Light‐Activated Carbon Monoxide Prodrugs Based on Bipyridyl Dicarbonyl Ruthenium(II) Complexes

Abstract

Two photoactivatable dicarbonyl ruthenium(II) complexes based on an amide‐functionalised bipyridine scaffold (4‐position) equipped with an alkyne functionality or a green‐fluorescent BODIPY (boron‐dipyrromethene) dye have been prepared and used to investigate their light‐induced decarbonylation. UV/Vis, FTIR and 13C NMR spectroscopies as well as gas chromatography and multivariate curve resolution alternating least‐squares analysis (MCR‐ALS) were used to elucidate the mechanism of the decarbonylation process. Release of the first CO molecule occurs very quickly, while release of the second CO molecule proceeds more slowly. In vitro studies using two cell lines A431 (human squamous carcinoma) and HEK293 (human embryonic kidney cells) have been carried out in order to characterise the anti‐proliferative and anti‐apoptotic activities. The BODIPY‐labelled compound allows for monitoring the cellular uptake, showing fast internalisation kinetics and accumulation at the endoplasmic reticulum and mitochondria.

Intracellular Localization Studies of the Luminescent Analogue of an Anticancer Ruthenium Iminophosphorane with High Efficacy in a Triple-Negative Breast Cancer Mouse Model

“…Ruthenium compounds have shown varied preferential localization in different cellular compartments and organelles, mostly in nuclear, lysosomal, and mitochondrial compartments. Intracellular localization studies with ruthenium compounds that incorporate BODIPY ligands in their structure have been reported, ,− as well as studies to assess cellular uptake . Ruthenium­(II) p -cymene compounds with chelating O,O and N,O ligands containing BODIPY have accumulated preferentially in mitochondria, while with pyridine and bipyridyl BODIPY-modified ligands, accumulation in both mitochondria and the endoplasmic reticulum was observed.…”

“…Intracellular localization studies with ruthenium compounds that incorporate BODIPY ligands in their structure have been reported, ,− as well as studies to assess cellular uptake . Ruthenium­(II) p -cymene compounds with chelating O,O and N,O ligands containing BODIPY have accumulated preferentially in mitochondria, while with pyridine and bipyridyl BODIPY-modified ligands, accumulation in both mitochondria and the endoplasmic reticulum was observed. Metallorectangles based on ruthenium­(II) p -cymene derivatives with BODIPY-modified polypyridyl ligands were shown to have different preferential accumulation in cellular compartments depending on the type of cancer cell line .…”

Bioorthogonal Reactions of Triarylphosphines and Related Analogues

“…The high chemoselectivity of the reaction permits its use in the presence of native, unprotected biomolecules. In one example, the traceless Staudinger ligation was used to attach position emission tomography (PET) tags to small molecules. , Phosphines comprising radioactive 18 F- or 131 I-labeled acyl chains were incubated with azide-bearing pharmaceutical agents. ,− The PET-tagged products could be used immediately for in vivo imaging. The products did not require purification owing to the mild nature of the ligation and lack of toxic byproducts.…”

Switching on Cytotoxicity of Water-Soluble Diiron Organometallics by UV Irradiation

“…Besides, the photoinduced release of carbon monoxide has been intensively studied in the last two decades due to the therapeutic effects provided by this small molecule in low concentrations, and many different metal-based photoactivable CO-releasing molecules (photoCORM) have been studied in biological settings. , Interestingly, some Mn­(I), Re­(I), and Ru­(II) complexes manifested photoinduced antiproliferative activity on cancer cells or antimicrobial activity upon exposure to UV (305–365 nm) , or visible (>440 nm) light for a relatively short time (typically 10–15 or 30–45 min, respectively). These biological effects have been often associated with the intracellular release of CO, although the role of the metal fragment deserves consideration. , …”