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Deferasirox (Def), an orally administered iron‐chelating drug, has drawn significant interest in repurposing for anticancer application due to the elevated Fe demand by cancer cells. But there are also concerns about its severe off target health effects. Herein Cu(II) binding is studied as a potential off target interaction. The aqueous solution stability and speciation of the ternary complex Cu(Def)(pyridine) was studied by UV‐Vis and EPR spectroscopy, ESI‐mass spectrometry, and cyclic voltammetry under physiologically relevant conditions. The complex is observed to be a redox active, mononuclear Cu(II) complex in square planar geometry. UV‐Vis spectroscopy demonstrates that at pH 7.4 the complex is quite stable (ϵ337nm =10,820 M^−1cm^−1) with a log K=16.65±0.1. Cu scavenging from the Cu transporters ceruloplasmin and albumin was also studied. Def does not inhibit ceruloplasmin activity but forms a ternary Cu(II) complex at the bovine serum albumin ATCUN site. Cu(Def)(py) displays potent but nonselective cytotoxicity against A549 cancer and MRC‐5 noncancer lung cells but the potency of the ternary protein complex was more moderate. This work elucidates potential Def toxicity from Cu complexation in the body but also cytotoxic synergy between the metal and chelator that informs on new drug design directions. 

Biopyrrin pigments, which result from the degradation of heme in biological settings, feature three or two pyrrole rings and characteristic pyrrolin-2-one termini. These scaffolds serve as redox-active ligands and electron reservoirs in coordination compounds. Tripyrrin-1,14-dione coordinates divalent transition metals as a dianionic ligand hosting a delocalized radical. Herein, we report the synthesis and characterization of palladium(II) and platinum(II) tripyrrindione complexes featuring a primary amine (i.e., aniline, tert-butylamine, 1,2-ethylenediamine) at the fourth coordination site within square planar geometries. Interligand hydrogen-bonding interactions are observed between the coordinated amine and the carbonyl groups on the tripyrrindione scaffold. Notably, 1,2-ethylenediamine is employed to link two Pt(II) tripyrrindione complexes. As revealed by optical absorption and electron paramagnetic resonance (EPR) spectroscopy, all resulting complexes present ligand-based radicals that are stable at room temperature and when exposed to air. Spin pairing through multicenter interactions leads to [Formula: see text]-dimerization of the tripyrrindione radicals and a decrease in the EPR signal at low temperatures. Electrochemical measurements indicate that the ligand system undergoes quasi-reversible one-electron oxidation and reduction, thus confirming the ability of tripyrrindione to form square planar complexes in three different redox states. 

The tripyrrin-1,14-dione biopyrrin, which shares the scaffold of several naturally occurring heme metabolites, is a redox-active platform for metal coordination. We report the synthesis of square planar platinum( ii ) tripyrrindiones, in which the biopyrrin binds as a tridentate radical and the fourth coordination position is occupied by either aqua or tert -butyl isocyanide ligands. These complexes are stable through chromatographic purification and exposure to air. Electron paramagnetic resonance (EPR) data and density functional theory (DFT) analysis confirm that the spin density is located predominantly on the tripyrrindione ligand. Pancake bonding in solution between the Pt( ii ) tripyrrindione radicals leads to the formation of diamagnetic π dimers at low temperatures. The identity of the monodentate ligand ( i.e. , aqua vs . isocyanide) affects both the thermodynamic parameters of dimerization and the tripyrrindione-based redox processes in these complexes. Isolation and structural characterization of the oxidized complexes revealed stacking of the diamagnetic tripyrrindiones in the solid state as well as a metallophilic Pt( ii )−Pt( ii ) contact in the case of the aqua complex. Overall, the properties of Pt( ii ) tripyrrindiones, including redox potentials and intermolecular interactions in solution and in the solid state, are modulated through easily accessible changes in the redox state of the biopyrrin ligand or the nature of the monodentate ligand. 

Low molecular weight hydrogels are made of small molecules that aggregate via noncovalent interactions. Here, comprehensive characterization of the physical and chemical properties of hydrogels made from thioglycolipids of the disaccharides lactose and cellobiose with simple alkyl chains is reported. While thiolactoside hydrogels are robust, thiocellobioside gels are metastable, precipitating over time into fibrous crystals that can be entangled to create pseudo-hydrogels. Rheology confirms the viscoelastic solid nature of these hydrogels with storage moduli ranging from 10–600 kPa. Additionally, thiolactoside hydrogels are thixotropic which is a desirable property for many potential applications. Freeze-fracture electron microscopy of xerogels shows layers of stacked sheets that are entangled into networks. These structures are unique compared to the fibers or ribbons typically reported for hydrogels. Differential scanning calorimetry provides gel-to-liquid phase transition temperatures ranging from 30 to 80 °C. Prodan fluorescence spectroscopy allows assignment of phase transitions in the gels and other lyotropic phases of high concentration samples. Phase diagrams are estimated for all hydrogels at 1–10 wt% from 5 to ≥ 80 °C. These hydrogels represent a series of interesting materials with unique properties that make them attractive for numerous potential applications.