Coordination-Driven Self-Assembly and Anticancer Potency Studies of Ruthenium-Cobalt-Based Heterometallic Rectangles

• Published in: Chemistry : a European journal Vol. 22; no. 45; pp. 16157 - 16164
• Main Authors: Singh, Nem, Jang, Sunphil, Jo, Jae-Ho, Kim, Dong Hwan, Park, Dae Won, Kim, InHye, Kim, Hyunuk, Kang, Se Chan, Chi, Ki-Whan
• Format: Journal Article
• Language: English
• Published: Germany Blackwell Publishing Ltd 02.11.2016; Wiley Subscription Services, Inc
• Subjects: Anticancer properties; antitumor agents; Apoptosis; Assaying; Autophagy; Bimetals; Cancer; Caspase; Caspase-3; Cell death; Chemical synthesis; Chemistry; Cobalt; Conversion; Crystal structure; Cytotoxicity; Doxorubicin; Gastric cancer; metallacycles; Mortality; p-Cymene; Phagocytosis; Pyridines; Rectangles; Ruthenium; Self assembly; Single crystals; Spectroscopic analysis; Toxicity; Western blotting; X-ray diffraction; ruthenium; self-assembly; cobalt; antitumor agents; metallacycles
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201603521

Three new cobalt–ruthenium heterometallic molecular rectangles, 1–3, were synthesized through the coordination‐driven self‐assembly of a new cobalt sandwich donor, (η5‐Cp)Co[C4‐trans‐Ph2(4‐Py)2] (L; Cp: cyclopentyl; Py: pyridine), and one of three dinuclear precursors, [(p‐cymene)2Ru2(OO∩OO)2Cl2] [OO∩OO: oxalato (A1), 5,8‐dioxido‐1,4‐naphthoquinone (A2), or 6,11‐dioxido‐5,12‐naphthacenedione (A3)]. All of the self‐assembled architectures were isolated in very good yield (92–94 %) and were fully characterized by spectroscopic analysis; the molecular structures of 2 and 3 were determined by single‐crystal X‐ray diffraction analysis. The anticancer activities of bimetallic rectangles 1–3 were evaluated with a 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide (MTT) assay, an autophagy assay, and Western blotting. Rectangles 1–3 showed higher cytotoxicity than doxorubicin in AGS human gastric carcinoma cells. In addition, the autophagic activities and apoptotic cell death ratios were increased in AGS cells by treatment with 1–3; the rectangles induced autophagosome formation by promoting LC3‐I to LC3‐II conversion and apoptotic cell death by increasing caspase‐3/7 activity. Our results suggest that rectangles 1–3 induce gastric cancer cell death by modulating autophagy and apoptosis and that they have potential use as agents for the treatment of human gastric cancer. Cytotoxic rectangles: The cytotoxic efficiencies of Co–Ru bimetallic molecular rectangles obtained by coordination‐driven self‐assembly of a cobalt sandwich‐based donor and RuII p‐cymene acceptors were evaluated. The study found the metallacycles to be potential candidates to induce apoptosis and autophagy in human cancer cells.