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

Abstract

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).

Rhenium Complexes Based on an N2O Tridentate Click Scaffold: From Synthesis, Structural and Theoretical Characterization to a Radiolabelling Study

“…Both five‐membered chelate rings are strongly distorted. The Re–CO and Re–N bond lengths (see Table ) are consistent with the values reported for related Re I –tricarbonyl complexes, especially those incorporating tridentate triazolyl‐based ligands , , . The crystal‐packing analysis demonstrated that the crystal structures of [Re(CO) 3 ( 5 –H )] and [Re(CO) 3 ( 11 –H )] are stabilized by an intricate network involving N–H ··· O hydrogen bonds and weak intermolecular C–H ··· O and C–H ··· N interactions (see Table S1.1 in part 1 of the Supporting Information).…”

Recent Studies on the Antimicrobial Activity of Transition Metal Complexes of Groups 6–12

“…In 2014, Noor et al described a family of bioconjugated tridentate pyridyl-1,2,3-triazole macrocycles and the corresponding rhenium(I) complexes (21, Figure 5), which were screened for antimicrobial activities in vitro against both Gram-positive (S. aureus) and Gram-negative (E. coli) bacterial strains [72]. The minimum inhibitory concentrations for the compounds, however, showed values >256 µg/mL.…”

Design, synthesis and in vivo evaluation of 3-arylcoumarin derivatives of rhenium(I) tricarbonyl complexes as potent antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA)

“…Some of these molecules demonstrated activity in the low micromolar or even nanomolar range with no cytotoxicity or hemolytic activity at much higher concentrations [20,24]. Interestingly, rhenium complexes, mostly explored for their anti-tumor properties, were recently shown to possess promising antibacterial potency [35][36][37][38][39][40][41]. In particular, Wenzel, Patra et al introduced a trimetallic complex comprised of a ferrocenyl (Fc), a cymantrene and a [(dpa)Re(CO)s] residue (dpa = N,N-bis(pyridine-2ylmethyl)prop-2-yn-1-amine) as the main biological active moiety of the construct [36,37].…”