Synthesis and cellular uptake of neutral rhenium(i) morpholine complexes

Abstract

Morpholine motifs have been used extensively as targeting moieties for lysosomes, primarily in fluorescence imaging agents. Traditionally these imaging agents are based on organic molecules which have several shortcomings including...

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

“…Recent studies suggest that mammalian cells contain a variety of lysosome-like organelles, but their properties and functions are not well understood. 65 Commercial lysosomal markers 66 and investigational lysosomal probes, 67 including transition metal complexes, 13,64 usually contain tertiary amine groups that are protonated at pH 4.5–5.5, which leads to the probe entrapment within the acidic lysosomes. The use of non-amine based lysosomal probes, such as 1a , can be beneficial for targeting other properties of lysosomes and related organelles, such as polarity, 68 viscosity 69 and the production of strong oxidants (H 2 O 2 and HOCl).…”

“…The mode of action of 1a is likely to be different from that of traditional organic and metal-based probes that form positively charged species in the acidic environment of lysosomes. 13,64,67 A crucial advantage of 1a as an organelle probe is its potential use as a carbonyl tag for the studies of chemical content of organelles by vibrational spectroscopy, 15,16 as well as a Re tag for cell mapping by XFM. 17,18 Given the central role of lysosomes in cellular homeostasis, better understanding of their functions and dysfunctions is of great current interest in drug development for a variety of disorders, including cancer and neurodegenerative diseases.…”

“…17,18 Given the central role of lysosomes in cellular homeostasis, better understanding of their functions and dysfunctions is of great current interest in drug development for a variety of disorders, including cancer and neurodegenerative diseases. 65 Further development of neutral Re( i ) tricarbonyl complexes with thiolato ligands as multimodal probes for organelle targeting 3,13–17 is therefore warranted.…”

“…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…”