Discrete Hf18 Metal-oxo Cluster as a Heterogeneous Nanozyme for Site-Specific Proteolysis

The selective hydrolysis of proteins by non-enzymatic catalysis is difficult to achieve, yet it is crucial for applications in biotechnology and proteomics. Herein, we report that discrete hafnium metal-oxo cluster [Hf₁₈O₁₀(OH)₂₆(SO₄)₁₃⋅(H₂O)₃₃] ( Hf₁₈ ), which is centred by the same hexamer motif found in many MOFs, acts as a heterogeneous catalyst for the efficient hydrolysis of horse heart myoglobin (HHM) in low buffer concentrations. Among 154 amino acids present in the sequence of HHM, strictly selective cleavage at only 6 solvent accessible aspartate residues was observed. Mechanistic experiments suggest that the hydrolytic activity is likely derived from the actuation of Hf^IV Lewis acidic sites and the Brønsted acidic surface of Hf₁₈ . X-ray scattering and ESI-MS revealed that Hf₁₈ is completely insoluble in these conditions, confirming the HHM hydrolysis is caused by a heterogeneous reaction of the solid Hf₁₈ cluster, and not from smaller, soluble Hf species that could leach into solution.     

Target Design of Novel Histone Deacetylase 6 Selective Inhibitors with 2-Mercaptoquinazolinone as the Cap Moiety

Epigenetic alterations found in all human cancers are promising targets for anticancer therapy. In this sense, histone deacetylase inhibitors (HDACIs) are interesting anticancer agents that play an important role in the epigenetic regulation of cancer cells. Here, we report 15 novel hydroxamic acid-based histone deacetylase inhibitors with quinazolinone core structures. Five compounds exhibited antiproliferative activity with IC₅₀ values of 3.4–37.8 µM. Compound 8 with a 2-mercaptoquinazolinone cap moiety displayed the highest antiproliferative efficacy against MCF-7 cells. For the HDAC6 target selectivity study, compound 8 displayed an IC₅₀ value of 2.3 µM, which is 29.3 times higher than those of HDAC3, HDAC4, HDAC8, and HDAC11. Western blot assay proved that compound 8 strongly inhibited tubulin acetylation, a substrate of HDAC6. Compound 8 also displayed stronger inhibition activity against HDAC11 than the control drug Belinostat. The inhibitory mechanism of action of compound 8 on HDAC enzymes was then explored using molecular docking study. The data revealed a high binding affinity (−7.92 kcal/mol) of compound 8 toward HDAC6. In addition, dock pose analysis also proved that compound 8 might serve as a potent inhibitor of HDAC11.     

The Groups of Symmetric Genus σ ≤ 8

Let G be a finite group. The symmetric genus σ (G) is the minimum genus of any compact Riemann surface on which G acts faithfully as a group of automorphisms. Here we classify the groups of symmetric genus σ, for all values of σ such that 4 ≤ σ ≤ 8. In addition, we obtain some general results about the partial presentations that groups acting on surfaces must have. We show that a group with even genus and no “large order” elements in its Sylow 2-subgroup has restrictions on its Sylow 2-subgroup. As a consequence, we show that if G is a 2-group with positive symmetric genus, then σ(G) is odd. The software package MAGMA was employed to help with the calculations, and the MAGMA library of small groups was essential to the classification.     

Self‐Assembly of Uranyl–Peroxide Nanocapsules in Basic Peroxidic Environments

A wide range of uranyl–peroxide nanocapsules have been synthesized using very simple reactants in basic media; however, little is known about the process to form these species. We have performed a density functional theory study of the speciation of the uranyl ions under different experimental conditions and explored the formation of dimeric species via a ligand exchange mechanism. We shed some light onto the importance of the excess of peroxide and alkali counterions as a thermodynamic driving force towards the formation of larger uranyl–peroxide species.     

Rapid initiation of reactions in Al/Ni multilayers with nanoscale layering

Research into nanoenergetic materials is enabling new capabilities for controlling exothermic reaction rates and energy output, as well as new methods for integrating these materials with conventional electronics fabrication techniques. Many reactions produce primarily heat, and in some cases it is desirable to increase the rate of heat release beyond what is typically observed. Here we investigate the Al-Ni intermetallic reaction, which normally propagates across films or foils at rates lower than 10 m/s. However, models and experiments indicate that local heating rates can be very high (10⁷ K/s), and uniform heating of such a multilayer film can lead to a rapid, thermally explosive type of reaction. With the hopes of using a device to transduce electrical energy to kinetic energy of a flyer plate in the timescale of 100's of nanoseconds, we have incorporated a Ni/Al nanolayer film that locally heats upon application of a large electrical current. We observed flyer plate velocities in the 2-6 km/s range, corresponding to 4-36 kJ/g in terms of specific kinetic energy. Several samples containing Ni/Al films with different bilayer thicknesses were tested, and many produced additional kinetic energy in the 1.1-2.3 kJ/g range, as would be expected from the Ni-Al intermetallic reaction. These results provide evidence that nanoscale Ni/Al layers reacted in the timescale necessary to contribute to device output.     

The Key Role of U28 in the Aqueous Self‐Assembly of Uranyl Peroxide Nanocages

For 11 years now, the structural diversity and aesthetic beauty of uranyl–peroxide capsules have fascinated researchers from the diverse fields of mineralogy, polyoxometalate chemistry, and nuclear fuel technologies. There is still much to be learned about the mechanisms of the self‐assembly process, and the role of solution parameters including pH, alkali template, temperature, time, and others. Here we have exploited the high solubility of the UO₂²⁺/H₂O₂/LiOH aqueous system to address the effect of the hydroxide concentration. Important techniques of this study are single‐crystal X‐ray diffraction, small‐angle X‐ray scattering, and Raman spectroscopy. Three key phases dominate the solution speciation as a function of time and the LiOH/UO₂²⁺ ratio: the uranyl–triperoxide monomer [UO₂(O₂)₃]^4?and the two capsules [(UO₂)(O₂)(OH)]₂₄^24?(U₂₄) and [(UO₂)(O₂)_1.5]₂₈^28?(U₂₈). When the LiOH/U ratio is around three, U₂₈ forms rapidly and this cluster can be isolated in high yield and purity. This result was most surprising and challenges the hypothesis that alkali templating is the most important determinant in the cluster geometry. Moreover, analogous experiments with KOH, NH₄OH, and TEAOH (TEA=tetraethylammonium) also rapidly yield U₂₈, which suggests that U₂₈ is the kinetically favored species. Complete mapping of the pH–time phase space reveals only a narrow window of the U₂₈ dominance, which is why it was previously overlooked as an important kinetic species in this chemical system, as well as others with different counterions.     

On the cohomology of generalized homogeneous spaces

We observe that work of Gugenheim and May on the cohomology of classical homogeneous spaces of Lie groups applies verbatim to the calculation of the cohomology of generalized homogeneous spaces , where is a finite loop space or a -compact group and is a ``subgroup' in the homotopical sense.