Self‐Assembly of Ambidentate Pyridyl‐Carboxylate Ligands with Octahedral Ruthenium Metal Centers: Self‐Selection for a Single‐Linkage Isomer and Anticancer‐Potency Studies

Abstract

The synthesis of six new [2+2] metallarectangles through the coordination-driven self-assembly of octahedral Ru(II)-based acceptors with ambidentate pyridyl-carboxylate donors is described. These molecular rectangles are fully characterized by (1)H NMR spectroscopy, high-resolution electrospray mass spectrometry, and single-crystal X-ray diffraction. In each case, despite the possible formation of multiple isomers, based on the relative orientation of the pyridyl and carboxylate groups (head-to-head versus head-to-tail), evidence for the formation of a single preferred ensemble (head-to-tail) was found in the (1)H NMR spectra. Furthermore, the cytotoxicities of all of the rectangles were established against A549 (lung), AGS (gastric), HCT-15 (colon), and SK hep 1 (liver) human cancer cell lines. The cytotoxicities of rectangles that contained the 5,8-dihydroxy-1,4-naphthaquinonato bridging moiety between the Ru centers (9-11) were particularly high against AGS cancer cells, with IC50 values that were comparable to that of reference drug cisplatin.

Investigation of the biological and anti-cancer properties of ellagic acid-encapsulated nano-sized metalla-cages

“…56 We measured the effect of ellagic acid and compound 10 on the secretion of 23 cytokines by using macrophages, with an enzyme-linked immunosorbent assay (ELISA) array chosen to represent cytokines, which are known to inhibit the growth of tumor cells. As shown in Figure 6, compound 10 stimulated G-CSF by 18.4% compared to control cells. G-CSF decreases the morbidity of cancer chemotherapy by reducing the incidence of febrile neutropenia.…”

“…[10][11][12][13][14][15][16][17][18][19] Three-dimensional cages, engineered via coordinationdriven self-assembly paradigms, have distinct advantages over conventional covalentcontainer molecules, owing to the synthetic ease with which the coordination cages can be assembled, the availability of a large library of building blocks, and the ability to design selective guest encapsulations. 20,21 The strong and highly directional nature of metal-ligand interactions results in the formation of stable and rigid coordination…”

“…[16][17][18][19] Furthermore, the physicochemical properties of the host-guest complex are generally superior to those of the guest alone, resulting in improved efficacy and biocompatibility. 22,23 The most widely used metal-based anticancer drug, cisplatin, [24][25][26] has been encapsulated in various hosts to reduce the severe side effects associated with this treatment.…”

Conformational control of anticancer activity: the application of arene-linked dinuclear ruthenium(ii) organometallics

“…7 Ru(II)-arene complexes have also been incorporated into multinuclear systems and assessed for their anticancer activity. These have included metalla-cycles, [8][9][10][11][12] metalla-cages [13][14][15] and dendrimer-based systems. 16 Of particular interest to us are the [Ru(h 6 -arene)Cl 2 (PTA)] (RAPTA) series of organometallic ruthenium(II) compounds which display selective activity on metastatic tumours in vivo.…”

Synthesis, Molecular Structure and Cytotoxicity of Molecular Materials Based on Water Soluble Half-Sandwich Rh(III) and Ir(III) Tetranuclear Metalla-Cycles

“…The tetranuclear assemblies have been found to possess good anticancer activity [7,8,9,10,11,12], to strongly interact with DNA [13,14], and to efficiently detect biologically relevant analytes [15,16,17]. Their DNA binding can occur through non-covalent interactions, novel modes of action also observed for di- and trinuclear organometallics [18,19,20], although fragmentation inside cells followed by coordination of the metal ion to DNA and/or other biomolecules cannot be excluded.…”