Structural and Solution Speciation Studies on <i>fac</i>-Tricarbonylrhenium(I) Complexes of 2,2′-Bipyridine Analogues

In this study, we report the synthesis and characterization of 12 novel rhenium(I) complexes with the general formula <i>fac</i>-[Re(CO)₃(NN)X]ⁿ⁺ where (NN) is a 2,2'-bipyridine analogue ligand, X = Cl^-, Br^-, or H₂O, and <i>n</i> = 0 or 1, focusing on their speciation in an aqueous solution. The prepared organorhenium complexes are stable in a wide pH range in an aqueous solution, and no release of the bidentate ligands or the carbonyl ligands was observed. The stability of the complexes in various biologically relevant matrices (cell culture medium and real blood serum) was also demonstrated. However, the simultaneous substitution of the halido ligand by water and slow hydrolysis of the ester bonds in the ligands were observed, affecting both the solubility and the lipophilicity of the compounds. The aqua complexes became more lipophilic in the presence of chloride ions, while the hydrophilicity increased significantly with time due to the hydrolysis of the ester bonds, which probably contributed to their weak pharmacological activity. The results also showed kinetically hindered aqueous solvation of the halido complexes and low chloride ion affinity of the aqua complexes. The deprotonation of the coordinated aqua ligand in the complexes occurs in the pH = 7-10 range, leading to significant formation (18-30%) of hydroxido species at pH = 7.4. The halido complexes showed somewhat higher cytotoxicity (IC₅₀ = 60-99 μM) on human colon adenocarcinoma cancer cells (Colo205 and Colo320) than the corresponding aqua complexes (IC₅₀ > 100 μM). In all cases, no antibacterial effect was observed (MIC > 100 μM), but some of the complexes showed moderate antiviral activity (IC₅₀ ∼ 50 μM) on Herpes simplex virus 2.