Covalent and noncovalent intermediates of an NAD utilizing enzyme, human CD38

Enzymatic utilization of nicotinamide adenine dinucleotide (NAD) has increasingly been shown to have fundamental roles in gene regulation, signal transduction, and protein modification. Many of the processes require the cleavage of the nicotinamide moiety from the substrate and the formation of a reactive intermediate. Using X-ray crystallography, we show that human CD38, an NAD-utilizing enzyme, is capable of catalyzing the cleavage reactions through both covalent and noncovalent intermediates, depending on the substrate used. The covalent intermediate is resistant to further attack by nucleophiles, resulting in mechanism-based enzyme inactivation. The noncovalent intermediate is stabilized mainly through H-bond interactions, but appears to remain reactive. Our structural results favor the proposal of a noncovalent intermediate during normal enzymatic utilization of NAD by human CD38 and provide structural insights into the design of covalent and noncovalent inhibitors targeting NAD-utilization pathways.     

General synthesis of I-III-VI2 ternary semiconductor nanocrystals

Metastable orthorhombic phase of AgInS2 nanocrystals with various shapes, including particles, rods, and worms, have been obtained to demonstrate a facile and effective one-pot chemical route for the synthesis of high quality I-III-VI2 ternary semiconductor nanocrystals (AgInS2, CuInS2, AgInSe2) with controllable shape and size.     

Synthesis and biological investigations of tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC)

We describe the total synthesis and biological properties of a new carboranyl-containing chlorin (TPFC) that might find application as a dual sensitizer in the PDT and BNCT treatment of cancer. TPFC was found to be non-toxic in the dark but showed extensive photosensitizing ability both in vitro and in vivo despite its relatively low singlet oxygen quantum yield. In particular, TPFC exhibited significant photosensitizing activity against highly pigmented melanotic melanoma tumors in mice.     

Phase behavior and properties of reverse vesicles in salt-free catanionic surfactant mixtures

Salt-free 1:1 cationic/anionic (catanionic) surfactant mixture tetradecyltrimethylammonium laurate (TTAL) could be prepared by mixing equimolar tetradecyltrimethylammonium hydroxide (TTAOH) and lauric acid (LA) in water. Given the condition of suitable range of weight fraction of TTAL in total surfactant, rho=WTTAL/(WTTAL+WLA), and at existence of a small amount of water, it was found that the mixtures of so-obtained TTAL and LA could spontaneously form stable reverse vesicles in various organic solvents including toluene, tert-butylbenzene, and cyclohexane. The reverse vesicle phase shows a blue color against room light and exhibits strong birefringence under polarized microscope. The reverse vesicles are very sensitive to temperature change. Increasing temperature could make the rho values within which reverse vesicles were constructed move to higher values. In organic solvents of alkanes such as n-heptane, reverse vesicles could still form but become unstable upon time and centrifugation. Increasing temperature could accelerate phase separation, and finally a gel-like bottom phase was usually observed. Interestingly, the stable reverse vesicles formed by so-called salt-free catanionic surfactant mixtures still show some resistance against adding inorganic salts. They can trap inorganic ions such as Zn2+ and S2- into their hydrophilic layers. This opens the door for template applications of reverse vesicles to prepare inorganic nanoparticles.     

Antimicrobial activity of globulol isolated from the fruits of Eucalyptus globulus Labill

An antimicrobial sesquiterpene was separated by bioassay-guided isolation from the petroleum ether fraction of the ethanol crude extract of Eucalyptus globulus Labill (Myrtaceae) fruits, and was identified as globulol by physicochemical properties and spectroscopic analysis. Mycelial growth method revealed that the median effective inhibitory concentration (IC50) values of globulol on Alternaria solani, Fusarium oxysporum f.sp. niverum, F. graminearum, Rhizoctonia solani and Venturia pirina were 47.1 microg mL(-1), 114.3 microg mL(-1), 53.4 microg mL(-1), 56.9 microg mL(-1), 32.1 microg mL(-1) and 21.8 microg mL(-1), respectively. MTT-colorimetric assay revealed that IC50 values of globulol on Xanthomonas vesicatoria and Bacillus subtilis were 158.0 microg mL(-1) and 737.2 microg mL(-1), respectively. The results indicated that globulol could be a main antimicrobial compound in the ethanol crude extract of E. globulus fruits.     

RCM macrocyclization made practical: an efficient synthesis of HCV protease inhibitor BILN 2061

We report here that dramatic improvement of the key RCM reaction in the synthesis of HCV protease inhibitor BILN2061 can be achieved by N-substitution of the diene substrate with an electron-withdrawing group. Mechanistic studies using 1H NMR spectroscopy showed an unprecedented switch of the initiation sites and the correlation between such switch and the results of RCM, from the unmodified to the modified substrates. We also provided theoretical evidence that such modification may also increase the thermodynamic preference of the macrocyclic product over the diene substrate.     

Multiple-quantum-well perovskite for hole-transport-layer-free light-emitting diodes

We demonstrate hole-transport-layer-free light-emitting diodes(LEDs) based on solution-processed multiple-quantum-well(MQW) perovskite. The MQW perovskite can self-assemble to a unique structure of vertically graded distribution with two-dimensional layered perovskite covered by three-dimensionallike perovskite at top, which can naturally form a barrier of electron transporting to the anode interface,thereby enhancing the charge capture efficiency. This leads to hole-transport-layer-free MQW per...     

Light-guided tumor diagnosis and therapeutics: From nanoclusters to polyoxometalates

Malignant tumors, with the characteristics of easy metastasis and recurrence, are a serious threat to health of mankind. It is urgent to develop promising clinical cancer targeted agents with combination of rapid diagnosis and efficient therapies. Compared with the conventional photosensitizing agents, the recent advances of nanoagents based on transition metal-oxide clusters possess unique structural and electronic properties, greatly improving cancer survival rate, meanwhile, keeping high cont...     

Vesicles of a new salt-free cat-anionic fluoro/hydrocarbon surfactant system

Weakly basic tetradecyldimethylaminoxide (C14DMAO) molecules can be protonated to form a cationic surfactant, C14DMAOH+, by an acidic fluorocarbon surfactant, an 8-2-fluorotelomer unsaturated acid (C7F15CF==CHCOOH), to form a salt-free cationic and anionic (cat-anionic) fluoro/hydrocarbon surfactant system in aqueous solution. The high Krafft point of C7F15CF==CHCOOH was largely reduced as a result of being mixed with a C14DMAO micelle solution. A study of the phase behavior of the new salt-free cat-anionic fluoro/hydrocarbon surfactant system clearly indicates the existence of a birefringent Lalpha-phase region at (25.0+/-0.1) degrees C. The birefringent Lalpha phase consists of vesicles, which include uni- and multilamellar vesicles with one to dozens of shells, and oligovesicular vesicles, as demonstrated by freeze-fracture and cryo-transmission electron microscopy (FF- and cryo-TEM) images. The size distribution and structural transitions in the salt-free cat-anionic fluoro/hydrocarbon surfactant system were studied by dynamic light scattering (DLS) and 1H and 19F NMR spectroscopy. The formation of a salt-free cat-anionic vesicle phase could be induced by the strong electrostatic interaction between the cationic hydrocarbon C14DMAOH+ and the anionic fluorocarbon C7F15CF==CHCOO-, which provided evidence that the electrostatic interaction between the cationic and anionic surfactants is larger than the nonsynergistic interaction between the stiff fluorocarbon and the soft hydrocarbon chains of the surfactants.     

Heat-induced phase transitions from an aqueous solution to precipitates in a poly(sodium 4-styrenesulfonate)/tetradecyltrimethylammonium bromide system

For the first time, temperature-induced phase transitions upon heating and cooling an aqueous solution that contained oppositely charged polyelectrolyte and surfactant mixtures was observed. The phase transition from micelles to vesicles, then to the coexistence of vesicles and superstructures that have the morphology of melon seeds, and finally to precipitates was determined by means of turbidity measurements and transmission electron microscopy images. These phase transitions were shown to be reversible and reproducible after several heating and cooling cycles were performed on the same sample. The novel observations for the temperature-induced phase transition from primary aggregates, such as micelles, to superstructures (i.e., vesicles) should provide new understanding for surfactant sciences, and in particular for self-assembled amphiphilic systems.