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

Abstract

Three new cobalt-ruthenium heterometallic molecular rectangles, 1-3, were synthesized through the coordination-driven self-assembly of a new cobalt sandwich donor, (η -Cp)Co[C -trans-Ph (4-Py) ] (L; Cp: cyclopentyl; Py: pyridine), and one of three dinuclear precursors, [(p-cymene) Ru (OO∩OO) Cl ] [OO∩OO: oxalato (A ), 5,8-dioxido-1,4-naphthoquinone (A ), or 6,11-dioxido-5,12-naphthacenedione (A )]. 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.

Heterometallic Multinuclear Complexes as Anti‐Cancer Agents‐An Overview of Recent Developments

“…The stability of these complexes was also confirmed with 1 H NMR. No dissociation was observed in the presence of DMSO over 48 hours …”

“…Chi and colleagues reported a series of multinuclear ruthenium‐cobalt rectangles with potent anti‐cancer activity. Similar to the previously discussed Pt‐Ru metalla‐rectangles by the same research group (Figure ), the Co‐Ru metalla‐rectangles contained a rigid Co II dipyridyl donor, ((η 5 ‐Cp)Co[C 4 ‐ trans ‐Ph 2 (4‐Py) 2 ] where Cp refers to cyclopentadienyl and Py to pyridine) and varying Ru‐arene acceptors (Figure ) …”

“…The coordination‐driven self‐assembled ruthenium‐cobalt heterometallic rectangles investigated by Chi and colleagues . The IC 50 (µM) values reported are shown below the chemical structures.…”

The First-Row Transition Metals in the Periodic Table of Medicine

“…Anticancer activity has been observed in a number of Co(II) and Co(III) Schiff base complexes [127,129]. Dinuclear heterometallic Co compounds have also been investigated, such as a cobalt-ruthenium cobaltocene derivatives which showed increased autophagic activity relative to the mononuclear Co derivative [130,131]. In addition, the radioisotope 60 Co has been used as a source of high-energy radiation to destroy cancerous tissue [132].…”

Recent Progress of Discrete Metallacycles Based on the Half-Sandwich Ir/Rh/Ru Motifs

“…金国新等 [41] 先用三联吡啶与二价铜、锌、镍等 金属配位形成双配位点的吡啶基配体(L9), 然后与双金 属铑、铱分子夹(E)通过[2＋2]自组装构建四核异金属矩 形框架配合物(图 6). 2016 年, Chi 课题组 [42] 基于具有三 明治结构的钴配合物开发含氮双齿配体(L10), 与草酸 类衍生物(A)和半夹心金属钌自组装构建四核异金属矩 形框架配合物. 得益于金属钴和钌都有很好的生物抗癌 活性, 这些包含双金属的框架化合物对胃癌细胞具有高 的细胞毒性, 能够诱导胃癌细胞自噬凋亡, 为抗胃癌药 物的开发提供了新的思路(图 7).…”