Structure‐Based Design of Platinum(II) Complexes as c‐myc Oncogene Down‐Regulators and Luminescent Probes for G‐Quadruplex DNA

A series of platinum(II) complexes with tridentate ligands was synthesized and their interactions with G‐quadruplex DNA within the c‐myc gene promoter were evaluated. Complex 1 , which has a flat planar 2,6‐bis(benzimidazol‐2‐yl)pyridine (bzimpy) scaffold, was found to stabilize the c‐myc G‐quadruplex structure in a cell‐free system. An in silico G‐quadruplex DNA model has been constructed for structure‐based virtual screening to develop new Pt^II‐based complexes with superior inhibitory activities. By using complex 1 as the initial structure for hit‐to‐lead optimization, bzimpy and related 2,6‐bis(pyrazol‐3‐yl)pyridine (dPzPy) scaffolds containing amine side‐chains emerge as the top candidates. Six of the top‐scoring complexes were synthesized and their interactions with c‐myc G‐quadruplex DNA have been investigated. The results revealed that all of the complexes have the ability to stabilize the c‐myc G‐quadruplex. Complex 3 a ([Pt^II L2R ] ⁺ ; L2 =2,6‐bis[1‐(3‐piperidinepropyl)‐1H‐enzo[d]imidazol‐2‐yl]pyridine, R =Cl) displayed the strongest inhibition in a cell‐free system (IC₅₀=2.2 μM ) and was 3.3‐fold more potent than that of 1 . Complexes 3 a and 4 a ([Pt^II L3R ]⁺; L3 =2,6‐bis[1‐(3‐morpholinopropyl)‐1H‐pyrazol‐3‐yl]pyridine, R =Cl) were found to effectively inhibit c‐myc gene expression in human hepatocarcinoma cells with IC₅₀ values of ≈17 μM , whereas initial hit 1 displayed no significant effect on gene expression at concentrations up to 50 μM . Complexes 3 a and 4 a have a strong preference for G‐quadruplex DNA over duplex DNA, as revealed by competition dialysis experiments and absorption titration; 3 a and 4 a bind G‐quadruplex DNA with binding constants (K) of approximately 10⁶–10⁷ dm³ mol^?1, which are at least an order of magnitude higher than the K values for duplex DNA. NMR spectroscopic titration experiments and molecular modeling showed that 4 a binds c‐myc G‐quadruplex DNA through an external end‐stacking mode at the 3′‐terminal face of the G‐quadruplex. Intriguingly, binding of c‐myc G‐quadruplex DNA by 3 b is accompanied by an increase of up to 38‐fold in photoluminescence intensity at λ_max=622 nm.     

Enhanced electrochemiluminescence of luminol-O2 system at gold–hydrophobic ionic liquid|water interface

A hydrophobic thiol-functionalized ionic liquid (IL) was synthesized and immobilized tightly on a gold electrode surface via Au–S bond to construct a stable Au–IL|water interface. At the Au–IL|water interface, the electrochemiluminescence (ECL) of luminol-O₂ system was investigated. The ECL intensity of luminol-O₂ system at the Au–IL|water interface was much larger and more stable than that at Au|water interface. The enhanced ECL mechanism at the Au–IL|water interface was studied and discussed in details.     

Thermal explosion simulation and incompatible reaction of dicumyl peroxide by calorimetric technique

Dicumyl peroxide (DCPO) is usually employed as an initiator for polymerization, a source of free radicals, a hardener, and a linking agent. In Asia, due to its unstable reactive nature, DCPO has caused many thermal explosions and runaway reaction incidents in the manufacturing process. This study was conducted to elucidate its essentially thermal hazard characteristics. In order to analyze the runaway behavior of DCPO in a batch reactor, thermokinetic parameters, such as heat of decomposition (ΔH _d) and exothermic onset temperature (T ₀), were measured via differential scanning calorimetry (DSC). Thermal runaway phenomena were then thoroughly investigated by DSC. The thermokinetics of DCPO mixed with acids or bases were determined by DSC, and the experimental data were compared with kinetics-based curve fitting of thermal safety software (TSS). Solid thermal explosion (STE) and liquid thermal explosion (LTE) simulations of TSS were applied to determine the fundamental thermal explosion behavior in large tanks or drums. Results from curve fitting indicated that all of the acids or bases could induce exothermic reactions at even an earlier stage of the experiments. In order to diminish the extent of hazard, hazard information must be provided to the manufacturing process. Thermal hazard of DCPO mixed with nitric acid (HNO₃) was more dangerous than with other acids including sulfuric acid (H₂SO₄), phosphoric acid (H₃PO₄), and hydrochloric acid (HCl). By DSC, T ₀, heat of decomposition (ΔH _d), and activation energy (E _a) of DCPO mixed with HNO₃ were calculated to be 70 °C, 911 J g⁻¹, and 33 kJ mol⁻¹, respectively.     

Complex network structure of musical compositions: Algorithmic generation of appealing music

In this paper we construct networks for music and attempt to compose music artificially. Networks are constructed with nodes and edges corresponding to musical notes and their co-occurring connections. We analyze classical music from Bach, Mozart, Chopin, as well as other types of music such as Chinese pop music. We observe remarkably similar properties in all networks constructed from the selected compositions. We conjecture that preserving the universal network properties is a necessary step in artificial composition of music. Power-law exponents of node degree, node strength and/or edge weight distributions, mean degrees, clustering coefficients, mean geodesic distances, etc. are reported. With the network constructed, music can be composed artificially using a controlled random walk algorithm, which begins with a randomly chosen note and selects the subsequent notes according to a simple set of rules that compares the weights of the edges, weights of the nodes, and/or the degrees of nodes. By generating a large number of compositions, we find that this algorithm generates music which has the necessary qualities to be subjectively judged as appealing.     

H2S-sensing properties of Pt-doped mesoporous indium oxide

Pt-doped mesoporous indium oxide (In₂O₃) has been successfully obtained by a simple and effective in situ nanocasting method. The resultant samples were characterized by XRD, FE-SEM, TEM, N₂ physisorption, XPS and EDX. The gas sensing properties for hydrogen sulfide (H₂S) of the Pt-doped mesoporous In₂O₃ specimens were also examined. The results exhibit those In₂O₃ specimens possess much higher response to H₂S even at low concentration of 2 ppm and a lower optimum working temperature of 150 °C. A possible mechanism was also provided to explain the improvement of the sensing properties.     

Biocatalytic anode for glucose oxidation utilizing carbon nanotubes for direct electron transfer with glucose oxidase

Covalently linked layers of glucose oxidase, single-wall carbon nanotubes and poly-l-lysine on pyrolytic graphite resulted in a stable biofuel cell anode featuring direct electron transfer from the enzyme. Catalytic response observed upon addition of glucose was due to electrochemical oxidation of FADH₂ under aerobic conditions. The electrode potential depended on glucose concentration. This system has essential attributes of an anode in a mediator-free biocatalytic fuel cell.     

Assembly of Nanocrystal Arrays by Block‐Copolymer‐Directed Nucleation

Growing in line: The surface chemistry of self‐assembled nanostructured block copolymers is used to control the sites at which semiconducting metal sulfide nanocrystals nucleate and grow on a surface directly from aqueous solutions. This process is a new and general strategy for the bottom‐up assembly of functional nanocrystalline materials for a variety of applications.

     

Metal Trifluoromethanesulfonate‐Catalyzed Regioselective Reductive Ring Opening of Benzylidene Acetals

A systematic study of various metal trifluoromethanesulfonates as efficient catalysts in the regioselective reductive ring opening of benzylidene acetals is described, including the effects of solvents, reducing agents, and temperature. These catalysts are found to be effective in cleaving the 4,6‐O‐acetal rings of hexopyranosides at either O4 or O6, respectively. When used in conjunction with a 1 M solution of BH₃·THF in THF without extra addition of any solvent, it affects the ring fission at the O6 position to generate the corresponding primary alcohols, whereas O4‐opening takes place in acetonitrile in the presence of dimethylethylsilane as the reductant leading to the secondary hydroxyl derivatives in high selectivity and yields. These methodologies can be applied to a wide range of substrates containing various functional groups.     

Development of a broad toxicological screening technique for urine using ultra-performance liquid chromatography and time-of-flight mass spectrometry

Withdrawal of the support for the REMEDi HS drug profiling system has necessitated its replacement within our laboratories with an alternative broad toxicological screening technique. To this end, a novel method, based on ultra-performance liquid chromatography (UPLC) and time-of-flight (TOF) mass spectrometry, was developed for the routine analysis of urine samples. Identification was achieved by comparison of acquired data to libraries containing more than 300 common drugs and metabolites, and was based on a combination of retention time, exact mass and fragmentation patterns. Validation data for the method is presented and comprised an evaluation of the following parameters: precision; transferability of the methodology between the six collaborating laboratories; specificity; extraction recovery and stability of processed samples; matrix effects and sensitivity.This paper presents the benefits of supplementary fragmentation data with particular regard to increasing specificity and confidence of identification and its usefulness with overdosed samples. The utility of the method was assessed by the parallel analysis of 30 authentic urine samples using the REMEDi HS and UPLC-TOF. The latter provided enhanced detection, leading to the identification of twice as many drugs. Furthermore it did not miss any compounds that were identified by REMEDi HS. The UPLC-TOF findings were further verified by a combination of data from three other conventional screening techniques, i.e., GC-MS, HPLC-DAD and UPLC-MS/MS.