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

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posted on 22.12.2014 by Asif Noor, Gregory S. Huff, Sreedhar V. Kumar, James E. M. Lewis, Brett M. Paterson, Christine Schieber, Paul S. Donnelly, Heather J. L. Brooks, Keith C. Gordon, Stephen C. Moratti, James D. Crowley
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).