Redox Communication within Multinuclear Iron–Sulfur Complexes Related to Electronic Interplay in the Active Site of [FeFe]Hydrogenase

The one‐electron oxidations of a Fe₂ complex lead to the formation of a persistent metal‐stabilized thiyl radical Fe₂ species, mixed‐valent Fe₄, and Fe₈ complexes. The unpaired spin in the Fe₂ radical species delocalizes over the Fe₂ and the aromatic dithiolate, mostly on the terminal sulfur. The subsequent dimerization of the singly oxidized Fe₂ to the Fe₄ retains the partial thiyl radical character. For an analogue with less steric hindrance, the π–π stacking interaction between the dithiolato aromatic rings induces generation of the Fe₈, in which process electronic structures of the species are modulated through reducing the thiyl radical to the thiolate. Electronic reorganization repeats when the Fe₈ is converted to Fe₄. Electronic interplay in the complexes decreases the energy gap of frontier MOs and buffers electronic impacts upon redox events. Easier accessible redox potentials and increased stability of the species are facilitated. The results demonstrate that electronic versatility of the benzenedithiolate exerts pronounced influences on electronic and coordination structure of the metal complexes.     

In Situ Proteome Profiling and Bioimaging Applications of Small‐Molecule Affinity‐Based Probes Derived From DOT1L Inhibitors

DOT1L is the sole protein methyltransferase that methylates histone H3 on lysine 79 (H3K79), and is a promising drug target against cancers. Small‐molecule inhibitors of DOT1L such as FED1 are potential anti‐cancer agents and useful tools to investigate the biological roles of DOT1L in human diseases. FED1 showed excellent in vitro inhibitory activity against DOT1L, but its cellular effect was relatively poor. In this study, we designed and synthesized photo‐reactive and “clickable” affinity‐based probes (AfBPs), P1 and P2 , which were cell‐permeable and structural mimics of FED1 . The binding and inhibitory effects of these two probes against DOT1L protein were extensively investigated in vitro and in live mammalian cells (in situ). The cellular uptake and sub‐cellular localization properties of the probes were subsequently studied in live‐cell imaging experiments, and our results revealed that, whereas both P1 and P2 readily entered mammalian cells, most of them were not able to reach the cell nucleus where functional DOT1L resides. This offers a plausible explanation for the poor cellular activity of FED1 . Finally with P1 / P2 , large‐scale cell‐based proteome profiling, followed by quantitative LC‐MS/MS, was carried out to identify potential cellular off‐targets of FED1 . Amongst the more than 100 candidate off‐targets identified, NOP2 (a putative ribosomal RNA methyltransferase) was further confirmed to be likely a genuine off‐target of FED1 by preliminary validation experiments including pull‐down/Western blotting (PD/WB) and cellular thermal shift assay (CETSA).     

Close‐Packed Two‐Dimensional Silver Nanoparticle Arrays: Quadrupolar and Dipolar Surface Plasmon Resonance Coupling

Silver nanoparticles (NPs) ranging in size from 40 to 100 nm were prepared in high yield by using an improved seed‐mediated method. The homogeneous Ag NPs were used as building blocks for 2D assembled Ag NP arrays by using an oil/water interface. A close‐packed 2D array of Ag NPs was fabricated by using packing molecules (3‐mercaptopropyltrimethoxysilane) to control the interparticle spacing. The homogeneous 2D Ag NP array exhibited a strong quadrupolar cooperative plasmon mode resonance and a dipolar red‐shift relative to individual Ag NPs suspended in solution. A well‐arranged 2D Ag NP array was embedded in polydimethylsiloxane film and, with biaxial stretching to control the interparticle distance, concomitant variations of the quadrupolar and dipolar couplings were observed. As the interparticle distance increased, the intensity of the quadrupolar cooperative plasmon mode resonance decreased and dipolar coupling completely disappeared. The local electric field of the 2D Ag NP array was calculated by using finite difference time domain simulation and qualitatively showed agreement with the experimental measurements.