Copper(II) Complexes with 2,2′:6′,2″-Terpyridine Derivatives Displaying Dimeric Dichloro−μ–Bridged Crystal Structure: Biological Activities from 2D and 3D Tumor Spheroids to In Vivo Models

Abstract

Eight 2,2′:6′,2″-terpyridines, substituted at the 4′position with aromatic groups featuring variations in π-conjugation, ring size, heteroatoms, and methoxy groups, were employed to enhance the antiproliferative potential of [Cu 2 Cl 2 (R-terpy) 2 ]-(PF 6 ) 2 . Assessing the cytotoxicity in A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), and HCT116DoxR (colorectal carcinoma resistant to doxorubicin) and normal primary fibroblasts revealed that Cu(II) complexes with 4-quinolinyl, 4-methoxy-1naphthyl, 2-furanyl, and 2-pyridynyl substituents showed superior therapeutic potential in HCT116DoxR cells with significantly reduced cytotoxicity in normal fibroblasts (42−129× lower). Besides their cytotoxicity, the Cu(II) complexes are able to increase intracellular ROS and interfere with cell cycle progression, leading to cell death by apoptosis and autophagy. Importantly, they demonstrated antimetastatic and antiangiogenic properties without in vivo toxicity. In accordance with their nuclear accumulation, the Cu(II) complexes are able to cleave pDNA and interact with bovine serum albumin, which is a good indication of their ability for internalization and transport toward tumor cells.

Isosteric Replacement of Sulfur to Selenium in a Thiosemicarbazone: Promotion of Zn(II) Complex Dissociation and Transmetalation to Augment Anticancer Efficacy

“…The excess ligand that dissociates from [Zn­(PPTP4c4mSe)­Cl] 2 may drive formation of the 2:1 L:Cu­(II) complex upon the addition of Cu­(OAc) 2 (Figures S6A–D and S7). This facile dissociation may occur due to the dichlorido bridge in [Zn­(PPTP4c4mSe)­Cl] 2 (Figure B) being readily hydrolyzed, as demonstrated for other complexes of this type. − …”

Synthesis, X-ray Studies and Photophysical Properties of Iridium(III) Complexes Incorporating Functionalized 2,2′:6′,2″ Terpyridines and 2,6-Bis(thiazol-2-yl)pyridines

“…The main aim of this work was to explore the impact of the triimine skeleton (terpy and dtpy) and substituents (thiophene, bithiophene, and EDOT) on the photophysical properties of Ir(III) complexes. Recently, some efforts have been made to understand the structure-property correlation in rhenium(I), platinum(I), gold(I), cobalt(II), and copper(II) [20][21][22][23][24][25][26] complexes by introducing the R substituent in the 4 ′ -position of the terpy and/or dtpy rings. However, to the best of our knowledge, [IrCl 3 (L)] complexes incorporating terpy (ligands L 1 -L 3 ) and dtpy derivatives (ligands L 4 -L 6 ) are quite rare and will be reported here for the first time (see Table S15).…”