Strategy to Optimize the Biological Activity of Arene Ruthenium Metalla-Assemblies

Three new dinuclear arene ruthenium metalla-clips of the general formula [(<i>p</i>-cymene)₂­Ru₂Cl₂­(μ-L)] have been prepared from [(<i>p</i>-cymene)₂­Ru₂Cl₂­(μ-Cl)₂] and H₂L organic linkers (H₂L^a = diethyl-1,2-diazenedicarboxylate, H₂L^b = <i>N</i>,<i>N′</i>-bis­(2-hydroxy­ethyl)­oxamide, H₂L^c = <i>N</i>,<i>N′</i>-bis­{2-(2-hydroxy­ethoxy)­ethyl}­ethanediamide). The bis-chelating bridging-linkers possess two functional groups that can be synthetically modified for physico-chemical optimizations. Reaction of these three dinuclear metalla-clips with 4,4′-bipyridine, 1,2-bis­(4-pyridyl)­ethylene, and 4,4′-azopyridine affords, in the presence of AgCF₃SO_3, nine tetracationic tetranuclear metalla-rectangles. Similarly, the tridentate ligands 2,4,6-tris­(4-pyridyl)-1,3,5-triazine and 1,3,5-tris­{2-(4-pyridyl)­vinyl}­benzene were used to generate six hexacationic hexanuclear metalla-prisms. All metalla-assemblies and the dinuclear complexes were evaluated as anticancer agents against cancerous (A2780) and noncancerous (HEK293) cell lines, showing an excellent selectivity for cancer cells. The IC₅₀ values of the cationic metalla-assemblies were typically <1 μM, whereas, for the neutral dinuclear metalla-clips, the IC₅₀ values were >100 μM

Electron-Rich Arene–Ruthenium Metalla-architectures Incorporating Tetrapyridyl–Tetrathiafulvene Donor Moieties

A series of arene ruthenium architectures have been prepared from coordination-driven self-assembly using dinuclear <i>p</i>-cymene ruthenium acceptors and π-donating tetratopic tetrapyridyl–tetrathiafulvalene donor ligands. The synthetic strategy, based on a geometric interaction approach, leads to four electroactive metalla-assemblies, <b>1</b>–<b>4</b> (one molecular cube and three metallaplates), that were characterized by NMR, ESI-MS, X-ray diffraction, and cyclic voltammetry. Rationalization of their formation discrepancy was completed by DFT calculations supported by structural features of their constituting TTF and Ru-complex components. Metalla-architectures possessing electron-rich cores (<b>3</b>, <i>cis-</i><b>4</b>, and <i>trans</i>-<b>4</b>) interact strongly with picric acid (PA) to yield cocrystallized products, PA + metalla-assemblies, confirmed by single-crystal X-ray structure analyses

Efficient and Rapid Mechanochemical Assembly of Platinum(II) Squares for Guanine Quadruplex Targeting

We present a rapid and efficient method to generate a family of platinum supramolecular square complexes, including previously inaccessible targets, through the use of ball milling mechanochemistry. This one-pot, two-step process occurs in minutes and enables the synthesis of the squares [Pt₄(en)₄(N∩N)₄]­[CF₃SO₃]₈ (en= ethylenediamine, N∩N = 4,4′-bipyridine derivatives) from commercially available precursor K₂PtCl₄ in good to excellent yields. In contrast, solution-based assembly requires heating the reagents for weeks and gives lower yields. Mechanistic investigations into this remarkable rate acceleration revealed that solution-based assembly (refluxing for days) results in the formation of large oligomeric side-products that are difficult to break down into the desired squares. On the other hand, ball milling in the solid state is rapid and appears to involve smaller intermediates. We examined the binding of the new supramolecular squares to guanine quadruplexes, including oncogene and telomere-associated DNA and RNA sequences. Sub-micromolar binding affinities were obtained by fluorescence displacement assays (FID) and isothermal titration calorimetry (ITC), with binding preference to telomere RNA (TERRA) sequences. ITC showed a 1:1 binding stoichiometry of the metallosquare to TERRA, while the stoichiometry was more complex for telomeric quadruplex DNA and a double-stranded DNA control

Divinylanthracene-Containing Tetracationic Organic Cyclophane with Near-Infrared Photoluminescence

Near-infrared (NIR) light is known to have outstanding optical penetration in biological tissues and to be non-invasive to cells compared with visible light. These characteristics make NIR-specific light optimal for numerous biological applications, such as the sensing of biomolecules or in theranostics. Over the years, significant progress has been achieved in the synthesis of fluorescent cyclophanes for sensing, bioimaging, and making optoelectronic materials. The preparation of NIR-emissive porphyrin-free cyclophanes is, however, still challenging. In an attempt for fluorescence emissions to reach into the NIR spectral region, employing organic tetracationic cyclophanes, we have inserted two 9,10-divinylanthracene units between two of the pyridinium units in cyclobis(paraquat-p-phenylene). Steady-state absorption, fluorescence, and transient-absorption spectroscopies reveal the deep-red and NIR photoluminescence of this cyclophane. This tetracationic cyclophane is highly soluble in water and has been employed successfully as a probe for live-cell imaging in a breast cancer cell line (MCF-7)