Abstract
Two new neutral fac-[Re(CO)3(phen)L] compounds (1,2), with phen = 1,10-phenanthroline and L = O2C(CH2)5CH3 or O2C(CH2)4C≡CH, were synthetized in one-pot procedures from fac-[Re(CO)3(phen)Cl] and the corresponding carboxylic acids, and were fully characterized by IR and UV-Vis absorption spectroscopy, 1H- and 13C-NMR, mass spectrometry and X-ray crystallography. The compounds, which display orange luminescence, were used as probes for living cancer HeLa cell staining. Confocal microscopy revealed accumulation of both dyes in mitochondria. To investigate the mechanism of mitochondrial staining, a new non-emissive compound, fac-[Re(CO)3(phen)L], with L = O2C(CH2)3((C5H5)Fe(C5H4), i.e., containing a ferrocenyl moiety, was synthetized and characterized (3). 3 shows the same mitochondrial accumulation pattern as 1 and 2. Emission of 3 can only be possible when ferrocene-containing ligand dissociates from the metal center to produce a species containing the luminescent fac[Re(CO)3(phen)]+ core. The release of ligands from the Re center was verified in vitro through the conjugation with model proteins. These findings suggest that the mitochondria accumulation of compounds 1–3 is due to the formation of luminescent fac-[Re(CO)3(phen)]+ products, which react with cellular matrix molecules giving secondary products and are uptaken into the negatively charged mitochondrial membranes. Thus, reported compounds feature a rare dissociation-driven mechanism of action with great potential for biological applications.
Highlights
Results and Discussion proteins enables us to propose a mechanism explaining the molecular basis of the mitochondrial accumulation of 1–3
We found that the fac-[Re(CO)3(phen)Cl] complex [44] readily reacts with carboxylic acids in THF in the presence of trimethylamine and silver trifluoromethanesulfonate at 70 °C to afford
In order to evaluate if the synthetized compounds coordinate to biological macromolecules in particular proteins, and to check if the degradation of compound 3 is the result of these interactions, particular proteins, and to check if the degradation of compound 3 is the result of these interactions, we have studied the formation of potential adducts that could form upon reaction of compounds 1 we have studied the formation of potential adducts that could form upon reaction of compounds 1 or 3 or 3 with model proteins hen egg white lysozyme (HEWL) and bovine pancreatic ribonuclease with model proteins hen egg white lysozyme (HEWL) and bovine pancreatic ribonuclease (RNase A), (RNase A), which have been extensively used in the past in metalation studies [51,52,53]
Summary
Luminescent transition metal complexes have been extensively used in organic light-emitting light-emitting diodes (OLEDs). Most of the research has been focused on cationic complexes (classes A and B in Figure 1) which preferably stain mitochondria [20,21,22,23]. Relevant examples of such compounds comprise cationic A1 [20]. Dirhenium piridazine complex C1 stain the cytoplasm and nucleus [25], and compounds D1–3 stain the perinuclear region of MDA-MB-231 cells [24]. Nucleus [25], and compounds D1–3 stain the perinuclear region of MDA-MB-231 cells [24] Results and Discussion proteins enables us to propose a mechanism explaining the molecular basis of the mitochondrial accumulation of 1–3
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