We report the formation of one- and two-dimensional metal–organic coordination structures from para-hexaphenyl-dicarbonitrile (NC–Ph6–CN) molecules and Cu atoms on graphene epitaxially grown on Ir(111). By varying the stoichiometry between the NC–Ph6–CN molecules and Cu atoms, the dimensionality of the metal–organic coordination structures could be tuned: for a 3:2 ratio, a two-dimensional hexagonal porous network based on threefold Cu coordination was observed, while for a 1:1 ratio, one-dimensional chains based on twofold Cu coordination were formed. The formation of metal–ligand bonds was supported by imaging the Cu atoms within the metal–organic coordination structures with scanning tunneling microscopy. Scanning tunneling spectroscopy measurements demonstrated that the electronic properties of NC–Ph6–CN molecules and Cu atoms were different between the two-dimensional porous network and one-dimensional molecular chains.

Macrophage migration inhibitory factor (MIF) is a cytokine with key roles in inflammation and cancer, which qualifies it as a potential drug target. Apart from its cytokine activity, MIF also harbors enzyme activity for keto–enol tautomerization. MIF enzymatic activity has been used for identification of MIF binding molecules that also interfere with its biological activity. However, MIF tautomerase activity assays are troubled by irregularities, thus creating a need for alternative methods. In this study, we identified a 7-hydroxycoumarin fluorophore with high affinity for the MIF tautomerase active site ( K i = 18 ± 1 nM) that binds with concomitant quenching of its fluorescence. This property enabled development of a novel competition-based assay format to quantify MIF binding. We also demonstrated that the 7-hydroxycoumarin fluorophore interfered with the MIF–CD74 interaction and inhibited proliferation of A549 cells. Thus, we provide a high-affinity MIF binder as a novel tool to advance MIF-oriented research.

In the present manuscript, we describe how we successfully used ligand-based virtual screening (LBVS) to identify two small-molecule, drug-like hit classes with excellent ADMET profiles against the difficult to address...

Linking of reactive groups and ligands by imine chemistry provides chemical probes that label proteins of interest.

Various mechanisms for regulated cell death include the formation of oxidative mediators such as lipid peroxides and nitric oxide (NO). In this respect, 15-lipoxygenase-1 (15-LOX-1) is a key enzyme that catalyzes the formation of lipid peroxides. The actions of these peroxides are interconnected with nuclear factor-κB signaling and NO production. Inhibition of 15-LOX-1 holds promise to interfere with regulated cell death in inflammatory conditions. In this study, a novel potent 15-LOX-1 inhibitor, 9c (i472), was developed and structure–activity relationships were explored. In vitro, this inhibitor protected cells from lipopolysaccharide-induced cell death, inhibiting NO formation and lipid peroxidation. Thus, we provide a novel 15-LOX-1 inhibitor that inhibits cellular NO production and lipid peroxidation, which set the stage for further exploration of these mechanisms.