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Co( ii ) complexes of 1,4,7,10-tetraazacyclododecane (CYCLEN) or 1,4,8,11-tetraazacyclotetradecane (CYCLAM) with 2-hydroxypropyl or carbamoylmethyl (amide) pendants are studied with the goal of developing paramagnetic chemical exchange saturation transfer (paraCEST) agents. Single-crystal X-ray diffraction studies show that two of the coordination cations with hexadentate ligands, [Co(DHP)] 2+ and [Co(BABC)] 2+ , form six-coordinate complexes; whereas two CYCLEN-based complexes with potentially octadentate ligands, [Co(THP)] 2+ and [Co(HPAC)] 2+ , are seven-coordinate with only three of the four pendant groups bound to the metal center. 1 H NMR spectra of these complexes suggest that the six-coordinate complexes are present as a single isomer in aqueous solution. For the complexes which are seven-coordinate in the solid state, one is highly fluxional in aqueous solution on the NMR time scale ([Co(HPAC)] 2+ ), whereas the NMR spectrum of [Co(THP)] 2+ is consistent with an eight-coordinate complex with all pendants bound. Co( ii ) complexes of CYCLEN derivatives show CEST effects of low intensity that are assigned to NH or OH groups of the pendants. One complex, [Co(DHP)] 2+ , shows a highly-shifted CEST peak at 113 ppm versus bulk water, attributed to OH protons. However, the CEST effect is largest for two Co( ii ) CYCLAM-based complexes with coordinated amide groups that undergo NH proton exchange. All five complexes are inert towards dissociation in buffered solutions containing carbonate and phosphate and towards trans-metalation by excess Zn( ii ). These data give insight into the production of an intense CEST effect for tetraazamacrocyclic complexes with pendant groups containing NH or OH exchangeable protons. The intense and highly shifted CEST peak(s) of the CYCLAM-based complexes suggest that they are promising for further development as paraCEST agents. 

Liposomes containing high-spin Fe(iii ) coordination complexes were prepared towards the production of T 1 MRI probes with improved relaxivity. The amphiphilic Fe( iii) complexes were anchored into the liposome with two alkyl chains to give a coordination sphere containing mixed amide and hydroxypropyl pendant groups. The encapsulated complex contains a macrocyclic ligand with three phosphonate pendants, [Fe(NOTP)] 3−, which was chosen for its good aqueous solubility. Four types of MRI probes were prepared including those with intraliposomal Fe(iii) complex (LipoA) alone, amphiphilic Fe(iii) complex (LipoB), both intraliposomal and amphiphilic complex (LipoC) or micelles formed with amphiphilic complex. Water proton relaxivities r 1 and r 2 were measured and compared to a small molecule macrocyclic Fe(iii) complex containing similar donor groups. Micelles of the amphiphilic Fe( iii) complex had proton relaxivity values ( r 1 = 2.6 mM−1 s −1 ) that were four times higher than the small hydrophilic analog. Liposomes with amphiphilic Fe(iii) complex (LipoB) have a per iron relaxivity of 2.6 mM −1 s −1 at pH 7.2, 34 °C at 1.4 T whereas liposomes containing both amphiphilic and intraliposomal Fe(iii) complexes (lipoC) have r 1 of 0.58 mM −1 s −1 on a per iron basis consistent with quenching of the interior Fe(iii) complex relaxivity. Liposomes containing only encapsulated [Fe(NOTP)]3− have a lowered r 1 of 0.65 mM−1s −1 per iron complex. Studies show that the biodistribution and clearance of the different types liposomal nanoparticles differ greatly. LipoB is a blood pool agent with a long circulation time whereas lipoC is cleared more rapidly through both renal and hepatobiliary pathways. These clearance differences are consistent with lower stability of LipoC compared to LipoB. 

The chemistry of zirconium-based metal-organic polyhedra (ZrMOPs) is often limited by their poor solubilities. Despite their attractive features—including high yielding and facile syntheses, predictable topologies, high stability, and tunability—problematic solubilities have caused ZrMOPs to be under-studied and under-applied. Although these cages have been synthesized with a wide variety of carboxylate-based bridging ligands, we explored a new method for ZrMOP functionalization via node-modification, which we hypothesized could influence solubility. Herein, we report ZrMOPs with benzyl-, vinylbenzyl-, and trifluoromethylbenzyl-pendant groups decorating cyclopentadienyl moieties. The series was characterized by 1 H/ 19 F NMR, high-resolution mass spectrometry, infrared spectroscopy, and single-crystal X-ray diffraction. The effects of node functionalities on ZrMOP solubility were quantified using inductively coupled plasma mass spectrometry. Substitution caused a decrease in water solubility, but for certain organic solvents, e.g. DMF, solubility could be enhanced by ∼20×, from 16 μM for the unfunctionalized cage to 310 μM for the vinylbenzyl- and trifluoromethylbenzyl-cages. 

Self-assembled metallacyles and cages formed via coordination chemistry have been used as catalysts to enforce 4H + /4e − reduction of oxygen to water with an emphasis on attenuating the formation of hydrogen peroxide. That said, the kinetically favored 2H + /2e − reduction to H 2 O 2 is critically important to industry. In this work we report the synthesis, characterization, and electrochemical benchmarking of a hexa-porphyrin cube which catalyses the electrochemical reduction of molecular oxygen to hydrogen peroxide. An established sub-component self-assembly approach was used to synthesize the cubic free-base porphryin topologies from 2-pyridinecarboxaldehyde, tetra-4-aminophenylporphryin (TAPP), and Fe(OTf) 2 (OTf − = trifluoromethansulfonate). Then, a tandem metalation/transmetallation was used to introduce Co( ii ) into the porphyrin faces of the cube, and exchange with the Fe( ii ) cations at the vertices, furnishing a tetrakaideca cobalt cage. Electron paramagnetic resonance studies on a Cu( ii )/Fe( ii ) analogue probed radical interactions which inform on electronic structure. The efficacy and selectivity of the CoCo-cube as a catalyst for hydrogen peroxide generation was investigated using hydrodynamic voltammetry, revealing a higher selectivity than that of a mononuclear Co( ii ) porphyrin (83% versus ∼50%) with orders of magnitude enhancement in standard rate constant ( k s = 2.2 × 10 2 M −1 s −1 versus k s = 3 × 10 0 M −1 s −1 ). This work expands the use of coordination-driven self-assembly beyond ORR to water by exploiting post-synthetic modification and structural control that is associated with this synthetic method. 

ABSTRACT: A metal organic polyhedron (MOP) with four paramagnetic Fe(III) centers was studied as a magnetic reso-nance imaging (MRI) probe. The MOP was characterized in solution by using EPR and UV-vis spectroscopies, FT-ICR mass spectrometry, and in the solid state with single crystal x-ray diffraction. Water proton T1 relaxation properties were examined in solution and showed significant enhancement in the presence of human serum albumin (HSA). The r1 relaxivities in the absence and presence of HSA were 8.7 mM-1s-1 and 21 mM-1s-1, respectively, per molecule (2.2 and 5.3 per Fe) at 4.7 T, 37 °C. In vivo studies of the iron MOP show strong contrast enhancement of blood pool even at a low dose of 0.025 mmol/kg with prolonged residence in vasculature and clearance through the intestinal tract of mice. The MOP binds strongly to serum albumin and shows comparable accumulation in a murine tumor model as a covalently linked Gd-HSA contrast agent.