Synthesis of Rhenium(I) Tricarbonyl Complexes with Carbohydrate‐Pendant Tridentate Ligands and Their Cellular Uptake

Abstract

Abstract Twelve [Re I L (CO) 3 ] n + complexes with various carbohydrate‐pendant ligands L have been prepared and their uptake into HeLa S3 cells were investigated. The ligand library includes: (i) glucose/galactose as the carbohydrate group; (ii) bis(2‐pyridylmethyl)amine (DPA), bis(2‐quinolylmethyl)amine (DQA), or N ‐(2‐pyridylmethyl)glycine (NPG) as the metal binding component; and (iii) an ethylene chain as a linker between the metal binding site and the O / C ‐glycosides. Microwave induced plasma mass spectroscopy (MIP‐MS) measurements revealed that all complexes were extensively incorporated into the HeLa cells over a 24 h period, and the DQA complexes showed the highest uptake of all the complexes in the series. However, in comparison to the corresponding Re complexes without the pendant carbohydrate functions (prepared with the related ligands L DPA , L DQA , and L NPG ), only the NPG complexes exhibited carbohydrate enhanced cellular uptake. Considering their water solubility and cellular uptake properties, the NPG complexes containing an O ‐glycoside group ( L1 and L′1 ) are the best candidates for enhancing cellular uptake of metal ions. Microscopic analysis with PC‐12 cells in the presence of thefluorescent complex [Re( L′7 )(CO) 3 ]Cl, revealed that the complex stays in the cell cytosol and cannot penetrate into the nucleus.