PdII-Bian complexes were cytotoxic in a low micromolar concentration range and showed some selectivity toward cancer cells in comparison with noncancerous MRC-5 lung fibroblasts.

Gold(i) complexes with redox active BIAN and MIAN ligands: synthesis, structure and electrochemistry

“…Previously it was reported that uncoordinated BIAN ligands, including dpp-bian, did not display biological activity due to poor solubility in biological media. 20,21 Herein, we also observed that dpp-bian and dpp-mian ligand were not characterized by any cytotoxicity in all tested cell lines. However, substitution of bulky dpp fragments with methyl groups in 2-Me-Ph-bian or 4-Me-Ph-bian resulted in the considerable improvement of their solubility in DMSO and, as a consequence, the increase of their cytotoxicity.…”

“…We developed a series of heteroleptic complexes of palladium and platinum with dpp-bian and tmp-bian ligands, which demonstrated anticancer activity in the range of low micromolar concentrations. 20,21 It should be noted that the distribution of studies on metal complexes with BIAN ligands is extremely uneven. While there are many studies on the complexes of main group elements and 3d metals, the data available for BIAN complexes of 4d and especially 5d metals are limited.…”

“…We developed a series of heteroleptic complexes of palladium and platinum with dpp-bian and tmp-bian ligands, which demonstrated anticancer activity in the range of low micromolar concentrations. 20,21…”

Mono(arylhydrazino)acenaphthenones as a platform for the design of NIR chromophores based on Pd(ii)-BIAN complexes

“…8,9 The Pd-N bond lengths are 2.01-2.10 Å, which is in the standard range of values for palladium diimine complexes. 30,31,56 Crystal packings of 3 and 4 are similar (Fig. S15, ESI †).…”

“…For cations of 3-5, HOMOs are almost completely localized on the acenaphthenehydrazone fragment, while LUMOs are localized on Ar-bian, which is typical for square planar Pd/Ar-bian complexes. 30,31 The composition of frontier orbitals is presented in Table S2 (ESI †).…”