ABSTRACT
The preparation of three new heterometallic clusters [Ce6Mn12O17(O2CPh)26] (1), [Ce10Mn14O24(O2CPh)32] (2), and [Ce23Mn20O48(OH)2(tbb)46(H2O)4](NO3)2 (3; tbb- = 4-tBu-benzoate) is reported. They all possess unprecedented structures with a common feature being the presence of an octahedral CeIV-oxo core: a Ce6 in 1, two edge-fused Ce6 giving a Ce10 bioctahedron in 2, or a larger Ce19 octahedron in 3. Complex 1 is the first Ce6 cluster with a central µ6-O2-. 2 and the cation of 3 are molecular nanoparticles of CeO2 (ceria) because they possess the fluorite structure of bulk ceria and are thus ultrasmall ceria nanoparticles in molecular form. The {Ce19O32} octahedral subunit of the cation of 3 had been predicted from density functional theory studies to be one of the stable fragments of the CeO2 lattice, but has never been previously synthesized in molecular chemistry. Around the Ce/O core of 1-3 is an incomplete monolayer of Mnn ions disposed as four Mn3, two Mn7, and four Mn5 units, respectively. This represents a clear structural similarity with composite (phase-separated) CeO2/MnOx mixtures where at high Ce:Mn ratios the Mn atoms segregate on the surface of CeO2 phases. Variable-temperature dc and ac magnetic susceptibility studies have revealed S = 2, S = 1/2, and S = 3/2 ground states for 1-3, respectively. Fitting of the 5.0-300 K dc data for 1 to a two-J model for an asymmetrical V-shaped Mn3 unit with no interaction between the end MnIII ions gave an excellent fit with the following values: J1 = 5.2(3) cm-1, J2 = -7.4(3) cm-1, and g = 1.96(2).
ABSTRACT
The Ebola virus (EBOV) causes severe human infection that lacks effective treatment. A recent screen identified a series of compounds that block EBOV-like particle entry into human cells. Using data from this screen, quantitative structure-activity relationship models were built and employed for virtual screening of a â¼17 million compound library. Experimental testing of 102 hits yielded 14 compounds with IC50 values under 10 µM, including several sub-micromolar inhibitors, and more than 10-fold selectivity against host cytotoxicity. These confirmed hits include FDA-approved drugs and clinical candidates with non-antiviral indications, as well as compounds with novel scaffolds and no previously known bioactivity. Five selected hits inhibited BSL-4 live-EBOV infection in a dose-dependent manner, including vindesine (0.34 µM). Additional studies of these novel anti-EBOV compounds revealed their mechanisms of action, including the inhibition of NPC1 protein, cathepsin B/L, and lysosomal function. Compounds identified in this study are among the most potent and well-characterized anti-EBOV inhibitors reported to date.
