[Re(CO)3]+ Complexes of exo-Functionalized Tridentate “Click” Macrocycles: Synthesis, Stability, Photophysical Properties, Bioconjugation, and Antibacterial Activity

There is considerable interest in the development of bifunctional ligand scaffolds for the group 7 metals due to potential biological applications. Building on our recent work in the development of “click” ligands and macrocycles, we show that a CuAAC “click” approach can be exploited for the synthesis of a small family of bioconjugated tridentate pyridyl-1,2,3-triazole macrocycles. These bioconjugated tridentate macrocycles form stable [Re­(CO)3]+ complexes, and this could facilitate the development of [M­(CO)3]+ (M = Mn, Tc, Re) targeted agents. The parent macrocycle, bioconjugates, and [Re­(CO)3]+ complexes were characterized by elemental analysis and HR-ESI-MS, 1H and 13C NMR, and IR spectroscopy, and the molecular structures of the alcohol-functionalized macrocycle and two of the Re­(I) complexes were confirmed by X-ray crystallography. The electronic structure of the parent [Re­(CO)3]+ macrocycle complex was examined using UV–vis, Raman, and emission spectroscopy and density functional theory calculations. The complex exhibited intense absorptions in the UV region which were modeled using time-dependent density functional theory (TD-DFT). The calculations suggest that the lower energy part of the absorption band is MLCT in nature and additional higher energy π–π* transitions are present. The complex was weakly emissive at room temperature in methanol with a quantum yield of 5.1 × 10–3 and correspondingly short excited state lifetime (τ ≈ 20 ns). The family of macrocycles and the corresponding Re­(I) complexes were tested for antimicrobial activity in vitro against both Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli) microorganisms. Agar-based disk diffusion assays indicated that two of the Re­(I) complexes displayed antimicrobial activity but the minimum inhibitory concentrations (MIC) for these compounds proved to be extremely modest (MIC > 256 μg/mL).