Self-assembled metalla-rectangles bearing azodipyridyl ligands: synthesis, characterization and antitumor activity

Abstract

Sixteen arene-Ru based molecular-rectangles were self-assembled in high yields by the equimolar mixing of arene-Ru acceptors (Aa-Ad) with various azopyridyl ligands (1,2-di(pyridyl-4yl)diazene (L1), 1,2-bis(pyridin-4-ylmethylene)hydrazine (L2), 1,2-bis(1-(pyridin-4-yl)ethylidene)hydrazine (L3), 1,2-bis(pyridin-4-ylmethylene)hydrazine (L4)) in nitromethane-methanol solutions. These new molecular-rectangles were fully characterized by a host of analytical techniques including elemental analysis, (1)H and (13)C NMR and HR-ESI-MS. The solid-state structures of two molecular-rectangles (1b and 4d) were determined by single crystal X-ray diffraction data. UV-visible and fluorescence studies were also carried out for the entire suite of rectangles. As with recent studies of similar arene-Ru complexes, the anti-proliferative activities of these complexes were evaluated against SK-hep-1 (liver cancer) and A-549 (lung cancer) human cancer lines. Additionally, the cellular pharmacology and intracellular localizations in AGS (gastric cancer) human cancer cells were determined for selected complexes (1c, 1d and 4c) by apoptosis and fluorescence microscopy studies. These studies confirm that arene-Ru molecular-rectangles inhibit cell cycle progression to the G0 phase, in contrast to that of cisplatin which arrests cell growth in the G2 phase.

Biomedical and Biochemical Applications of Self-Assembled Metallacycles and Metallacages

“…The IC 50 values of the corresponding clips were significantly higher, with only the donq clip showing measurable activity for SK-hep-1 cells. 23 The donq-based SCCs were particularly potent, with IC 50 values oftentimes exceeding that of cisplatin, and on par with a second control drug, doxorubicin. The oxalato and dobq-containing species were relatively inactive in comparison.…”

“…For example, by incorporating amide groups into the core of dipyridyl donors, 17 and 18 , 25 sites for hydrogen bonding were preserved and the presence of azo functionalities on donors 19 – 22 unlock potential photo-sensitization. 23 The assemblies formed from the combinations of 17 – 22 with 6 – 9 were investigated using five cell lines obtained from American Type Culture Collection for SCC25-SCC27 : HeLa, HCT-15, and MDA-MB-231, SK-hep-1, A-549, with the latter two cell lines also used in assays with the sixteen azodipyridyl-based assemblies. SCC25 and SCC26 , containing the oxalate bridged clip, were inactive, while rectangle SCC27 , which employed the donq-bridged clip, possessed IC 50 values that were similar to those of cisplatin, with values (µM) of 4.2 ± 0.11 (SK-hep-1); 10.2 ± 0.21 (HeLa); 3.7 ± 0.10 (HCT-15); 3.2± 0.11(A-549); 2.8 ± 0.03 (MDA-MB-231).…”

The Biological Side of Water-Soluble Arene Ruthenium Assemblies

“…Following these first studies, Chi, Stang and coworkers have reported several analogous metalla-rectangles, each being formed by combining dinuclear arene ruthenium clips and bipyridyl connectors [39,[61][62][63][64][65]. The IC 50 values for particular combinations of clips and connectors are in the lower micromolar range, while others show poor activities.…”

Growth Inhibitory Activity of a Bis-Benzimidazole-Bridged Arene Ruthenium Metalla-Rectangle and -Prism

“…3 Recently, a variety of arene-Ru molecular clips bridged by O,O-chelating ligands have been reported for the self-assembly of metalla-rectangles and prisms. 4 In this context, ruthenium is not simply a structural element; the metal fulfils a functional role as the impetus for antitumor activity. 5 …”