Copper and Silver Complexes of Tris(triazole)amine and Tris(benzimidazole)amine Ligands: Evidence that Catalysis of an Azide–Alkyne Cycloaddition (“Click”) Reaction by a Silver Tris(triazole)amine Complex Arises from Copper Impurities

The synthesis and characterization of a silver complex of the tripodal triazole ligand, tris­(benzyltriazolylmethyl)­amine (TBTA, <b>L</b>^<b>1</b>), that is used as promoter to enhance Cu^I-catalyzed azide–alkyne cycloaddition (CuAAC) reactions is reported. X-ray analysis of the silver­(I) complex with <b>L</b>¹ reveals a dinuclear cation, [Ag₂(<b>L</b>^<b>1</b>)₂]²⁺, that is essentially isostructural to the copper­(I) analogue. While the [Ag₂(<b>L</b>^<b>1</b>)₂]­(BF₄)₂ complex provides catalysis for the azide–alkyne cycloaddition process, evidence is presented that this arises from trace copper contamination. The synthesis of silver­(I), copper­(II), and copper­(I) complexes of a second tripodal ligand, tris­(2-benzimidazolymethyl)­amine (<b>L</b>^<b>2</b>), which is used to enhance the rate of CuAAC reactions, is also reported. X-ray crystallography of the Cu^I complex [Cu^I₃(<b>L</b>^<b>2</b>)₂(CH₃CN)₂]­(BF₄)₃ offers structural insight into previous mechanistic speculation about the role of this ligand in the CuAAC reaction

[Re(CO)₃]⁺ Complexes of <i>exo</i>-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 <i>in vitro</i> 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)

Toward Hypoxia-Selective Rhenium and Technetium Tricarbonyl Complexes

With the aim of preparing hypoxia-selective imaging and therapeutic agents, technetium­(I) and rhenium­(I) tricarbonyl complexes with pyridylhydrazone, dipyridylamine, and pyridylaminocarboxylate ligands containing nitrobenzyl or nitroimidazole functional groups have been prepared. The rhenium tricarbonyl complexes were synthesized with short reaction times using microwave irradiation. Rhenium tricarbonyl complexes with deprotonated <i>p</i>-nitrophenyl pyridylhydrazone ligands are luminescent, and this has been used to track their uptake in HeLa cells using confocal fluorescent microscopy. Selected rhenium tricarbonyl complexes displayed higher uptake in hypoxic cells when compared to normoxic cells. A ^99mTc tricarbonyl complex with a dipyridylamine ligand bearing a nitroimidazole functional group is stable in human serum and was shown to localize in a human renal cell carcinoma (RCC; SK-RC-52) tumor in a mouse