Mechanism‐Guided Design and Synthesis of a Mitochondria‐Targeting Artemisinin Analogue with Enhanced Anticancer Activity

Understanding the mechanism of action (MOA) of bioactive natural products will guide endeavor to improve their cellular activities. Artemisinin and its derivatives inhibit cancer cell proliferation, yet with much lower efficiencies than their roles in killing malaria parasites. To improve their efficacies on cancer cells, we studied the MOA of artemisinin using chemical proteomics and found that free heme could directly activate artemisinin. We then designed and synthesized a derivative, ART‐TPP, which is capable of targeting the drug to mitochondria where free heme is synthesized. Remarkably, ART‐TPP exerted more potent inhibition than its parent compound to cancer cells. A clickable probe ART‐TPP‐Alk was also employed to confirm that the attachment of the TPP group could label more mitochondrial proteins than that for the ART derivative without TPP (AP1). This work shows the importance of MOA study, which enables us to optimize the design of natural drug analogues to improve their biological activities.     

Novel microchip for in situ TEM imaging of living organisms and bio-reactions in aqueous conditions

A novel and disposable microchip (K-kit) with SiO(2) nano-membranes was developed and used as a specimen kit for in situ imaging of living organisms in an aqueous condition using transmission electron microscopy (TEM) without equipment modification. This K-kit enabled the successful TEM observation of living Escherichia coli cells and the tellurite reduction process in Klebsiella pneumoniae. The K. pneumoniae and Saccharomyces cerevisiae can stay alive in K-kit after continuous TEM imaging for up to 14 s and 42 s, respectively. Besides, different tellurite reduction profiles in cells grown in aerobic and anaerobic environments can be clearly revealed. These results demonstrate that the K-kit developed in this paper can be useful for observing living organisms and monitoring biological processes in situ.     

Novel polymer composite to eliminate background matrix ions in matrix assisted laser desorption/ionization-mass spectrometry

Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) is rarely used for the analysis of small molecules (< 700 Da) because the low m/z signal is overwhelmed by a high background of matrix ions. We have developed a solution to this problem that employs a novel polymer composite which is formed by covalently cross-linking alpha-cyano-4-hydroxycinnamic acid (HCCA) to SU-8 photoresist via cationic photo-polymerization. Since the HCCA molecules are immobilized, background noise resulting from the matrix ions is significantly reduced or eliminated. Moreover, owing to the hydrophobic surface of the polymer film, the sample spots shrink during solvent evaporation and thus the analytes can be concentrated. As a result, this polymer composite improves detection sensitivity and extends the analyzable species to the low-mass region. The covalent incorporation of HCCA with SU-8 was validated with reflectance FTIR spectroscopy, and the polymer surface was characterized with scanning electron microscopy (SEM). Using MRFA, a small peptide as a standard, 8 mg of HCCA per mL of SU-8 photoresist was found to yield the highest sensitivity and the lowest background noise. Analytes such as peptides or small organic molecules were further examined on this composite surface and no analyte degradation was observed. In a trial of peptide mass fingerprinting of cytochrome c on the composite substrate, the inclusion of low m/z tryptic peptides in the database search dramatically improved the protein identification probability score.     

Benchmark values of Shannon entropy for spherically confined hydrogen atom

The information‐theoretic measure of confined hydrogen atom has been investigated extensively in the literature. However, most of them were focused on the ground state and accurate values of information entropies, such as Shannon entropy, for confined hydrogen are still not determined. In this work, we establish the benchmark results of the Shannon entropy for confined hydrogen atom in a spherical impenetrable sphere, in both position and momentum spaces. This is done by examining the bound state energies, the normalization of wave functions, and the scaling property with respect to isoelectronic hydrogenic ions. The angular and radial parts of Shannon entropy in two conjugate spaces are provided in detail for both free and confined hydrogen atom in ground and several excited states. The entropies in position space decrease logarithmically with decreasing the size of confinement, while those in momentum space increase logarithmically. The Shannon entropy sum, however, approaches to finite values when the confinement radius closes to zero. It is also found that the Shannon entropy sum shares same trend for states with similar density distributions. Variations of entropy for nodeless bound states are significantly distinct form those owning nodes when changing the confinement radius.     

Quantification of Linear Entropy for Quantum Entanglement in He, H− and Ps− Ions Using Highly-Correlated Hylleraas Functions

The quantum entanglement for the two electrons in three-body atomic systems such as the helium atom, the hydrogen negative ion and the positronium negative ion are investigated by employing highly correlated Hylleraas functions to represent the ground states of such systems. As a measure of the spatial entanglement, the linear entropy of the reduced density matrix is calculated for the ground states. The required four-electron (12-dimensional) integrals are solved analytically such that they are suitable for machine computations. Results are compared with other calculations when available.     

Water absorption and enzymatic degradation of poly(lactic acid)/rice starch composites

Poly(lactic acid) (PLA) composites consisting of PLA, rice starch (RS) (0–50 wt%) and epoxidised natural rubber (ENR50) were compounded by a twin-screw extruder and compression moulded into dumbbell specimens. Tensile tests were performed to characterize the mechanical properties of the PLA/RS composites. Morphological studies were done on the tensile fractured surface of the specimens by using scanning electron microscopy (SEM). Twenty weight percent of RS achieved a good balance of strength and stiffness. Beyond 20 wt% loading of RS, the tensile strength and elongation at break of PLA decreased drastically. This may be attributed to the agglomeration of RS, which could then act as stress concentrator. The incorporation of ENR50 increased the tensile strength and elongation at break of the PLA/RS composites remarkably, owing to the elastomeric behaviour and compatibilisation effects of ENR50. Interestingly, the morphology of PLA/RS composites transformed to a more ductile one with the addition of ENR. The kinetics of water absorption of the PLA/RS composites conforms to Fick's law. The M_m and D values are dependent on the RS and ENR concentrations. The tensile properties of the PLA/RS composites deteriorated after water absorption. The retention-ability and recoverability of the PLA/RS composites are relatively low, attributed to the hydrolysis of PLA, degradation of the PLA–RS interface and leaching of the RS particles. In addition, the tensile properties of PLA/RS composites decreased drastically upon exposure to enzymatic degradation. Extensive pinhole and surface erosion on the PLA/RS composites indicate high degree of hydrolysis. Whilst the addition of ENR leads to some improvements in tensile properties, nevertheless, it enhanced the biodegradability of the PLA/RS composites when exposed to water and -amylase enzymatic treatments.     

upper bond 1 start]PdCl[PPh(2)CH(2)CH(2)C[upper bond 1 end]HCH(2)CH(2)PPh(2)] as a precursor to homo- and hetero-metallic species directed by ESMS (electrospray ionisation mass spectrometry)

The cyclometallated Pd compound [upper bond 1 start]PdCl[PPh(2)CH(2)CH(2)C[upper bond 1 end]HCH(2)CH(2)PPh(2)], obtained from PdCl(2)(Ph(2)P(CH(2))(5)PPh(2)) in refluxing DMF (N,N-dimethylformamide), was characterized by NMR and X-ray single-crystal diffraction analysis. The cyclometallation of MCl(2)(Ph(2)P(CH(2))(5)PPh(2))(M = Pd, Pt) to give and its Pt(ii) analogue was probed using electrospray ionisation mass spectrometry (ESMS). The reactivity of towards neutral ligands such as phosphines and pyridines as well as basic metal complexes such as pyridine-thiolate compounds of Au(i), Hg(ii) and Pt(ii) in solution was also investigated. The results showed that the chloride trans to the Pd-C bond is susceptible to ligand replacement. A number of entry metalloligands was examined in an attempt to establish a route to cyclometallated aggregates and clusters.     

Electrochemistry of Layered Graphitic Carbon Nitride Synthesised from Various Precursors: Searching for Catalytic Effects

Graphitic carbon nitride (g‐C₃N₄), synthesised by pyrolysis of different precursors (dicyandiamide, melamine and urea) under varying reaction conditions (air and nitrogen gas) is subjected to electrochemical studies for the elucidation of the inherent catalytic efficiency of the pristine material. Contrary to popular belief, pristine g‐C₃N₄ shows negligible, if any, enhancement in its electrochemical behaviour in this comprehensive study. Voltammetric analysis reveals g‐C₃N₄ to display similar catalytic efficiency to the unmodified glassy carbon electrode surface on which the bulk material was deposited. This highlights the non‐catalytic nature of the pristine material and challenges the feasibility of using g‐C₃N₄ as a heterogeneous catalyst to deliver numerous promised applications.     

Revisiting the generalized pseudospectral method: Radial expectation values,fine structure,and hyperfine splitting of confined atom

This paper revisits the generalized pseudospectral (GPS) method on the calculation of various radial expectation values of atomic systems, especially on the spatially confined hydrogen atom and harmonic oscillator. As one of the collocation methods based on global functions, the powerfulness and robustness of the GPS method has been well established in solving the radial Schrödinger equation with high accuracy. However, in our recent work, it was found that the previous calculations based on the GPS method for the radial expectation values of confined systems show significant discrepancies with other theoretical methods. In this work we have tackled such a problem by tracing its source to the GPS method and found that the method itself may not be able to obtain the system wave function at the origin. Combined with an extrapolation method developed here, the GPS method can fully reproduce the radial quantities obtained by other theoretical methods, but with more flexibility, efficiency, and accuracy. We apply the GPS-extrapolation method to investigate the relatievistic fine structure and hyperfine splitting of confined hydrogen atom in s-wave states where the zero-point wave function dominates. Good agreement with previous predictions is obtained for confined hydrogen in low-lying states, and benchmark results are obtained for high-lying excited states. The perturbation treatment of the fine and hyperfine interactions is validated in the confining environment.     

Completely p-summing maps on the operator Hilbert space OH

We prove the completely p-summing ideals of OH are all equal as sets for 1?p<2. A phase transition then occurs at p=2 as we also show for p?2, the completely p-summing ideals of OH turn out as sets to be Schatten ideal classes with the limiting case being the Schatten 4-class ideal S₄ when p→∞.