Rhenium fac-Tricarbonyl Bisimine Chalcogenide Complexes: Synthesis, Photophysical Studies, and Confocal and Time-Resolved Cell Microscopy

Abstract

We describe the preparation, characterization, and imaging studies of rhenium carbonyl complexes with a pyta (4-(2-pyridyl)-1,2,3triazole) or tapy (1-(2-pyridyl)-1,2,3-triazole)-based heteroaromatic N∧N ligand and thiolate or selenoate X ligand. The stability and photophysical properties of the selenolate complexes are compared with parent chloride complexes and previously described analogues with benzenethiolate ligands. Two complexes were imaged in A549 cells upon excitation at 405 nm. Colocalization studies suggest a lysosomal accumulation, while one parent chloride complex was described to localize at the Golgi apparatus. Preliminary fluorescence lifetime measurements and imaging demonstrate potential for application in time-resolved microscopy techniques due to the long and variable lifetimes observed in cellular environments, including an increase in lifetime between the solution and solid state many times larger than previously reported.

Neutral rhenium(i) tricarbonyl complexes with sulfur-donor ligands: anti-proliferative activity and cellular localization

“…Predominantly lysosomal localization is often observed for Re(CO) 3 and other lipophilic metal complexes, which is generally regarded as a part of cell protection from toxic compounds. 14,64 However, Fig. 12a shows that the distribution of 1a in the lysosomal region of the cells was distinctly different from that of the Lysotracker dye, with 1a staining a smaller subset of mostly well-separated lysosome-like particles.…”

“…Their utility arises from their synthetic versatility and favourable photophysical properties (large Stokes shift and high photostability) of such complexes. 3,5,7,11–14 Importantly, fac -[Re(NN)(CO) 3 L] +/0 complexes are uniquely suitable for multimodal biological imaging, 15 including phosphorescence measurements, infrared and Raman spectroscopic mapping (CO tag) and X-ray fluorescence microscopy (XFM) mapping of Re and other heavy elements (such as I-substituted ligands). 3,16–20…”

“…A vast majority of biologically active Re( i ) complexes contain N-donor axial ligands, 2–4,12 while the use of S-donor ligands is uncommon. 14,30 Lipophilic thiolato ligands can facilitate rapid cellular uptake of the complexes and minimize decomposition in the extracellular medium. 14,31 In addition, most of the known biologically active Re( i ) complexes are cationic 2–4 and tend to target mitochondria, 26,29,32 so the use of neutral thiolato complexes can provide an alternate mechanism of action.…”

“…14,30 Lipophilic thiolato ligands can facilitate rapid cellular uptake of the complexes and minimize decomposition in the extracellular medium. 14,31 In addition, most of the known biologically active Re( i ) complexes are cationic 2–4 and tend to target mitochondria, 26,29,32 so the use of neutral thiolato complexes can provide an alternate mechanism of action. 12,14 Recently, we have shown that some dimeric Ru( ii )-arene complexes with thiocarboxylato ligands were selectively cytotoxic in an invasive triple-negative mesenchymal-like human breast cancer cell line, MDA-MB-231, over a panel of non-invasive epithelial cancer cell lines.…”

“…14,31 In addition, most of the known biologically active Re( i ) complexes are cationic 2–4 and tend to target mitochondria, 26,29,32 so the use of neutral thiolato complexes can provide an alternate mechanism of action. 12,14 Recently, we have shown that some dimeric Ru( ii )-arene complexes with thiocarboxylato ligands were selectively cytotoxic in an invasive triple-negative mesenchymal-like human breast cancer cell line, MDA-MB-231, over a panel of non-invasive epithelial cancer cell lines. 33 In this work, methyl esters of these acid ligands (methyl-mercaptocarboxylic esters) being nominally bifunctional but designed to be constrained as monodentate at the S atom were synthesized and characterised.…”