Structural and\nSolution Speciation Studies on <i>fac</i>-Tricarbonylrhenium(I)\nComplexes of 2,2′-Bipyridine\nAnalogues

In this study, we\nreport the synthesis and characterization of\n12 novel rhenium(I) complexes with the general formula <i>fac</i>-[Re(CO)<sub>3</sub>(NN)X]<sup>n+</sup> where (NN) is a 2,2′-bipyridine\nanalogue ligand, X = Cl<sup>–</sup>, Br<sup>–</sup>,\nor H<sub>2</sub>O, and <i>n</i> = 0 or 1, focusing on their\nspeciation in an aqueous solution. The prepared organorhenium complexes\nare stable in a wide pH range in an aqueous solution, and no release\nof the bidentate ligands or the carbonyl ligands was observed. The\nstability of the complexes in various biologically relevant matrices\n(cell culture medium and real blood serum) was also demonstrated.\nHowever, the simultaneous substitution of the halido ligand by water\nand slow hydrolysis of the ester bonds in the ligands were observed,\naffecting both the solubility and the lipophilicity of the compounds.\nThe aqua complexes became more lipophilic in the presence of chloride\nions, while the hydrophilicity increased significantly with time due\nto the hydrolysis of the ester bonds, which probably contributed to\ntheir weak pharmacological activity. The results also showed kinetically\nhindered aqueous solvation of the halido complexes and low chloride\nion affinity of the aqua complexes. The deprotonation of the coordinated\naqua ligand in the complexes occurs in the pH = 7–10 range,\nleading to significant formation (18–30%) of hydroxido species\nat pH = 7.4. The halido complexes showed somewhat higher cytotoxicity\n(IC<sub>50</sub> = 60–99 μM) on human colon adenocarcinoma\ncancer cells (Colo205 and Colo320) than the corresponding aqua complexes\n(IC<sub>50</sub> > 100 μM). In all cases, no antibacterial\neffect\nwas observed (MIC > 100 μM), but some of the complexes showed\nmoderate antiviral activity (IC<sub>50</sub> ∼ 50 μM)\non Herpes simplex virus 2.